{"id":26992,"date":"2024-01-03T21:41:02","date_gmt":"2024-01-03T19:41:02","guid":{"rendered":"https:\/\/hho-bulgaria.com\/h2-gas-reduces-neurologic-injury-in-circulatory-arrest\/"},"modified":"2024-01-29T21:14:09","modified_gmt":"2024-01-29T19:14:09","slug":"h2-gas-reduces-neurologic-injury-in-circulatory-arrest","status":"publish","type":"post","link":"https:\/\/hho-bulgaria.com\/en\/h2-gas-reduces-neurologic-injury-in-circulatory-arrest\/","title":{"rendered":"H2 Gas Reduces Neurologic Injury in Circulatory Arrest"},"content":{"rendered":"<div class=\"jig-ncbiinpagenav\" data-jigconfig=\"smoothScroll: false, allHeadingLevels: ['h2'], headingExclude: ':hidden,.nomenu'\" id=\"ui-ncbiinpagenav-1\">\n<div class=\"fm-sec half_rhythm no_top_margin\">\n<div class=\"fm-flexbox\">\n<div class=\"fm-citation\">\n<div class=\"citation-default\">\n<div class=\"part1\"><span role=\"menubar\"><a href=\"#\" role=\"menuitem\" aria-expanded=\"false\" aria-haspopup=\"true\">JACC Basic Transl Sci.<\/a><\/span> 2019 Apr; 4(2): 176\u2013187. <\/div>\n<div class=\"part2\"><span class=\"fm-vol-iss-date\">Published online 2019 Mar 27. <\/span>  <span class=\"doi\"><span>doi:&nbsp;<\/span><a href=\"\/\/doi.org\/10.1016%2Fj.jacbts.2018.11.006\" target=\"_blank\" rel=\"noopener noreferrer\" ref=\"reftype=other&amp;article-id=6488769&amp;issue-id=333532&amp;journal-id=3485&amp;FROM=Article%7CFront%20Matter&amp;TO=Content%20Provider%7CCrosslink%7CDOI\">10.1016\/j.jacbts.2018.11.006<\/a><\/span><\/div>\n<\/div>\n<\/div>\n<div class=\"fm-ids\">\n<div class=\"fm-citation-pmcid\"><span class=\"fm-citation-ids-label\">PMCID: <\/span><span>PMC6488769<\/span><\/div>\n<div class=\"fm-citation-pmid\">PMID: <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/31061920\">31061920<\/a><\/div>\n<\/div>\n<\/div>\n<h1 class=\"content-title\">Perioperatively Inhaled Hydrogen Gas Diminishes Neurologic Injury Following Experimental Circulatory Arrest in Swine<\/h1>\n<div class=\"half_rhythm\">\n<div class=\"contrib-group fm-author\"><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Cole%20AR%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427036931120\" co-class=\"co-affbox\">Alexis R. Cole<\/a>, BS,<sup>a<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Perry%20DA%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427034232976\" co-class=\"co-affbox\">Dorothy A. Perry<\/a>, MBChB,<sup>a,<\/sup><sup>b<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Raza%20A%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427039082592\" co-class=\"co-affbox\">Ali Raza<\/a>, MD,<sup>a,<\/sup><sup>b<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Nedder%20AP%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427038110528\" co-class=\"co-affbox\">Arthur P. Nedder<\/a>, DVM,<sup>c<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Pollack%20E%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427040062864\" co-class=\"co-affbox\">Elizabeth Pollack<\/a>, DVM Candidate,<sup>c<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Regan%20WL%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427040060624\" co-class=\"co-affbox\">William L. Regan<\/a>, CCP, LP,<sup>d<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=van%20den%20Bosch%20SJ%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427039634064\" co-class=\"co-affbox\">Sarah J. van den Bosch<\/a>, MS,<sup>a<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Polizzotti%20BD%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427011236000\" co-class=\"co-affbox\">Brian D. Polizzotti<\/a>, PhD,<sup>a,<\/sup><sup>b<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Yang%20E%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427039318224\" co-class=\"co-affbox\">Edward Yang<\/a>, MD,<sup>e,<\/sup><sup>f<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Davila%20D%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427012209456\" co-class=\"co-affbox\">Daniel Davila<\/a>, MD,<sup>g,<\/sup><sup>h<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Afacan%20O%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427027201680\" co-class=\"co-affbox\">Onur Afacan<\/a>, MD,<sup>e,<\/sup><sup>f<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Warfield%20SK%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427036188768\" co-class=\"co-affbox\">Simon K. Warfield<\/a>, PhD,<sup>e,<\/sup><sup>f<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Ou%20Y%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427035936096\" co-class=\"co-affbox\">Yangming Ou<\/a>, PhD,<sup>b,<\/sup><sup>e,<\/sup><sup>f<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Sefton%20B%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427041200320\" co-class=\"co-affbox\">Brenda Sefton<\/a>, PA,<sup>d<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Everett%20AD%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427082225696\" co-class=\"co-affbox\">Allen D. Everett<\/a>, MD,<sup>i<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Neil%20JJ%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427023452368\" co-class=\"co-affbox\">Jeffrey J. Neil<\/a>, MD, PhD,<sup>e,<\/sup><sup>f<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Lidov%20HG%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427039650608\" co-class=\"co-affbox\">Hart G.W. Lidov<\/a>, MD, PhD,<sup>h,<\/sup><sup>j,<\/sup><sup>k<\/sup> <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Mayer%20JE%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427040984208\" co-class=\"co-affbox\">John E. Mayer<\/a>, MD,<sup>d,<\/sup><sup>l<\/sup> and  <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Kheir%20JN%5BAuthor%5D\" class=\"affpopup\" co-rid=\"_co_idm140427040110272\" co-class=\"co-affbox\">John N. Kheir<\/a>, MD<sup>a,<\/sup><sup>b,<\/sup><sup>\u2217<\/sup><\/div>\n<div style=\"display:none\" class=\"contrib-group aff-tip\">\n<div id=\"_co_idm140427036931120\">\n<h3 class=\"no_margin\">Alexis R. Cole<\/h3>\n<p><sup>a<\/sup>Department of Cardiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Cole%20AR%5BAuthor%5D\">Alexis R. Cole<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427034232976\">\n<h3 class=\"no_margin\">Dorothy A. Perry<\/h3>\n<p><sup>a<\/sup>Department of Cardiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>b<\/sup>Department of Pediatrics, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Perry%20DA%5BAuthor%5D\">Dorothy A. Perry<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427039082592\">\n<h3 class=\"no_margin\">Ali Raza<\/h3>\n<p><sup>a<\/sup>Department of Cardiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>b<\/sup>Department of Pediatrics, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Raza%20A%5BAuthor%5D\">Ali Raza<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427038110528\">\n<h3 class=\"no_margin\">Arthur P. Nedder<\/h3>\n<p><sup>c<\/sup>Animal Resources at Children\u2019s Hospital, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Nedder%20AP%5BAuthor%5D\">Arthur P. Nedder<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427040062864\">\n<h3 class=\"no_margin\">Elizabeth Pollack<\/h3>\n<p><sup>c<\/sup>Animal Resources at Children\u2019s Hospital, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Pollack%20E%5BAuthor%5D\">Elizabeth Pollack<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427040060624\">\n<h3 class=\"no_margin\">William L. Regan<\/h3>\n<p><sup>d<\/sup>Department of Cardiovascular Surgery, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Regan%20WL%5BAuthor%5D\">William L. Regan<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427039634064\">\n<h3 class=\"no_margin\">Sarah J. van den Bosch<\/h3>\n<p><sup>a<\/sup>Department of Cardiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=van%20den%20Bosch%20SJ%5BAuthor%5D\">Sarah J. van den Bosch<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427011236000\">\n<h3 class=\"no_margin\">Brian D. Polizzotti<\/h3>\n<p><sup>a<\/sup>Department of Cardiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>b<\/sup>Department of Pediatrics, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Polizzotti%20BD%5BAuthor%5D\">Brian D. Polizzotti<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427039318224\">\n<h3 class=\"no_margin\">Edward Yang<\/h3>\n<p><sup>e<\/sup>Department of Radiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>f<\/sup>Department of Radiology, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Yang%20E%5BAuthor%5D\">Edward Yang<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427012209456\">\n<h3 class=\"no_margin\">Daniel Davila<\/h3>\n<p><sup>g<\/sup>Department of Neurology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>h<\/sup>Department of Neurology, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Davila%20D%5BAuthor%5D\">Daniel Davila<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427027201680\">\n<h3 class=\"no_margin\">Onur Afacan<\/h3>\n<p><sup>e<\/sup>Department of Radiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>f<\/sup>Department of Radiology, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Afacan%20O%5BAuthor%5D\">Onur Afacan<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427036188768\">\n<h3 class=\"no_margin\">Simon K. Warfield<\/h3>\n<p><sup>e<\/sup>Department of Radiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>f<\/sup>Department of Radiology, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Warfield%20SK%5BAuthor%5D\">Simon K. Warfield<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427035936096\">\n<h3 class=\"no_margin\">Yangming Ou<\/h3>\n<p><sup>b<\/sup>Department of Pediatrics, Harvard Medical School, Boston, Massachusetts<\/p>\n<p><sup>e<\/sup>Department of Radiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>f<\/sup>Department of Radiology, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Ou%20Y%5BAuthor%5D\">Yangming Ou<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427041200320\">\n<h3 class=\"no_margin\">Brenda Sefton<\/h3>\n<p><sup>d<\/sup>Department of Cardiovascular Surgery, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Sefton%20B%5BAuthor%5D\">Brenda Sefton<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427082225696\">\n<h3 class=\"no_margin\">Allen D. Everett<\/h3>\n<p><sup>i<\/sup>Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Everett%20AD%5BAuthor%5D\">Allen D. Everett<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427023452368\">\n<h3 class=\"no_margin\">Jeffrey J. Neil<\/h3>\n<p><sup>e<\/sup>Department of Radiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>f<\/sup>Department of Radiology, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Neil%20JJ%5BAuthor%5D\">Jeffrey J. Neil<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427039650608\">\n<h3 class=\"no_margin\">Hart G.W. Lidov<\/h3>\n<p><sup>h<\/sup>Department of Neurology, Harvard Medical School, Boston, Massachusetts<\/p>\n<p><sup>j<\/sup>Department of Pathology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>k<\/sup>Department of Pathology, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Lidov%20HG%5BAuthor%5D\">Hart G.W. Lidov<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427040984208\">\n<h3 class=\"no_margin\">John E. Mayer<\/h3>\n<p><sup>d<\/sup>Department of Cardiovascular Surgery, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>l<\/sup>Department of Surgery, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Mayer%20JE%5BAuthor%5D\">John E. Mayer<\/a><\/div>\n<\/div>\n<div id=\"_co_idm140427040110272\">\n<h3 class=\"no_margin\">John N. Kheir<\/h3>\n<p><sup>a<\/sup>Department of Cardiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/p>\n<p><sup>b<\/sup>Department of Pediatrics, Harvard Medical School, Boston, Massachusetts<\/p>\n<div>Find articles by <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=Kheir%20JN%5BAuthor%5D\">John N. Kheir<\/a><\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"half_rhythm\">\n<div class=\"togglers fm-copyright-license\"><a href=\"#\" class=\"pmctoggle\" rid=\"idm140427040491744_ai\">Author information<\/a> <a href=\"#\" class=\"pmctoggle\" rid=\"idm140427040491744_an\">Article notes<\/a> <a href=\"#\" class=\"pmctoggle\" rid=\"idm140427040491744_cpl\">Copyright and License information<\/a> <a href=\"\/pmc\/about\/disclaimer\/\" style=\"margin-left: 1em\">PMC Disclaimer<\/a><\/div>\n<div class=\"fm-authors-info hide half_rhythm\" id=\"idm140427040491744_ai\" style=\"display:none\">\n<div class=\"fm-affl\" id=\"aff1\"><sup>a<\/sup>Department of Cardiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff2\"><sup>b<\/sup>Department of Pediatrics, Harvard Medical School, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff3\"><sup>c<\/sup>Animal Resources at Children\u2019s Hospital, Boston Children\u2019s Hospital, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff4\"><sup>d<\/sup>Department of Cardiovascular Surgery, Boston Children\u2019s Hospital, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff5\"><sup>e<\/sup>Department of Radiology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff6\"><sup>f<\/sup>Department of Radiology, Harvard Medical School, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff7\"><sup>g<\/sup>Department of Neurology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff8\"><sup>h<\/sup>Department of Neurology, Harvard Medical School, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff9\"><sup>i<\/sup>Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland<\/div>\n<div class=\"fm-affl\" id=\"aff10\"><sup>j<\/sup>Department of Pathology, Boston Children\u2019s Hospital, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff11\"><sup>k<\/sup>Department of Pathology, Harvard Medical School, Boston, Massachusetts<\/div>\n<div class=\"fm-affl\" id=\"aff12\"><sup>l<\/sup>Department of Surgery, Harvard Medical School, Boston, Massachusetts<\/div>\n<div><span class=\"contrib-email\" id=\"contrib-a.i.b.e.s\">John N. Kheir: <a href=\"mailto:dev@null\" data-email=\"ude.dravrah.snerdlihc@riehk.nhoj\" class=\"oemail\">ude.dravrah.snerdlihc@riehk.nhoj<\/a><\/span> <\/div>\n<div id=\"cor1\"><sup>\u2217<\/sup><strong>Address for correspondence:<\/strong> Dr. John Kheir, Department of Cardiology, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115. <a href=\"mailto:dev@null\" data-email=\"ude.dravrah.snerdlihc@riehk.nhoj\" class=\"oemail\">ude.dravrah.snerdlihc@riehk.nhoj<\/a><\/div>\n<\/div>\n<div class=\"fm-article-notes hide half_rhythm\" id=\"idm140427040491744_an\" style=\"display:none\">\n<div class=\"fm-pubdate half_rhythm\">Received 2018 Sep 26; Revised 2018 Nov 6; Accepted 2018 Nov 6.<\/div>\n<\/div>\n<div class=\"permissions half_rhythm hide\" id=\"idm140427040491744_cpl\" style=\"display:none\">\n<div class=\"fm-copyright half_rhythm\"><a href=\"\/pmc\/about\/copyright\/\">Copyright<\/a> \u00a9 2019 The Authors<\/div>\n<div class=\"license half_rhythm\">This is an open access article under the CC BY-NC-ND license (http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/).<\/div>\n<\/div>\n<\/div>\n<div id=\"pmclinksbox\" class=\"links-box whole_rhythm hidden\" role=\"complementary\" aria-label=\"Related or updated information about this article.\"><\/div>\n<\/div>\n<div class=\"sec\"><\/div>\n<div id=\"ass-data\" class=\"tsec fm-sec whole_rhythm\" data-section=\"Featured_PMC_Datacitation\">\n<h2 class=\"nomenu\">Associated Data<\/h2>\n<dl data-count=\"1\" class=\"box-data-suppmats whole_rhythm no_bottom_margin\">\n<dt><a href=\"#\" rid=\"data-suppmats\" data-ga-action=\"click_feat_toggler\" data-ga-label=\"Supplementary Materials\" class=\"pmctoggle\">Supplementary Materials<\/a><\/dt>\n<dd id=\"data-suppmats\" style=\"display: none;\">\n<div class=\"half_rhythm\">\n<div class=\"caption half_rhythm no_bottom_margin\">Supplemental Figures&nbsp;S1\u2013S8 and Supplemental Table&nbsp;1<\/div>\n<div><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/bin\/mmc1.pdf\" data-ga-action=\"click_feat_suppl\">mmc1.pdf<\/a><span style=\"color:gray\"> (1.2M)<\/span><\/div>\n<div class=\"small guid\">GUID:&nbsp;AD5D5007-E593-48DF-AD21-A1D7D8AA53C8<\/div>\n<\/div>\n<\/dd>\n<\/dl>\n<\/div>\n<div id=\"abs0015\" lang=\"en\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><span role=\"menubar\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"menuitem\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/span><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"abs0015title\">Visual Abstract<\/h2>\n<p><!--article-meta--><\/p>\n<div><!--fig ft0--><!--fig @position=\"anchor\" mode=article f4--><!--fig mode=\"anchored\" f5--><\/p>\n<div class=\"fig graphic_only iconblock anchored whole_rhythm\" id=\"undfig1\"><!--fig\/graphic|fig\/alternatives\/graphic mode=\"anchored\" m1--><\/p>\n<div class=\"figure\" data-largeobj=\"\" data-largeobj-link-rid=\"largeobj_idm140427044851152\"><a class=\"inline_block ts_canvas\" href=\"\/core\/lw\/2.0\/html\/tileshop_pmc\/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&amp;p=PMC3&amp;id=6488769_fx1.jpg\" target=\"tileshopwindow\" rel=\"noopener\"><\/p>\n<div class=\"ts_bar small\" title=\"Click on image to zoom\"><\/div>\n<p><img decoding=\"async\" loading=\"lazy\" alt=\"An external file that holds a picture, illustration, etc.\nObject name is fx1.jpg\" title=\"Click on image to zoom\" class=\"tileshop\" src=\"https:\/\/hho-bulgaria.com\/wp-content\/uploads\/2024\/01\/fx1.jpg\"><\/a><\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm140427044851152\" style=\"display: none;\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/undfig1\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<\/div>\n<\/div>\n<div class=\"sec\"><strong class=\"kwd-title\">Key Words: <\/strong><span class=\"kwd-text\">circulatory arrest, hydrogen gas, ischemia-reperfusion injury, neuroprotection<\/span><\/div>\n<div class=\"sec\"><strong class=\"kwd-title\">Abbreviations and Acronyms: <\/strong><span class=\"kwd-text\">CPB, cardiopulmonary bypass; GFAP, glial fibrillatory acidic protein; H<sub>2<\/sub>, hydrogen gas; \u2022OH, hydroxyl radical; PDI, Psychomotor Development Index; SNDS, Swine Neurodevelopment Score<\/span><\/div>\n<\/div>\n<div id=\"abs0020\" lang=\"en\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"abs0020title\">Highlights<\/h2>\n<p><!--article-meta--><\/p>\n<div>\n<ul class=\"simple\" style=\"list-style-type:none\" id=\"ulist0010\">\n<li class=\"a_label\" id=\"u0010\">\n<div class=\"inline_block a_label\">\u2022<\/div>\n<div id=\"p0010\">Inhaled hydrogen gas has been shown to temper the sequelae of ischemic insults. Its application in cardiopulmonary bypass has not been investigated.<\/div>\n<\/li>\n<li class=\"a_label\" id=\"u0015\">\n<div class=\"inline_block a_label\">\u2022<\/div>\n<div id=\"p0015\">Neonatal swine were cannulated to cardiopulmonary bypass and exposed to prolonged circulatory arrest (75&nbsp;min at 25\u00b0C). Swine were randomized to treatment with or without inhaled 2.4% hydrogen gas mixtures for 24 h during and following ischemic injury. Hydrogen-treated swine exhibited significantly less severe brain injury than controls, as quantified by clinical examination, serology, magnetic resonance-graded volume of injury, and histopathology. Hydrogen treatment also decreased renal&nbsp;injury.<\/div>\n<\/li>\n<li class=\"a_label\" id=\"u0020\">\n<div class=\"inline_block a_label\">\u2022<\/div>\n<div id=\"p0020\">The administration of inhaled 2.4% hydrogen gas mixtures through a standard ventilator and anesthesia machine were safe, even in the setting of electrocautery.<\/div>\n<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<div id=\"abs0010\" lang=\"en\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"abs0010title\">Summary<\/h2>\n<p><!--article-meta--><\/p>\n<div>\n<p class=\"p p-first-last\">This study used a swine model of mildly hypothermic prolonged circulatory arrest and found that the addition of 2.4% inhaled hydrogen gas to inspiratory gases during and after the ischemic insult significantly decreased neurologic and renal injury compared with controls. With proper precautions, inhalational hydrogen may be administered safely through conventional ventilators and may represent a complementary therapy that can be easily incorporated into current workflows. In the future, inhaled hydrogen may diminish the sequelae of ischemia that occurs in congenital heart surgery, cardiac arrest, extracorporeal life-support events, acute myocardial infarction, stroke, and organ transplantation.<\/p>\n<\/div>\n<\/div>\n<div id=\"body-a.j\" class=\"tsec sec\">\n<h2 class=\"headless nomenu\"><\/h2>\n<p id=\"p0025\" class=\"p p-first\">Newborns with critical congenital heart disease often undergo major surgical interventions in the neonatal period that require the use of cardiopulmonary bypass (CPB). Several studies have provided radiographic evidence showing that new ischemic injury occurs following CPB <a href=\"#bib1\" rid=\"bib1\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">1<\/a>, <a href=\"#bib2\" rid=\"bib2\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">2<\/a>, <a href=\"#bib3\" rid=\"bib3\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">3<\/a>, <a href=\"#bib4\" rid=\"bib4\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">4<\/a>, <a href=\"#bib5\" rid=\"bib5\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">5<\/a>, <a href=\"#bib6\" rid=\"bib6\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">6<\/a>, <a href=\"#bib7\" rid=\"bib7\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">7<\/a>. Neonates with the diagnosis of left heart obstructive lesions are consistently at the highest risk of cerebral injury <a href=\"#bib5\" rid=\"bib5\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">5<\/a>, <a href=\"#bib8\" rid=\"bib8\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">8<\/a>. In 1 study <a href=\"#bib1\" rid=\"bib1\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(1)<\/a>, new white matter injury (i.e., not present preoperatively) was evident in more than 70% of&nbsp;neonates undergoing aortic arch reconstruction. Cerebral injuries included moderate or severe white matter injury in 40% to 50% of patients; new infarctions were found in one-third of patients. Further, clinically evident seizures have been reported in up to 20% of neonates following surgery for congenital heart disease and are more common in patients undergoing prolonged deep hypothermic circulatory arrest <a href=\"#bib9\" rid=\"bib9\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">9<\/a>, <a href=\"#bib10\" rid=\"bib10\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">10<\/a>. Subclinical seizures occur in an even higher fraction <a href=\"#bib1\" rid=\"bib1\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">1<\/a>, <a href=\"#bib10\" rid=\"bib10\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">10<\/a>, <a href=\"#bib11\" rid=\"bib11\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">11<\/a>. The presence of postoperative seizures is an important marker of underlying ischemic injury, which may manifest as radiologic injury and developmental delay years later <a href=\"#bib12\" rid=\"bib12\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(12)<\/a>. Thus, although abnormal neurodevelopment in infants with critical congenital heart disease is multifactorial (including in utero, genetic, and socioeconomic risk factors) <a href=\"#bib13\" rid=\"bib13\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(13)<\/a>, injury occurring during CPB represents a significant contributor to neurologic impairment.<\/p>\n<p id=\"p0030\">To mitigate this problem, nearly all operations are performed under some degree of hypothermia, which suppresses cerebral oxygen consumption <a href=\"#bib14\" rid=\"bib14\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(14)<\/a>, and enhances preservation of high-energy phosphates, and reduces the accumulation of toxic metabolites <a href=\"#bib15\" rid=\"bib15\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(15)<\/a>. Cerebral hypoxia can be monitored using cerebral near-infrared spectroscopy and the degree and duration of cerebral hypoxia have been associated with subsequent neurologic impairment. For example, newborns experiencing a regional cerebral oxyhemoglobin saturation index&nbsp;&lt;40 exhibited worse receptive communication at 2 years of age than those who did not <a href=\"#bib16\" rid=\"bib16\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(16)<\/a>. Efforts to minimize cerebral hypoxia&nbsp;during congenital heart surgery have resulted in improvements in neurologic outcomes. For example, the addition of carbon dioxide during hypothermia (i.e., pH-stat, which promotes cerebral vasodilation during bypass) was associated with a more rapid return of normal electroencephalographic activity <a href=\"#bib17\" rid=\"bib17\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(17)<\/a>. In another study <a href=\"#bib18\" rid=\"bib18\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(18)<\/a>, target hematocrit during CPB was significantly associated with Psychomotor Development Index (PDI) scores at 1 year of age <a href=\"#bib18\" rid=\"bib18\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(18)<\/a>.<\/p>\n<p id=\"p0035\" class=\"p\">At a cellular level, cerebral hypoxia during CPB creates a complex cascade of changes within the inner mitochondrial membrane, causing formation of the&nbsp;superoxide anion radical (O<sub>2<\/sub><sup>\u2212\u2022<\/sup>) <a href=\"#bib19\" rid=\"bib19\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(19)<\/a>, which in turn generates hydroxyl radicals (\u2022OH) by the Fenton reaction. The \u2022OH is the strongest of the oxidant species and reacts indiscriminately with nucleic acids, lipids, and proteins, causing direct cellular injury and stimulating&nbsp;apoptosis. Because there is no known detoxification system for \u2022OH, scavenging \u2022OH is a critical antioxidant process <a href=\"#bib20\" rid=\"bib20\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(20)<\/a>. Recently, it has been&nbsp;discovered that hydrogen gas (i.e., molecular dihydrogen [H<sub>2<\/sub>]) selectively reduces \u2022OH in&nbsp;vivo (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig1\/\" target=\"figure\" class=\"fig-table-link figpopup\" rid-figpopup=\"fig1\" rid-ob=\"ob-fig1\" co-legend-rid=\"lgnd_fig1\" rel=\"noopener\"><span>Figure&nbsp;1<\/span><\/a>) <a href=\"#bib21\" rid=\"bib21\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(21)<\/a>. For example, rodents breathing either 2% or 4% H<sub>2<\/sub> for 90 min following a period of middle cerebral artery occlusion exhibited a substantially smaller infarct volume, improved neurologic scores, weight gain, and thermoregulation relative to controls <a href=\"#bib21\" rid=\"bib21\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(21)<\/a>, findings that were repeated by an independent group <a href=\"#bib22\" rid=\"bib22\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(22)<\/a>. In another study <a href=\"#bib23\" rid=\"bib23\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(23)<\/a>, H<sub>2<\/sub>-treated rodents undergoing a 5-min period of asphyxial cardiac arrest exhibited more favorable neurologic scores, improved myocardial function, and improved 96-h survival than&nbsp;did those treated with targeted temperature management alone. Here, we studied the effects of inhalational H<sub>2<\/sub>&nbsp;gas on neurologic outcomes in neonatal swine undergoing cerebral hypoxic-ischemic injury in the setting of hypothermic CPB. We hypothesized that the inhalation of H<sub>2<\/sub> gas surrounding a CPB-related ischemic injury would diminish the degree of neurologic injury&nbsp;in subject animals relative to that in control animals.<\/p>\n<p><!--fig ft0--><!--fig mode=article f1--><\/p>\n<div class=\"fig iconblock whole_rhythm\" id=\"fig1\" co-legend-rid=\"lgnd_fig1\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig1\/\" target=\"figure\" rid-figpopup=\"fig1\" rid-ob=\"ob-fig1\" rel=\"noopener\"><!--fig\/graphic|fig\/alternatives\/graphic mode=\"anchored\" m1--><\/a><\/p>\n<div class=\"figure\" data-largeobj=\"\" data-largeobj-link-rid=\"largeobj_idm140427040040768\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig1\/\" target=\"figure\" rid-figpopup=\"fig1\" rid-ob=\"ob-fig1\" rel=\"noopener\"><\/a><a class=\"inline_block ts_canvas\" href=\"\/core\/lw\/2.0\/html\/tileshop_pmc\/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&amp;p=PMC3&amp;id=6488769_gr1.jpg\" target=\"tileshopwindow\" rel=\"noopener\"><\/p>\n<div class=\"ts_bar small\" title=\"Click on image to zoom\"><\/div>\n<p><img decoding=\"async\" loading=\"lazy\" alt=\"An external file that holds a picture, illustration, etc.\nObject name is gr1.jpg\" title=\"Click on image to zoom\" class=\"tileshop\" src=\"https:\/\/hho-bulgaria.com\/wp-content\/uploads\/2024\/01\/gr1.jpg\"><\/a><\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm140427040040768\" style=\"display: none;\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig1\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"icnblk_cntnt\" id=\"lgnd_fig1\">\n<div><a class=\"figpopup\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig1\/\" target=\"figure\" rid-figpopup=\"fig1\" rid-ob=\"ob-fig1\" rel=\"noopener\">Figure&nbsp;1<\/a><\/div>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Presumed Mechanism of H<sub>2<\/sub> Action in the Setting of Ischemia<\/p>\n<p>Ischemic insults create tissue hypoxia, stimulating a complex cascade (not shown) that results in the release of superoxide (O<sub>2<\/sub><sup>\u2212\u2022<\/sup>). When O<sub>2<\/sub><sup>\u2212\u2022<\/sup> is present in excess (i.e., when compensatory mechanisms become saturated), it directly causes the reduction of transition metal ions, including Fe<sup>3+<\/sup> and Cu<sup>2+<\/sup>, which in turn, generates hydroxyl radicals (\u2022OH) by the Fenton reaction. The \u2022OH is the strongest of the oxidant species and is the direct effector of DNA injury and lipid membrane peroxidation, which releases HNE and MDA, causing direct cellular injury and stimulating apoptosis. Unlike O<sub>2<\/sub><sup>\u2212\u2022<\/sup> and H<sub>2<\/sub>O<sub>2<\/sub>, there is no known detoxification system for \u2022OH; therefore, scavenging \u2022OH is a critical antioxidant process. Molecular hydrogen (H<sub>2<\/sub>), which freely permeates the cell wall and diffuses into the cytosol and mitochondria, reduces the hydroxyl radical to water and thus mitigates \u2022OH-mediated tissue injury. HNE&nbsp;= 4-hydroxyl-2-nonenal; MDA&nbsp;= malondialdehyde; SOD&nbsp;=&nbsp;superoxide dismutase.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"sec1\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec1title\">Methods<\/h2>\n<p id=\"p0040\" class=\"p p-first\">The following protocol was approved by the Institutional Animal Care and Use Committee at Boston Children\u2019s Hospital (protocol 15-08-2990) (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig2\/\" target=\"figure\" class=\"fig-table-link figpopup\" rid-figpopup=\"fig2\" rid-ob=\"ob-fig2\" co-legend-rid=\"lgnd_fig2\" rel=\"noopener\"><span>Figure&nbsp;2<\/span><\/a>), which included a review of hydrogen-related environmental hazard concerns.<\/p>\n<p><!--fig ft0--><!--fig mode=article f1--><\/p>\n<div class=\"fig iconblock whole_rhythm\" id=\"fig2\" co-legend-rid=\"lgnd_fig2\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig2\/\" target=\"figure\" rid-figpopup=\"fig2\" rid-ob=\"ob-fig2\" rel=\"noopener\"><!--fig\/graphic|fig\/alternatives\/graphic mode=\"anchored\" m1--><\/a><\/p>\n<div class=\"figure\" data-largeobj=\"\" data-largeobj-link-rid=\"largeobj_idm140427044342080\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig2\/\" target=\"figure\" rid-figpopup=\"fig2\" rid-ob=\"ob-fig2\" rel=\"noopener\"><\/a><a class=\"inline_block ts_canvas\" href=\"\/core\/lw\/2.0\/html\/tileshop_pmc\/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&amp;p=PMC3&amp;id=6488769_gr2.jpg\" target=\"tileshopwindow\" rel=\"noopener\"><\/p>\n<div class=\"ts_bar small\" title=\"Click on image to zoom\"><\/div>\n<p><img decoding=\"async\" loading=\"lazy\" alt=\"An external file that holds a picture, illustration, etc.\nObject name is gr2.jpg\" title=\"Click on image to zoom\" class=\"tileshop\" src=\"https:\/\/hho-bulgaria.com\/wp-content\/uploads\/2024\/01\/gr2.jpg\"><\/a><\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm140427044342080\" style=\"display: none;\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig2\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"icnblk_cntnt\" id=\"lgnd_fig2\">\n<div><a class=\"figpopup\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig2\/\" target=\"figure\" rid-figpopup=\"fig2\" rid-ob=\"ob-fig2\" rel=\"noopener\">Figure&nbsp;2<\/a><\/div>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Study Protocol<\/p>\n<p>Neonatal swine were acclimated with bottle feedings 5 time per day <strong>(blue marks)<\/strong> for 5 days prior to experimentation. On the day of experimentation, swine were anesthetized and instrumented for cardiopulmonary bypass. Ischemic injury included circulatory arrest for 75 min at 25\u00b0C. Swine were then rewarmed and decannulated and underwent mechanical ventilation using a standardized intensive care protocol. Swine were ventilated for a total of 24 h (including pre- and post-operative treatments) with or without 2.4% inhaled hydrogen therapy (n&nbsp;= 8 swine per group). Videotaped neurologic examinations <strong>(green marks)<\/strong> took place prior to and daily following the circulatory arrest period. Swine underwent sedated brain MRI followed by terminal cerebral perfusion for histopathologic examination on postoperative day 3. F&nbsp;= Friday; M&nbsp;= Monday; MRI = magnetic resonance imaging; R&nbsp;= Thursday; RN&nbsp;= nursing care; S&nbsp;= Saturday\/Sunday; W&nbsp;= Wednesday.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"sec1.1\" class=\"sec\">\n<h3 id=\"sec1.1title\">Experimental protocol<\/h3>\n<p id=\"p0045\" class=\"p p-first-last\">Sixteen neonatal female Yorkshire swine (3.8 to 5.8 kg; post-natal age: 6&nbsp;to 10&nbsp;days of life) were acclimated to their surroundings and bottle fed 5 times daily by research staff for 6&nbsp;days. On the day of experimentation, swine were&nbsp;anesthetized by intramuscular injections of tiletamine (Telazol), xylazine and atropine, and tracheally intubated. Swine were then sedated by using inhaled isoflurane (0.25% to 2%). Neuromuscular blockade (cisatracurium) was administered upon anesthetic induction and then again prior to sternotomy incision. A right femoral arterial (3-F sheath) catheter and a right internal jugular venous (4-F, 5 cm) catheter were placed and continuously transduced. Esophageal and rectal temperature probes were placed. A median sternotomy was performed, a subtotal thymectomy performed, and the pericardium opened. A sterile human infant-sized CPB circuit (S5&nbsp;infant perfusion pack, Sorin Group, Arvada, Colorado) was primed with blood from an adult donor swine sacrificed on&nbsp;the previous day. The right atrium and ascending aorta were cannulated (18-F DLP malleable single-stage venous and 10-F arterial cannulas, Medtronic-Biomedicus, Eden Prairie, Minnesota), and full-flow CPB was instituted. As is our institution&#8217;s clinical practice, a dose of methylprednisolone (30&nbsp;mg\/kg intravenous [IV]) was administered upon initiation of CPB. Swine were then cooled to 25\u00b0C (measured rectally) over 30 min, using&nbsp;a pH-stat management strategy (carbon dioxide added). Following cooling, the aorta was cross-clamped, and a solution of cold blood, potassium, magnesium, and lidocaine were administered into the aortic root, and&nbsp;cardioplegia was induced (del Nido Cardioplegia Solution <a href=\"#bib24\" rid=\"bib24\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">[24]<\/a>), causing prompt diastolic arrest. Circulation was then discontinued for a 75-min period of circulatory arrest. Rectal temperature was maintained as close to 25\u00b0C as possible by using surface cooling as needed. Following circulatory arrest, circulation was restored, and swine were warmed to 37\u00b0C over 60&nbsp;min. Swine were then weaned from CPB using inotropic support as needed to maintain systolic blood pressure &gt;80 mm&nbsp;Hg. Cannulas were removed, hemostasis ensured, and the sternum closed.<\/p>\n<\/div>\n<div id=\"sec1.2\" class=\"sec\">\n<h3 id=\"sec1.2title\">Survival period<\/h3>\n<p id=\"p0050\" class=\"p p-first\">Sedation was then transitioned to infusions of propofol (1 to 3 mg\/kg\/h) and&nbsp;fentanyl (1 to 2 \u03bcg\/kg\/h), and inhalational isoflurane was discontinued for an 18-h period of regimented intensive care staffed by intensive care nursing staff. During this time, esophageal temperature was continuously monitored and maintained below 38\u00b0C by using a cooling blanket. Blood pressure was maintained with an infusion of dopamine (3 to 5&nbsp;\u03bcg\/kg\/min, titrated to systolic blood pressure &gt;70 mm&nbsp;Hg). Diuresis was achieved by using furosemide (1 mg\/kg every 12 h). Mechanical ventilation was continued by using synchronized, intermittent mandatory ventilation with a fraction of inspired oxygen, required to maintain pulse oximetry saturation of 95% and target tidal volumes of 8 ml\/kg. Animals were continuously monitored for clinical seizure activity. Seizures lasting longer than 2 min were treated according to a protocol of lorazepam (0.1&nbsp;mg\/kg IV every 5 min up to 3 doses), then phenobarbital (20 mg\/kg IV every 20 min for 2 doses), then fosphenytoin (20 mg\/kg IV every 20 min for&nbsp;2&nbsp;doses), then an increase in the rate of propofol&nbsp;infusion (up to 10 mg\/kg\/h). Inotrope score was calculated as: [dopamine (\u03bcg\/kg\/min)&nbsp;+ dobutamine (\u03bcg\/kg\/min)&nbsp;+ 100\u00d7 epinephrine (\u03bcg\/kg\/min)] <a href=\"#bib25\" rid=\"bib25\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(25)<\/a>.<\/p>\n<p id=\"p0055\" class=\"p p-last\">After the animals underwent 18 h of intensive care, the arterial catheter, thoracic drain, and tracheal tube were removed. Swine were then observed for 3 days, with quantification of neurologic status by daily neurologic examinations. Blood drawn prior to and daily after the injury was analyzed for complete blood count, chemistry profile, hepatic transaminases, and venous blood gas analysis. Glial fibrillatory acidic protein (GFAP) was assessed using an electrochemiluminescent sandwich immunoassay (Meso Scale Diagnostics, Rockville, Maryland), with a detection range of 0.001 to 40.0 ng\/ml <a href=\"#bib26\" rid=\"bib26\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(26)<\/a>.<\/p>\n<\/div>\n<div id=\"sec1.3\" class=\"sec\">\n<h3 id=\"sec1.3title\">Inhaled hydrogen therapy<\/h3>\n<p id=\"p0060\" class=\"p p-first-last\">Animals were randomized to treatments as described above with or without inhaled hydrogen (2.40%) for a 24-h period during and after the ischemic injury (n&nbsp;= 8 per group). At the beginning of the study, we created a table that dictated the treatment allocation for each experiment in random order, according to which patients were treated. Due to environmental hazards and logistical considerations, members of the veterinary, perfusion, and overnight nursing staff were not blinded to treatment group allocation, whereas surgical staff, neurologists, and histopathologists were blinded to treatment allocation. Premixed, certified hydrogen gas blends containing 2.40 \u00b1 0.05% of grade-6 purity (99.9999%) hydrogen gas with either balance medical air or medical oxygen (Praxair Distribution, Inc., Jessup, Maryland) were obtained and received as nonflammable gas mixtures. These tanks were fitted with a 50-psi regulator and a flash arrestor and then attached directly to the air and oxygen (respectively) inlets of the anesthesia machine (Dr\u00e4ger Apollo, Coppell, Texas) during the experimental period and to the mechanical ventilator (Servo I model, Maquet, Gothenburg, Sweden) during the survival period (<a href=\"#appsec1\" rid=\"appsec1\" class=\" sec\">Supplemental Figure&nbsp;S1<\/a>). Additional hydrogenated \u201ccarbogen\u201d mixtures were made,&nbsp;including 0%, 4%, 6%, and 8% carbon dioxide, 2.40% hydrogen, and balance oxygen for use during&nbsp;hypothermic perfusion. Ambient hydrogen concentrations were measured continuously (Eagle 2 model, RKI Instruments, Union City, California).<\/p>\n<\/div>\n<div id=\"sec1.4\" class=\"sec\">\n<h3 id=\"sec1.4title\">Swine neurologic deficit scores<\/h3>\n<p id=\"p0065\" class=\"p p-first-last\">Swine were evaluated prior to and following each 24-h period after the injury using a previously described swine neurologic deficit score (SNDS) <a href=\"#bib27\" rid=\"bib27\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(27)<\/a> by 2 research technicians, present for each examination (unblinded to treatment allocation), and 2 neurologists (by review of videotaped examinations, blinded to treatment allocation). The mean of the 4 scores was taken at each time point. The examination assessed cranial nerve function, respiratory pattern, motor and sensory function, level of consciousness, and behavior, each assigned a total of 100 points. Points were assigned based on specific abnormal neurologic findings (<a href=\"#appsec1\" rid=\"appsec1\" class=\" sec\">Supplemental Table&nbsp;1<\/a>), such that a score of 0 was normal, and a score of 500 represented brain death. The presence or absence of clinical seizures was not part of the scoring system.<\/p>\n<\/div>\n<div id=\"sec1.5\" class=\"sec\">\n<h3 id=\"sec1.5title\">Brain magnetic resonance imaging<\/h3>\n<p id=\"p0070\" class=\"p p-first-last\">On day 3 post-injury, swine were anesthetized for brain magnetic resonance imaging (MRI) (3-T Skyra model scanner, 64-channel head and neck coil, Siemens, Corp., Munich, Germany). High-resolution T1, T2, fluid-attenuated inversion recovery, and diffusion-weighted images were obtained. Areas of enhancement on axial and coronal T2 and apparent diffusion coefficient images were manually assessed on a&nbsp;voxel-per-voxel basis and outlined (itk-SNAP software application, Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, and Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah) by a radiology technician (Mr. Abdelhakim Ouaalam, Department of Radiology, Boston Children&#8217;s Hospital, Boston, Massachusetts), a radiologist (E.Y.), and a clinical neurologist (J.N.), all of whom were blinded to treatment allocation. From these values, total volumes of cranial injuries per swine were calculated using in-house software normalized to brain volume, and the total volumes of injuries were compared between groups by using the Mann-Whitney <em>U<\/em> test.<\/p>\n<\/div>\n<div id=\"sec1.6\" class=\"sec\">\n<h3 id=\"sec1.6title\">Neurohistopathology<\/h3>\n<p id=\"p0075\" class=\"p p-first-last\">Following brain MRI of the swine on post-injury day 3, both carotid arteries and jugular veins were then cannulated by cutdown and perfused with normal saline (2 l), followed by 4% paraformaldehyde (4 l). The heads of swine were fixed in 10% formaldehyde for 24&nbsp;h and then removed and paraffin embedded and&nbsp;then stained for hematoxylin and eosin. Hypoxic-ischemic injuries of the frontal cortex, temporal cortex, hippocampus, dentate gyrus, caudate nucleus, and thalamus were graded according to a previously defined scale by a pathologist (H.G.W.L.) blinded to treatment allocation. Briefly, histologic injury was evaluated by using both light and fluorescence microscopy <a href=\"#bib28\" rid=\"bib28\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(28)<\/a> on a scale of 0 through 5 for each of 6 regions, as follows: 0&nbsp;= normal, no injury; 1&nbsp;= rare hypereosinophilic neurons; 2&nbsp;= small clusters of hypereosinophilic neurons; 3&nbsp;= majority of neurons (&gt;50%) are hypereosinophilic; 4&nbsp;= significant damage to neurons; and 5&nbsp;= cavitated infarction with histologic necrosis. Animals that did not survive for 3 days (due to refractory status epilepticus) were assigned the median histologic score for animals in the control group.<\/p>\n<\/div>\n<div id=\"sec1.7\" class=\"sec sec-last\">\n<h3 id=\"sec1.7title\">Statistical analysis<\/h3>\n<p id=\"p0080\" class=\"p p-first\">The primary outcome of this study was neurologically intact survival, which was defined as an SNDS of&nbsp;\u2264120 at 3 days, compared between groups using a log-rank test (Gehan-Breslow-Wilcoxon test). On the basis of a previous series of pilot experiments, 15% of animals in the control group were expected to meet this endpoint, and the study was powered to identify the fact that 70% or more in the hydrogen treatment group met this endpoint at 5 days with 80% power and an alpha level of 0.05.<\/p>\n<p id=\"p0085\" class=\"p p-last\">Between-group differences in SNDS, regional neurohistologic scores, body temperatures, regional oxyhemoglobin saturation index values, hemodynamics, inotrope scores, serum lactic acid concentrations, blood gas concentrations, PaO<sub>2<\/sub>\/FiO<sub>2<\/sub> ratios, chemistry values, and hematologic parameters were assessed over time by using 2-way repeated measures analysis of variance (ANOVA), using Prism version 7.00 software (for MacIntosh [Cupertino, California], GraphPad, La Jolla, California). In order to complete ANOVA, missing values for the 2 animals which were sacrificed early were estimated to be the median values across controls for that time point. When results were statistically significant, time-dependent differences between groups were assessed by using Sidak\u2019s multiple comparisons test. Interobserver reliability for SNDS was assessed by Pearson coefficient between blinded versus unblinded observers for time-matched pairs. Single time point values, such as differences in cerebral infarct volumes or changes in GFAP relative to baseline, were compared between groups by Student\u2019s <em>t<\/em>-test or Mann-Whitney <em>U<\/em> test, as appropriate. For all tests, a p value of&nbsp;&lt;0.05 was considered statistically significant.<\/p>\n<\/div>\n<\/div>\n<div id=\"sec2\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec2title\">Results<\/h2>\n<div id=\"sec2.1\" class=\"sec sec-first\">\n<h3 id=\"sec2.1title\">Hydrogen hazards<\/h3>\n<p id=\"p0090\" class=\"p p-first-last\">Hydrogen-oxygen and hydrogen-air mixtures were administered via the anesthesia machine and mechanical ventilator without malfunction or incident. Electrocautery was used with no subjective difference in performance between controls and the hydrogen-treated animals. Measurements of ambient hydrogen concentrations were below the lower limit of detection (&lt;1 ppm) at all time points.<\/p>\n<\/div>\n<div id=\"sec2.2\" class=\"sec\">\n<h3 id=\"sec2.2title\">Clinical outcomes<\/h3>\n<p id=\"p0095\" class=\"p p-first\">All animals were successfully weaned from CPB. The degrees to which hypothermia was achieved were similar between the groups (mean rectal temperature: 27.4 \u00b1 1.8\u00b0C vs. 26.5 \u00b1 1.9\u00b0C in controls and hydrogen-treated groups, respectively; p&nbsp;= 0.2387) (<a href=\"#appsec1\" rid=\"appsec1\" class=\" sec\">Supplemental Figure&nbsp;S2<\/a>). Cerebral and somatic near infrared spectroscopy values were also similar between groups, frequently reaching a nadir of&nbsp;&lt;20 during the deep hypothermic circulatory arrest period (<a href=\"#appsec1\" rid=\"appsec1\" class=\" sec\">Supplemental Figure&nbsp;S3<\/a>). Two swine in the control group exhibited refractory status epilepticus and were sacrificed at 32 and 36 h post-injury following a failed trial of extubation; no hydrogen-treated animals exhibited seizures. Survival to 3&nbsp;days was similar between groups (log rank test: p&nbsp;=&nbsp;0.1435). Hydrogen-treated swine exhibited a higher rate of neurologically intact survival, defined as an SNDS of&nbsp;\u2264120 at the time of death (log-rank test; p&nbsp;= 0.0035) (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig3\/\" target=\"figure\" class=\"fig-table-link figpopup\" rid-figpopup=\"fig3\" rid-ob=\"ob-fig3\" co-legend-rid=\"lgnd_fig3\" rel=\"noopener\"><span>Figure&nbsp;3A<\/span><\/a>). SNDSs were significantly improved in hydrogen-treated swine in the postoperative period (p&nbsp;&lt; 0.0001) (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig3\/\" target=\"figure\" class=\"fig-table-link figpopup\" rid-figpopup=\"fig3\" rid-ob=\"ob-fig3\" co-legend-rid=\"lgnd_fig3\" rel=\"noopener\"><span>Figure&nbsp;3B<\/span><\/a>). Interobserver reliability was excellent among in-person scorers (i.e., unblinded research team members) and videotaped reviewers (i.e., blinded neurologists) (Pearson correlation coefficient: 0.895). The increase in serum GFAP concentrations relative to those at baseline was significantly higher in controls than in H<sub>2<\/sub>-treated swine at 60 min post-injury (p&nbsp;= 0.0068) (<a href=\"#appsec1\" rid=\"appsec1\" class=\" sec\">Supplemental Figure&nbsp;S4<\/a>).<\/p>\n<p><!--fig ft0--><!--fig mode=article f1--><\/p>\n<div class=\"fig iconblock whole_rhythm\" id=\"fig3\" co-legend-rid=\"lgnd_fig3\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig3\/\" target=\"figure\" rid-figpopup=\"fig3\" rid-ob=\"ob-fig3\" rel=\"noopener\"><!--fig\/graphic|fig\/alternatives\/graphic mode=\"anchored\" m1--><\/a><\/p>\n<div class=\"figure\" data-largeobj=\"\" data-largeobj-link-rid=\"largeobj_idm140427041384624\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig3\/\" target=\"figure\" rid-figpopup=\"fig3\" rid-ob=\"ob-fig3\" rel=\"noopener\"><\/a><a class=\"inline_block ts_canvas\" href=\"\/core\/lw\/2.0\/html\/tileshop_pmc\/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&amp;p=PMC3&amp;id=6488769_gr3.jpg\" target=\"tileshopwindow\" rel=\"noopener\"><\/p>\n<div class=\"ts_bar small\" title=\"Click on image to zoom\"><\/div>\n<p><img decoding=\"async\" loading=\"lazy\" alt=\"An external file that holds a picture, illustration, etc.\nObject name is gr3.jpg\" title=\"Click on image to zoom\" class=\"tileshop\" src=\"https:\/\/hho-bulgaria.com\/wp-content\/uploads\/2024\/01\/gr3.jpg\"><\/a><\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm140427041384624\" style=\"display: none;\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig3\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"icnblk_cntnt\" id=\"lgnd_fig3\">\n<div><a class=\"figpopup\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig3\/\" target=\"figure\" rid-figpopup=\"fig3\" rid-ob=\"ob-fig3\" rel=\"noopener\">Figure&nbsp;3<\/a><\/div>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Clinical Neurologic Outcomes<\/p>\n<p><strong>(A)<\/strong> Hydrogen-treated swine exhibited significantly higher rates of neurologically intact survival, which was defined as an SNDS&nbsp;\u2264120 at the time of death (log-rank test: p&nbsp;= 0.0035). The overall rates of survival were similar between groups (log-rank test: p&nbsp;= 0.1435). <strong>(B)<\/strong> Hydrogen-treated swine exhibited significantly lower SNDS at 1, 2, and 3 days post injury (2-way ANOVA: p&nbsp;&lt; 0.0001). Data for day 1 represent 8&nbsp;swine per group; data for days 2 and 3 represent 8 swine in the hydrogen group and 6 in the control group (2 swine allocated to the control group died from refractory seizures and could not be successfully extubated). ***p&nbsp;&lt; 0.001; **p&nbsp;&lt;&nbsp;0.01 for daily differences according to Sidak\u2019s multiple comparisons post test. ANOVA&nbsp;= analysis of variance; DHCA&nbsp;= deep hypothermic circulatory arrest; SNDS&nbsp;= Swine Neurodevelopment Score.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<p id=\"p0100\" class=\"p p-last\">Relative to controls, H<sub>2<\/sub>-treated swine exhibited a significantly lower level of serum creatinine during the survival period (p&nbsp;= 0.0152), an average of 0.38 mg\/dl lower by postoperative day 3. There were no differences in serum markers of hepatic injury or function (<a href=\"#appsec1\" rid=\"appsec1\" class=\" sec\">Supplemental Figure&nbsp;S5<\/a>). There were no significant differences in acute hemodynamics, and inotrope scores were similar between the groups (<a href=\"#appsec1\" rid=\"appsec1\" class=\" sec\">Supplemental Figure&nbsp;S6<\/a>). In the postoperative period, there were no differences in PaO<sub>2<\/sub>\/FiO<sub>2<\/sub> ratios as a marker of lung function (p&nbsp;= 0.92), nor were there significant differences in blood gas values during the postoperative period (<a href=\"#appsec1\" rid=\"appsec1\" class=\" sec\">Supplemental Figure&nbsp;S7<\/a>). Similarly, there were no significant differences in hematologic endpoints between groups during the survival period (<a href=\"#appsec1\" rid=\"appsec1\" class=\" sec\">Supplemental Figure&nbsp;S8<\/a>).<\/p>\n<\/div>\n<div id=\"sec2.3\" class=\"sec\">\n<h3 id=\"sec2.3title\">Neuroradiology<\/h3>\n<p id=\"p0105\" class=\"p p-first-last\">Swine in both groups exhibited a radiographic predominance of frontal and temporal lobe injuries. However, H<sub>2<\/sub>-treated swine exhibited significantly lower volumes of white matter injury on T2 imaging than did controls (median: 134 mm<sup>3<\/sup> [interquartile range [IQR]: 84 to 200 mm<sup>3<\/sup>] in H<sub>2<\/sub>-treated swine vs. 383 mm<sup>3<\/sup> [IQR: 77 to 639 mm<sup>3<\/sup>] in controls; p&nbsp;= 0.0460) (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig4\/\" target=\"figure\" class=\"fig-table-link figpopup\" rid-figpopup=\"fig4\" rid-ob=\"ob-fig4\" co-legend-rid=\"lgnd_fig4\" rel=\"noopener\"><span>Figure&nbsp;4<\/span><\/a>).<\/p>\n<p><!--fig ft0--><!--fig mode=article f1--><\/p>\n<div class=\"fig iconblock whole_rhythm\" id=\"fig4\" co-legend-rid=\"lgnd_fig4\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig4\/\" target=\"figure\" rid-figpopup=\"fig4\" rid-ob=\"ob-fig4\" rel=\"noopener\"><!--fig\/graphic|fig\/alternatives\/graphic mode=\"anchored\" m1--><\/a><\/p>\n<div class=\"figure\" data-largeobj=\"\" data-largeobj-link-rid=\"largeobj_idm140427038669008\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig4\/\" target=\"figure\" rid-figpopup=\"fig4\" rid-ob=\"ob-fig4\" rel=\"noopener\"><\/a><a class=\"inline_block ts_canvas\" href=\"\/core\/lw\/2.0\/html\/tileshop_pmc\/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&amp;p=PMC3&amp;id=6488769_gr4.jpg\" target=\"tileshopwindow\" rel=\"noopener\"><\/p>\n<div class=\"ts_bar small\" title=\"Click on image to zoom\"><\/div>\n<p><img decoding=\"async\" loading=\"lazy\" alt=\"An external file that holds a picture, illustration, etc.\nObject name is gr4.jpg\" title=\"Click on image to zoom\" class=\"tileshop\" src=\"https:\/\/hho-bulgaria.com\/wp-content\/uploads\/2024\/01\/gr4.jpg\"><\/a><\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm140427038669008\" style=\"display: none;\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig4\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"icnblk_cntnt\" id=\"lgnd_fig4\">\n<div><a class=\"figpopup\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig4\/\" target=\"figure\" rid-figpopup=\"fig4\" rid-ob=\"ob-fig4\" rel=\"noopener\">Figure&nbsp;4<\/a><\/div>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Radiographic Differences Between Groups<\/p>\n<p>Axial T2 images <strong>(A)<\/strong> were assessed for radiographically apparent injuries <strong>(B)<\/strong>, which were outlined as moderate <strong>(green)<\/strong> or severe <strong>(red)<\/strong> on a voxel-per-voxel basis. These areas of injury were corroborated by review of apparent diffusion coefficient mapping <strong>(C)<\/strong>, which were similarly outlined <strong>(D)<\/strong>. <strong>(E)<\/strong> Areas of injury were rendered in 3 dimensions and overlaid onto an image of the brain to provide a visual image of the differences in the volume of cranial injury. Data were based on brain MRI of 8 swine in the hydrogen-treated group and 6 in the control group (2 swine allocated to the control group died from refractory seizures and could not survive to day 3). <strong>(F)<\/strong> H<sub>2<\/sub>-treated animals exhibited a significantly lower volume of injury than did control animals (Student <em>t<\/em>-test: p&nbsp;= 0.0463). The <strong>line<\/strong> represents median, <strong>boxes<\/strong> are interquartile ranges, and <strong>error bars<\/strong> are minimum and maximum values.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"sec2.4\" class=\"sec sec-last\">\n<h3 id=\"sec2.4title\">Neuropathology<\/h3>\n<p id=\"p0110\" class=\"p p-first-last\">Regions of radiographically apparent injury correlated well with histologically apparent injury, with a predominance of injury in&nbsp;the frontal cortex. As a group, H<sub>2<\/sub>-treated swine exhibited significantly lower histologic injury scores than did controls (p&nbsp;= 0.0044) (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig5\/\" target=\"figure\" class=\"fig-table-link figpopup\" rid-figpopup=\"fig5\" rid-ob=\"ob-fig5\" co-legend-rid=\"lgnd_fig5\" rel=\"noopener\"><span>Figure&nbsp;5<\/span><\/a>), with a predominance of injury in the frontal cortex. There was no evidence of thalamic injury in this model.<\/p>\n<p><!--fig ft0--><!--fig mode=article f1--><\/p>\n<div class=\"fig iconblock whole_rhythm\" id=\"fig5\" co-legend-rid=\"lgnd_fig5\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig5\/\" target=\"figure\" rid-figpopup=\"fig5\" rid-ob=\"ob-fig5\" rel=\"noopener\"><!--fig\/graphic|fig\/alternatives\/graphic mode=\"anchored\" m1--><\/a><\/p>\n<div class=\"figure\" data-largeobj=\"\" data-largeobj-link-rid=\"largeobj_idm140427040713728\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig5\/\" target=\"figure\" rid-figpopup=\"fig5\" rid-ob=\"ob-fig5\" rel=\"noopener\"><\/a><a class=\"inline_block ts_canvas\" href=\"\/core\/lw\/2.0\/html\/tileshop_pmc\/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&amp;p=PMC3&amp;id=6488769_gr5.jpg\" target=\"tileshopwindow\" rel=\"noopener\"><\/p>\n<div class=\"ts_bar small\" title=\"Click on image to zoom\"><\/div>\n<p><img decoding=\"async\" loading=\"lazy\" alt=\"An external file that holds a picture, illustration, etc.\nObject name is gr5.jpg\" title=\"Click on image to zoom\" class=\"tileshop\" src=\"https:\/\/hho-bulgaria.com\/wp-content\/uploads\/2024\/01\/gr5.jpg\"><\/a><\/div>\n<div class=\"largeobj-link align_right\" id=\"largeobj_idm140427040713728\" style=\"display: none;\"><a target=\"object\" rel=\"noopener\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig5\/?report=objectonly\">Open in a separate window<\/a><\/div>\n<div class=\"icnblk_cntnt\" id=\"lgnd_fig5\">\n<div><a class=\"figpopup\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/figure\/fig5\/\" target=\"figure\" rid-figpopup=\"fig5\" rid-ob=\"ob-fig5\" rel=\"noopener\">Figure&nbsp;5<\/a><\/div>\n<p><!--caption a7--><\/p>\n<div class=\"caption\">\n<p>Histopathologic Differences Between Groups<\/p>\n<p>Regions of radiographically apparent injury <strong>(A) (arrows)<\/strong> correlated well with histologically apparent injury <strong>(B)<\/strong>, shown here by fluorescence microscopy (original magnification:&nbsp;\u00d71, using a Rhodamine filter). Neuronal injury was scored between 0 (normal) and 5 (severe neuronal injury, necrosis) for each region through identification of hypereosinophilic and\/or apoptotic neurons by using both light <strong>(C)<\/strong> and fluorescence <strong>(D)<\/strong> microscopy (original magnification:&nbsp;\u00d760; bars&nbsp;= 50 \u03bcm). <strong>Open arrows<\/strong> = hypereosinophilic and apoptotic neurons. <strong>(E)<\/strong> As a group, hydrogen-treated swine exhibited significantly lower histologic injury scores than controls (2-way repeated measures ANOVA according to Sidak&#8217;s test results: p&nbsp;= 0.0044). Data are based on histopathology for 8 swine in the hydrogen-treated group and 6 in the control group (2&nbsp;swine allocated to the control group died from refractory seizures and did not survive to day 3). Data are means; error bars are SEM.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"sec3\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec3title\">Discussion<\/h2>\n<p id=\"p0115\" class=\"p p-first\">We have shown that the perioperative administration of 2.40% H<sub>2<\/sub> is safe and diminishes neurologic injury in an experimental model of circulatory arrest. Although the combination of temperature and duration of circulatory arrest used is not used clinically, the model did successfully establish the degree of neurologic injury manifested in the most severely affected neonates, including perioperative seizures and radiographically apparent injury. In that setting, the perioperative administration of H<sub>2<\/sub> improved clinical neurologic scores, decreased serum markers of brain injury, decreased radiographically apparent volumes of brain injury, and lessened the degree of histopathologic injury. In addition, H<sub>2<\/sub>-treated swine exhibited a significantly lower concentration of serum creatinine during the survival period, suggesting that hydrogen may diminish the effects of renal ischemia. Notably, there were minimal differences between groups in injury measures of cardiac performance, such as venous oxyhemoglobin saturation. This may be because, in essence, animals underwent a 75-min period of cardioplegic aortic cross-clamping, an ischemic insult that is known to be well tolerated.<\/p>\n<p id=\"p0120\">This work adds to a growing body of preclinical studies supporting the therapeutic efficacy of inhalational H<sub>2<\/sub> gas. As mentioned previously, inhalational H<sub>2<\/sub> gas has been shown to diminish the volume of&nbsp;brain injury in rodent models of middle cerebral artery occlusion <a href=\"#bib21\" rid=\"bib21\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(21)<\/a> and asphyxial cardiac arrest <a href=\"#bib23\" rid=\"bib23\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(23)<\/a>. H<sub>2<\/sub> inhalation has also been shown to decrease cellular injury and improve post-ischemic organ function in several animal models. For example, the administration of 1.3% H<sub>2<\/sub> in dogs for 6 h following a 90-min occlusion of the left anterior descending artery resulted in a&nbsp;50% reduction in infarct size <a href=\"#bib29\" rid=\"bib29\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(29)<\/a>. A similarly protective effect has been shown following experimental ischemia-reperfusion injury in liver <a href=\"#bib30\" rid=\"bib30\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(30)<\/a>, lung <a href=\"#bib31\" rid=\"bib31\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(31)<\/a>, heart <a href=\"#bib32\" rid=\"bib32\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(32)<\/a>, and small intestine <a href=\"#bib33\" rid=\"bib33\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(33)<\/a> and&nbsp;in models of septic shock <a href=\"#bib34\" rid=\"bib34\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(34)<\/a>. Still other studies have examined the intravenous administration of H<sub>2<\/sub>-saturated saline <a href=\"#bib35\" rid=\"bib35\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(35)<\/a> and the oral administration of H<sub>2<\/sub> in tablet or water form <a href=\"#bib36\" rid=\"bib36\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(36)<\/a>, although the serum concentration achieved by the oral route is orders of&nbsp;magnitude lower than that in the inhalational route&nbsp;<a href=\"#bib37\" rid=\"bib37\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(37)<\/a>.<\/p>\n<p id=\"p0125\">Recently, a series of bold first-in-human studies of inhalational H<sub>2<\/sub> gas has been described. The first study <a href=\"#bib38\" rid=\"bib38\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(38)<\/a> was a case series describing the administration of 2% H<sub>2<\/sub> in 5 mechanically ventilated survivors of witnessed out-of-hospital cardiac arrest, which found that 4 of 5 patients exhibited favorable neurologic function (cerebral performance category 1)&nbsp;at hospital discharge. There were no environmental hazards reported. The second study <a href=\"#bib39\" rid=\"bib39\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(39)<\/a> describes the&nbsp;face mask administration of 1.3% H<sub>2<\/sub> in 10 adults (plus 10 controls) undergoing percutaneous coronary reperfusion for ST-segment elevation myocardial infarction, finding that H<sub>2<\/sub> significantly improved ejection fraction at 6-month follow-up examination <a href=\"#bib39\" rid=\"bib39\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(39)<\/a>. A third study <a href=\"#bib40\" rid=\"bib40\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(40)<\/a> described 25 patients (plus&nbsp;25&nbsp;controls) who presented with acute mild-to-moderately severe stroke, who underwent inhalation of 3% H<sub>2<\/sub> gas through face masks for 1 h twice per day for 7 days, which resulted in significant improvements in U.S. National Institutes&nbsp;of Health Stroke Scale scores and volumes of cerebral infarction by diffusion-weighted MRI imaging <a href=\"#bib40\" rid=\"bib40\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(40)<\/a>.<\/p>\n<p id=\"p0130\" class=\"p\">The application of H<sub>2<\/sub> administration in infants undergoing CPB is attractive for several reasons. First, it appears to be safe and easy to use. The dose tested here (2.4%) is a nonflammable gas mixture, even when mixed with balance (i.e., 97.6%) oxygen; hydrogen concentrations above 4% are known to be flammable. Following due diligence, we were able to attach these source gases were directly to the anesthesia machine and mechanical ventilator, and did not note any adverse effects on the delivery of anesthetic gas or on the function of either device. This represents an improvement on prior delivery techniques (which add a hydrogen-nitrogen mixture to inspiratory gas following passage through the ventilator) <a href=\"#bib38\" rid=\"bib38\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(38)<\/a> in several ways. The setup described in the present study ensured delivery of a constant concentration of H<sub>2<\/sub> regardless of the patient\u2019s oxygen requirements. Administration of H<sub>2<\/sub> gas mixtures to the ventilator inlet would likely be required to treat infants due to their high bias flow and rapid respiratory rate, factors that would cause excessive dilution of even the most concentrated hydrogen-nitrogen mixture. Second, H<sub>2<\/sub> appears to be well tolerated at the doses tested. Consistent with prior reports <a href=\"#bib40\" rid=\"bib40\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">40<\/a>, <a href=\"#bib41\" rid=\"bib41\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">41<\/a>, we did not find that the administration of H<sub>2<\/sub> had a measurable effect on hemodynamics or lung function. In the future, it will be important to study the effects of more extended durations of exposure (e.g.,&nbsp;72 h continuously) on these endpoints. Third, the application of H<sub>2<\/sub> may be practically added to current therapies, including hypothermia. For these reasons, a clinical trial of perioperative H<sub>2<\/sub> administration in neonates at high risk for neurologic injury may be warranted.<\/p>\n<div id=\"sec3.1\" class=\"sec sec-last\">\n<h3 id=\"sec3.1title\">Study limitations<\/h3>\n<p id=\"p0135\" class=\"p p-first-last\">1) Although the newborn piglet has become an accepted model for the term neonate, we note that the maturity of myelination in these animals was approximately that of an 12-18 month old infant. 2) The protective effects of inhalational anesthetics and of intravenous sedatives (e.g. propofol) are well appreciated and may have affected the degree of neuronal injury, although the dosing was&nbsp;protocolized and equally applied to both groups.&nbsp;3)&nbsp;Because we did not perform electroencephalography, we are unable to comment on hydrogen\u2019s effect on subclinical seizure activity. 4)&nbsp;Although previously well-characterized, we did not&nbsp;quantify the arterial concentrations of hydrogen gas during administration. Based on prior work, we&nbsp;expect that&nbsp;the arterial concentration of 2.4% H2&nbsp;(which was&nbsp;a certified gas mixture and therefore the concentration was independently verified) in mechanically ventilated swine would reach a plateau between 5-10 \u00b5M\/l within 20 min of inhalation <a href=\"#bib41\" rid=\"bib41\" class=\" bibr popnode\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">(41)<\/a>. The number of animals included in each group&nbsp;was small, such that less common adverse effects of hydrogen administration may not have been detected. A properly powered safety study is warranted.<\/p>\n<\/div>\n<\/div>\n<div id=\"sec4\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"sec4title\">Conclusions<\/h2>\n<p id=\"p0140\" class=\"p p-first-last\">In a small series of neonatal swine, the perioperative administration of inhalational H<sub>2<\/sub>&nbsp;gas diminishes neurologic injury following experimental circulatory arrest.<\/p>\n<div class=\"boxed-text-box whole_rhythm hide-overflow\" id=\"dtbox1\">\n<h3 id=\"dtbox1title\">Perspectives<\/h3>\n<p id=\"p0145\"><strong>COMPETENCY IN MEDICAL KNOWLEDGE:<\/strong> The use of inhaled hydrogen gas to diminish ischemic injury has been applied successfully in several rodent models and was recently described in humans following stroke, acute myocardial infarction, and cardiac arrest. A demonstration of&nbsp;safety in healthy volunteers is warranted, followed by a prospective study of hydrogen inhalation during congenital heart surgery and other clinical scenarios.<\/p>\n<p id=\"p0150\"><strong>TRANSLATIONAL OUTLOOK:<\/strong> The favorable side effect profile and ease of administration make hydrogen a potentially appealing ancillary therapy.<\/p>\n<\/div>\n<\/div>\n<div id=\"ack0010\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"ack0010title\">Acknowledgments<\/h2>\n<div class=\"sec\">\n<p>The authors thank veterinary staff Cara Pimental, Madeleine Woomer, and Hugh Simonds; clinical perfusion staff Greg Matte, Kevin Connor, Natalie Toutenel, and Molly Bryant; overnight nursing staff Jay Hartford, Danielle Healey, and Stephanie Pietrafitta; clinical radiology staff Peter Morriss and Joseph Zmuda; and feeding volunteers Abigail Moore, Lindsay Thomson, Katherine Black, Andrew Lock, Jemima Lamothe, Yifeng Peng, Raymond Seekell, and Cameron Russell. The authors also thank Jie Zhu for performing GFAP assays; institutional safety officer Chad Pires, Boston Fire Department; and Centers for Disease Control and Prevention consultant Isaac Zlochower for assistance with the technical implementation of this work.<\/p>\n<\/div>\n<\/div>\n<div id=\"fn-group-a.k.d\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"fn-group-a.k.dtitle\">Footnotes<\/h2>\n<p><!--back\/fn-group--><\/p>\n<div class=\"fm-sec half_rhythm small\">\n<p class=\"fn sec\" id=\"d31e165\">\n<p id=\"ntpara0010\" class=\"p p-first-last\">Dr. Kheir is supported by American Heart Association grant 15GRNT25700161; and by philanthropic donations from the Hess Family Cardiac Innovation Fund, the Furber Family Innovative Therapies Fund, and Lindsay Bartels (a donor who provided some financial support for the study). Dr. Everett is a consultant for Immunarray LLC; and holds patents through Johns Hopkins University assigned to Immunarray, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.<\/p>\n<\/p>\n<p class=\"fn sec\" id=\"d31e168\">\n<p id=\"ntpara0015\" class=\"p p-first-last\">All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors\u2019 institutions and U.S. Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the <em>JACC<\/em>: <em>Basic to Translational Science<\/em><a href=\"http:\/\/www.basictranslational.onlinejacc.org\/content\/instructions-authors\" data-ga-action=\"click_feat_suppl\" ref=\"reftype=extlink&amp;article-id=6488769&amp;issue-id=333532&amp;journal-id=3485&amp;FROM=Article%7CBody&amp;TO=External%7CLink%7CURI\" target=\"_blank\" rel=\"noopener\">author instructions page<\/a>.<\/p>\n<\/p>\n<\/div>\n<\/div>\n<div id=\"appsec1\" class=\"tsec bk-sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"appsec1title\">Appendix<\/h2>\n<p><!--\/article\/back\/sec\/--><\/p>\n<div class=\"sec suppmat\" id=\"mmc1\"><!--caption a9--><strong>Supplemental Figures&nbsp;S1\u2013S8 and Supplemental Table&nbsp;1:<\/strong><\/p>\n<div class=\"sup-box half_rhythm\" id=\"media-a.k.b.b.a.b\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6488769\/bin\/mmc1.pdf\" data-ga-action=\"click_feat_suppl\">Click here to view.<\/a><sup>(1.2M, pdf)<\/sup><\/div>\n<\/div>\n<\/div>\n<div id=\"cebib0010\" class=\"tsec sec\">\n<div class=\"goto jig-ncbiinpagenav-goto-container\"><a class=\"tgt_dark page-toc-label jig-ncbiinpagenav-goto-heading\" href=\"#\" title=\"Go to other sections in this page\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Go to:<\/a><\/div>\n<h2 class=\"head no_bottom_margin ui-helper-clearfix\" id=\"cebib0010title\">References<\/h2>\n<div class=\"ref-list-sec sec\" id=\"reference-list\">\n<div class=\"ref-cit-blk half_rhythm\" id=\"bib1\">1. <span class=\"element-citation\" id=\"sref1\">Algra S.O., Jansen N.J.G., van der Tweel I. 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A&nbsp;basic study on molecular hydrogen (H2) inhalation in&nbsp;acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level. <span><span class=\"ref-journal\">Medical Gas Research. <\/span>2012;<span class=\"ref-vol\">2<\/span>:1.<\/span> <span class=\"nowrap\">[<a class=\"int-reflink\" href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3457852\/\">PMC free article<\/a>]<\/span> [<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/22916706\" ref=\"reftype=pubmed&amp;article-id=6488769&amp;issue-id=333532&amp;journal-id=3485&amp;FROM=Article%7CCitationRef&amp;TO=Entrez%7CPubMed%7CRecord\">PubMed<\/a>] <span class=\"nowrap\">[<a href=\"https:\/\/scholar.google.com\/scholar_lookup?journal=Medical+Gas+Research&amp;title=A&nbsp;basic+study+on+molecular+hydrogen+(H2)+inhalation+in&nbsp;acute+cerebral+ischemia+patients+for+safety+check+with+physiological+parameters+and+measurement+of+blood+H2+level&amp;author=H.+Ono&amp;author=Y.+Nishijima&amp;author=N.+Adachi&amp;volume=2&amp;publication_year=2012&amp;pages=1&amp;pmid=22273079&amp;\" target=\"_blank\" rel=\"noopener noreferrer\" ref=\"reftype=other&amp;article-id=6488769&amp;issue-id=333532&amp;journal-id=3485&amp;FROM=Article%7CCitationRef&amp;TO=Content%20Provider%7CLink%7CGoogle%20Scholar\" role=\"button\" aria-expanded=\"false\" aria-haspopup=\"true\">Google Scholar<\/a>]<\/span><\/span><\/div>\n<\/div>\n<\/div>\n<div style=\"display: none; width: 200px; top: -100px; left: -100px;\" aria-live=\"assertive\" aria-hidden=\"true\" class=\"ui-helper-reset ui-ncbipopper-wrapper ui-ncbilinksmenu\">\n<ul id=\"ui-ncbiinpagenav-2\">\n<li><a href=\"#abs0015title\">Visual Abstract<\/a><\/li>\n<li><a href=\"#abs0020title\">Highlights<\/a><\/li>\n<li><a href=\"#abs0010title\">Summary<\/a><\/li>\n<li><a href=\"#sec1title\">Methods<\/a><\/li>\n<li><a href=\"#sec2title\">Results<\/a><\/li>\n<li><a href=\"#sec3title\">Discussion<\/a><\/li>\n<li><a href=\"#sec4title\">Conclusions<\/a><\/li>\n<li><a href=\"#ack0010title\">Acknowledgments<\/a><\/li>\n<li><a href=\"#fn-group-a.k.dtitle\">Footnotes<\/a><\/li>\n<li><a href=\"#appsec1title\">Appendix<\/a><\/li>\n<li><a href=\"#cebib0010title\">References<\/a><\/li>\n<\/ul>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Perioperatively Inhaled Hydrogen Gas Diminishes Neurologic Injury Following Experimental Circulatory Arrest in Swine<\/p>\n","protected":false},"author":1,"featured_media":17899,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[130],"tags":[],"disease":[844],"body-organ":[1019],"applications":[679],"test_subjects":[1524],"report-topic":[1277],"class_list":["post-26992","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-hydrogen-health","disease-surgery-transplantation-2","body-organ-brain-2","applications-inhalation-2","test_subjects-pig-2","report-topic-cardiopulmonary-bypass-2"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>H2 Gas Reduces Neurologic Injury in Circulatory Arrest<\/title>\n<meta name=\"description\" content=\"Perioperatively Inhaled Hydrogen Gas Diminishes Neurologic Injury Following Experimental Circulatory Arrest in Swine\" 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