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Zofenopril is a unique\n                      <jats:styled-content style=\"fixed-case\">ACE<\/jats:styled-content>\n                      I that has been shown to increase hydrogen sulfide (H\n                      <jats:sub>2<\/jats:sub>\n                      S) bioavailability and nitric oxide (\n                      <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\n                      ) levels via bradykinin\u2010dependent signaling. Both H\n                      <jats:sub>2<\/jats:sub>\n                      S and\n                      <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\n                      exert cytoprotective and antioxidant effects. We examined zofenopril effects on H\n                      <jats:sub>2<\/jats:sub>\n                      S and\n                      <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\n                      bioavailability and cardiac damage in murine and swine models of myocardial ischemia\/reperfusion (\n                      <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\n                      \/R) injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Zofenopril (10\u00a0mg\/kg\n                      <jats:styled-content style=\"fixed-case\">PO<\/jats:styled-content>\n                      ) was administered for 1, 8, and 24\u00a0hours to establish optimal dosing in mice. Myocardial and plasma H\n                      <jats:sub>2<\/jats:sub>\n                      S and\n                      <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\n                      levels were measured along with the levels of H\n                      <jats:sub>2<\/jats:sub>\n                      S and\n                      <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\n                      enzymes (cystathionine \u03b2\u2010synthase, cystathionine \u03b3\u2010lyase, 3\u2010mercaptopyruvate sulfur transferase, and endothelial nitric oxide synthase). Mice received 8\u00a0hours of zofenopril or vehicle pretreatment followed by 45\u00a0minutes of ischemia and 24\u00a0hours of reperfusion. Pigs received placebo or zofenopril (30\u00a0mg\/daily orally) 7\u00a0days before 75\u00a0minutes of ischemia and 48\u00a0hours of reperfusion. Zofenopril significantly augmented both plasma and myocardial H\n                      <jats:sub>2<\/jats:sub>\n                      S and\n                      <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\n                      levels in mice and plasma H\n                      <jats:sub>2<\/jats:sub>\n                      S (sulfane sulfur) in pigs. Cystathionine \u03b2\u2010synthase, cystathionine \u03b3\u2010lyase, 3\u2010mercaptopyruvate sulfur transferase, and total endothelial nitric oxide synthase levels were unaltered, while phospho\u2010endothelial nitric oxide synthase\n                      <jats:sup>1177<\/jats:sup>\n                      was significantly increased in mice. Pretreatment with zofenopril significantly reduced myocardial infarct size and cardiac troponin I levels after\n                      <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\n                      \/R injury in both mice and swine. Zofenopril also significantly preserved ischemic zone endocardial blood flow at reperfusion in pigs after I\/R.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Zofenopril\u2010mediated cardioprotection during\n                      <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\n                      \/R is associated with an increase in H\n                      <jats:sub>2<\/jats:sub>\n                      S and\n                      <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\n                      signaling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.116.003531","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T06:10:42Z","timestamp":1505715042000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":67,"title":["Zofenopril Protects Against Myocardial Ischemia\u2013Reperfusion Injury by Increasing Nitric Oxide and Hydrogen Sulfide Bioavailability"],"prefix":"10.1161","volume":"5","author":[{"given":"Erminia","family":"Donnarumma","sequence":"first","affiliation":[{"name":"Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murtuza J.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Louisiana State University Health Sciences Center, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Rushing","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Scarborough","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Bradley","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea L.","family":"Organ","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazi N.","family":"Islam","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Polhemus","sequence":"additional","affiliation":[{"name":"Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Menarini Ricerche S.p.a., Preclinical Development, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Cirino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples \u201cFederico II\u201d, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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