{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:17:20Z","timestamp":1787062640357,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010890","name":"Chinese Government Scholarship","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Cardioprotective strategies against ischemia-reperfusion injury (IRI) that remain effective in the clinical arena need to be developed. Therefore, maintained efficacy of cardioprotective strategies in the presence of drugs routinely used clinically (e.g., opiates, benzodiazepines, P2Y\n                    <jats:sub>12<\/jats:sub>\n                    antagonist, propofol) need to be identified in preclinical models.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Here, we examined the efficacy of promising cardioprotective compounds [fingolimod (Fingo), empagliflozin (Empa), melatonin (Mela) and nicotinamide riboside (NR)] administered i.v. as bolus before start ischemia. Infarct size as percentage of the area of risk (IS%) was determined following 25 min of left ascending coronary (LAD) ischemia and 2 h of reperfusion in a fentanyl-midazolam anesthetized IRI rat model. Plasma lactate dehydrogenase (LDH) activity at 30 min reperfusion was determined as secondary outcome parameter. Following pilot dose-response experiments of each compound (3 dosages,\n                    <jats:italic>n<\/jats:italic>\n                    = 4\u20136 animals per dosage), potential cardioprotective drugs at the optimal observed dosage were subsequently tested alone or in combination (\n                    <jats:italic>n<\/jats:italic>\n                    = 6\u20138 animals per group). The effective treatment was subsequently tested in the presence of a P2Y\n                    <jats:sub>12<\/jats:sub>\n                    antagonist (cangrelor;\n                    <jats:italic>n<\/jats:italic>\n                    = 6\/7) or propofol aesthesia (\n                    <jats:italic>n<\/jats:italic>\n                    = 6 both groups).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Pilot studies suggested potential cardioprotective effects for 50 mg\/kg NR (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.005) and 500 \u03bcg\/kg melatonin (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.12), but not for Empa or Fingo. Protection was subsequently tested in a new series of experiments for solvents, NR, Mela and NR+Mela. Results demonstrated that only singular NR was able to reduce IS% (30 \u00b1 14 vs. 60 \u00b1 16%,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.009 vs. control). Mela (63 \u00b1 18%) and NR+Mela (47 \u00b1 15%) were unable to significantly decrease IS%. NR still reduced IS in the presence of cangrelor (51 \u00b1 18 vs. 71 \u00b1 4%,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.016 vs. control), but lost protection in the presence of propofol anesthesia (62 \u00b1 16 vs. 60 \u00b1 14%,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.839 vs. control). LDH activity measurements supported all IS% results.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    This observational study suggests that NR is a promising cardioprotective agent to target cardiac ischemia-reperfusion injury in clinical conditions employing opioid agonists, benzodiazepines and platelet P2Y\n                    <jats:sub>12<\/jats:sub>\n                    inhibitors, but not propofol.\n                  <\/jats:p>","DOI":"10.3389\/fcvm.2021.712478","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T11:55:34Z","timestamp":1630670134000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Cardioprotecive Properties of Known Agents in Rat Ischemia-Reperfusion Model Under Clinically Relevant Conditions: Only the NAD Precursor Nicotinamide Riboside Reduces Infarct Size in Presence of Fentanyl, Midazolam and Cangrelor, but Not Propofol"],"prefix":"10.3389","volume":"8","author":[{"given":"Yang","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Phelp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Bakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianne","family":"Nederlof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus W.","family":"Hollmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coert 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