{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:54:35Z","timestamp":1792652075737,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Therapeutic strategies for preventing paradoxical reperfusion injury after myocardial ischemia are limited. We tested whether central nervous system actions of leptin induce important protective effects on cardiac function and metabolism after myocardial ischemia\/reperfusion (I\/R) injury, the role of cardiac sympathetic innervation in mediating these effects, and whether there are major sex differences in the cardioprotective effects of chronic central nervous system leptin infusion.<\/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              Myocardial I\/R was induced by temporary ligation of the left descending coronary artery in male and female Wistar rats instrumented with intracerebroventricular cannula in the lateral ventricle. Vehicle or leptin (0.62\u2009\u03bcg\/h) infusion was started immediately after reperfusion and continued for 28\u2009days using osmotic minipumps connected to the intracerebroventricular cannula. Cardiac function was assessed by echocardiography, ventricular pressures, and exercise performance. Intracerebroventricular leptin treatment markedly attenuated cardiac dysfunction post\u2010I\/R as evidenced by improved ejection fraction (56.7\u00b11.9 versus 22.6%\u00b11.1%), maximal rate of left ventricle rise (11\u2009680\u00b12122 versus 5022\u00b1441\u2009mm\u2009Hg) and exercise performance (\u22124.2\u00b17.9 versus \u221268.2\u00b13.8 \u0394%) compared with vehicle\u2010treated rats. Intracerebroventricular leptin infusion reduced infarct size in females, but not males, when compared with ad\u2010lib fed or pair\u2010fed saline\u2010treated rats. Intracerebroventricular leptin treatment also increased cardiac NAD\n              <jats:sup>+<\/jats:sup>\n              \/NADH content (\u224810\u2010fold) and improved mitochondrial function when compared with vehicle treatment. Cervical ganglia denervation did not attenuate the cardiac protective effects of leptin after I\/R injury.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These data indicate that leptin, via its central nervous system actions, markedly improves overall heart function and mitochondrial metabolism after I\/R injury regardless of sex, effects that are largely independent of cardiac sympathetic innervation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027081","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T10:58:35Z","timestamp":1666868315000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Central Nervous System Actions of Leptin Improve Cardiac Function After Ischemia\u2013Reperfusion: Roles of Sympathetic Innervation and Sex Differences"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-7109","authenticated-orcid":false,"given":"Ana C. M.","family":"Omoto","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center Jackson MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussara M.","family":"do Carmo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center Jackson MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8529-4850","authenticated-orcid":false,"given":"Benjamin","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center Jackson 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MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Flynn","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center Jackson MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center Jackson MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5973-3071","authenticated-orcid":false,"given":"Alan J.","family":"Mouton","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center Jackson MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5781-1662","authenticated-orcid":false,"given":"Xuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center Jackson MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9867-5855","authenticated-orcid":false,"given":"John E.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center Jackson 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