{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:04:42Z","timestamp":1791281082941,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2002,2,1]],"date-time":"2002-02-01T00:00:00Z","timestamp":1012521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Myocardial depression can be demonstrated following administration of endotoxin. Proposed mechanisms of endotoxin-induced myocardial dysfunction include the release of proinflammatory mediators, focal myocardial ischemia, and the presence of activated leukocytes within the myocardium. Recently, myocardial caspase activation and mitochondria-related apoptotic events (i.e., release of cytochrome c) were demonstrated in the failing septic heart. Here, we tested the hypothesis that immunosuppressors, cyclosporin A and tacrolimus (FK 506), would improve inflammation, heart nuclear apoptosis, and myocardial dysfunction in endotoxin-treated rats. Myocardial contractility was assessed using an isolated heart preparation. Heart leukocyte infiltration was assessed by measurement of heart myeloperoxidase activity. Leukocyte activation was studied using the intravital microscopy of the mesenteric venule. Apoptosis was detected as myocardial DNA fragmentation, downstream caspase activation, and mitochondrial cytochrome c release. Both cyclosporin A and FK 506 reduced heart leukocyte sequestration and venular adhesion in endotoxin-treated rats. Cyclosporin A, which blocks mitochondrial cytochrome c release, was able to reduce endotoxin-induced myocardial end-stage nuclear apoptosis and heart dysfunction, whereas tacrolimus had no such effects. These effects could be related to the unique properties of cyclosporin A to act on mitochondria.<\/jats:p>","DOI":"10.1164\/ajrccm.165.4.2105084","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T14:57:41Z","timestamp":1365087461000},"page":"449-455","source":"Crossref","is-referenced-by-count":55,"title":["Protective Effects of Cyclosporin A from Endotoxin-induced Myocardial Dysfunction and Apoptosis in Rats"],"prefix":"10.1093","volume":"165","author":[{"given":"Harold","family":"Fauvel","sequence":"first","affiliation":[{"name":"INSERM U459, Facult\u00e9 de M\u00e9decine 1, EA 2689, CHRU and Universit\u00e9 de Lille 2, and D\u00e9partement de Physiologie, Facult\u00e9 de M\u00e9decine Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Marchetti","sequence":"additional","affiliation":[{"name":"INSERM U459, Facult\u00e9 de M\u00e9decine 1, EA 2689, CHRU and Universit\u00e9 de Lille 2, and D\u00e9partement de Physiologie, Facult\u00e9 de M\u00e9decine Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Obert","sequence":"additional","affiliation":[{"name":"INSERM U459, Facult\u00e9 de M\u00e9decine 1, EA 2689, CHRU and Universit\u00e9 de Lille 2, and D\u00e9partement de Physiologie, Facult\u00e9 de M\u00e9decine Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Joulain","sequence":"additional","affiliation":[{"name":"INSERM U459, Facult\u00e9 de M\u00e9decine 1, EA 2689, CHRU and Universit\u00e9 de Lille 2, and D\u00e9partement de Physiologie, Facult\u00e9 de M\u00e9decine Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Chopin","sequence":"additional","affiliation":[{"name":"INSERM U459, Facult\u00e9 de M\u00e9decine 1, EA 2689, CHRU and Universit\u00e9 de Lille 2, and D\u00e9partement de Physiologie, Facult\u00e9 de M\u00e9decine Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Formstecher","sequence":"additional","affiliation":[{"name":"INSERM U459, Facult\u00e9 de M\u00e9decine 1, EA 2689, CHRU and Universit\u00e9 de Lille 2, and D\u00e9partement de Physiologie, Facult\u00e9 de M\u00e9decine Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9mi","family":"Nevi\u00e8re","sequence":"additional","affiliation":[{"name":"INSERM U459, Facult\u00e9 de M\u00e9decine 1, EA 2689, CHRU and Universit\u00e9 de Lille 2, and D\u00e9partement de Physiologie, Facult\u00e9 de M\u00e9decine Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,2,15]]},"reference":[{"key":"2026031623142335800_B1","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1172\/JCI112135","article-title":"A circulating myocardial depressant substance in humans with septic shock. Septic shock patients with a reduced ejection fraction have a circulating factor that depresses in vitro myocardial cell performance.","volume":"76","author":"Parrillo","year":"1985","journal-title":"J Clin Invest"},{"key":"2026031623142335800_B2","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1084\/jem.169.3.823","article-title":"Endotoxin and tumor necrosis factor challenges in dogs simulate the cardiovascular profile of human septic shock.","volume":"169","author":"Natanson","year":"1989","journal-title":"J Exp Med"},{"key":"2026031623142335800_B3","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1378\/chest.97.1.126","article-title":"Right ventricular dysfunction and dilatation, similar to left ventricular changes, characterize the cardiac depression of septic shock in humans.","volume":"97","author":"Parker","year":"1990","journal-title":"Chest"},{"key":"2026031623142335800_B4","first-page":"181","article-title":"Molecular biology of septic 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synthase.","volume":"28","author":"Stein","year":"1996","journal-title":"J Mol Cell Cardiol"},{"key":"2026031623142335800_B8","first-page":"R577","article-title":"Tumor necrosis factor in the heart.","volume":"274","author":"Meldrum","year":"1998","journal-title":"Am J Physiol"},{"key":"2026031623142335800_B9","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1126\/science.1631560","article-title":"Negative inotropic effects of cytokines on the heart mediated by nitric oxide.","volume":"257","author":"Finkel","year":"1992","journal-title":"Science"},{"key":"2026031623142335800_B10","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1097\/00003246-199909000-00012","article-title":"Myocardial cell injury in septic shock.","volume":"27","author":"Turner","year":"1999","journal-title":"Crit Care Med"},{"key":"2026031623142335800_B11","first-page":"H1446","article-title":"Myocardial morphometric changes related to decreased contractility after 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transition.","volume":"426","author":"Petit","year":"1998","journal-title":"FEBS Lett"},{"key":"2026031623142335800_B32","first-page":"2033","article-title":"Apoptosis-associated derangement of mitochondrial function in cells lacking mitochondrial DNA.","volume":"56","author":"Marchetti","year":"1996","journal-title":"Cancer Res"},{"key":"2026031623142335800_B33","first-page":"205","article-title":"Anti-CD18 antibody attenuates neutropenia and alveolar capillary-membrane injury during gram-negative sepsis.","volume":"110","author":"Walsh","year":"1991","journal-title":"Surgery"},{"key":"2026031623142335800_B34","first-page":"G1051","article-title":"Neutrophil-induced liver cell injury in endotoxin shock is a CD11b\/CD18-dependent mechanism.","volume":"261","author":"Jaeschke","year":"1991","journal-title":"Am J Physiol"},{"key":"2026031623142335800_B35","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1152\/jappl.1992.73.4.1510","article-title":"Role of leukocyte CD11\/ CD18 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cyclosporin A and FK506 on ischemia\/reperfusion-induced neutrophil infiltration in the cat.","volume":"36","author":"Kubes","year":"1991","journal-title":"Dig Dis Sci"},{"key":"2026031623142335800_B39","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1161\/01.RES.87.9.731","article-title":"Calcineurin and beyond: cardiac hypertrophic signaling.","volume":"87","author":"Molkentin","year":"2000","journal-title":"Circ Res"},{"key":"2026031623142335800_B40","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1161\/01.RES.84.6.623","article-title":"Prevention of cardiac hypertrophy by calcineurin inhibition: hope or hype?","volume":"84","author":"Olson","year":"1999","journal-title":"Circ Res"},{"key":"2026031623142335800_B41","doi-asserted-by":"crossref","first-page":"5151","DOI":"10.1523\/JNEUROSCI.18-14-05151.1998","article-title":"Cyclosporin A, but not FK 506, protects mitochondria and neurons against hypoglycemic damage and implicates the mitochondrial permeability 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