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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/H1654    most recent 01378.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Gomez, L. Articles by Ovize, M. Search for Related Content PubMed PubMed Citation Articles by Gomez, L. Articles by Ovize, M.

Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice

¹Institut National de la Santé et de la Recherche Médicale E 0226, Université Claude Bernard Lyon I, Lyon, and ²Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon Cedex, France; and ³DebioPharm S.A., Lausanne, Switzerland

Submitted 18 December 2006 ; accepted in final form 1 June 2007

Inhibition of mitochondrial permeability transition pore (mPTP) opening by cyclosporin A or ischemic postconditioning attenuates lethal reperfusion injury. Its impact on major post-myocardial infarction events, including worsening of left ventricular (LV) function and death, remains unknown. We sought to determine whether pharmacological or postconditioning-induced inhibition of mPTP opening might improve functional recovery and survival following myocardial infarction in mice. Anesthetized mice underwent 25 min of ischemia and 24 h (protocol 1) or 30 days (protocol 2) of reperfusion. At reperfusion, they received no intervention (control), postconditioning (3 cycles of 1 min ischemia-1 min reperfusion), or intravenous injection of the mPTP inhibitor Debio-025 (10 mg/kg). At 24 h of reperfusion, mitochondria were isolated from the region at risk for assessment of the Ca²⁺ retention capacity (CRC). Infarct size was measured by triphenyltetrazolium chloride staining. At 30 days of reperfusion, mortality and LV contractile function (echocardiography) were evaluated. Postconditioning and Debio-025 significantly improved Ca²⁺ retention capacity (132 ± 13 and 153 ± 31 vs. 53 ± 16 nmol Ca²⁺/mg protein in control) and reduced infarct size to 35 ± 4 and 32 ± 7% of area at risk vs. 61 ± 6% in control (P < 0.05). At 30 days, ejection fraction averaged 74 ± 6 and 77 ± 6% in postconditioned and Debio-025 groups, respectively, vs. 62 ± 12% in the control group (P < 0.05). At 30 days, survival was improved from 58% in the control group to 92 and 89% in postconditioned and Debio-025 groups, respectively. Inhibition of mitochondrial permeability transition at reperfusion improves functional recovery and mortality in mice.

ischemic postconditioning; left ventricular contractile function; mitochondrial permeability transition pore

This article has been cited by other articles:

				L. Gomez, M. Paillard, H. Thibault, G. Derumeaux, and M. Ovize Inhibition of GSK3{beta} by Postconditioning Is Required to Prevent Opening of the Mitochondrial Permeability Transition Pore During Reperfusion Circulation, May 27, 2008; 117(21): 2761 - 2768. [Abstract] [Full Text] [PDF]