期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 293, 期 3, 页码 H1654-H1661出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01378.2006
关键词
ischemic postconditioning; left ventricular contractile function; mitochondrial permeability transition pore
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.
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