6533b82afe1ef96bd128b7cb

RESEARCH PRODUCT

Controlled reperfusion after hypothermic heart preservation inhibits mitochondrial permeability transition-pore opening and enhances functional recovery.

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We investigated whether low-pressure reperfusion may attenuate postischemic contractile dysfunction, limits necrosis and apoptosis after a prolonged hypothermic ischemia, and inhibits mitochondrial permeability transition-pore (MPTP) opening. Isolated rats hearts ( n = 72) were exposed to 8 h of cold ischemia and assigned to the following groups: 1) reperfusion with low pressure (LP = 70 cmH2O) and 2) reperfusion with normal pressure (NP = 100 cmH2O). Cardiac function was assessed during reperfusion using the Langendorff model. Mitochondria were isolated, and the Ca2+resistance capacity (CRC) of the MPTP was determined. Malondialdehyde (MDA) production, caspase-3 activity, and cytochrome c were also assessed. We found that functional recovery was significantly improved in LP hearts with rate-pressure product averaging 30,380 ± 1,757 vs. 18,000 ± 1,599 mmHg/min in NP hearts ( P < 0.01). Necrosis, measured by triphenyltetrazolium chloride staining and creatine kinase leakage, was significantly reduced in LP hearts ( P < 0.01). The CRC was increased in LP heart mitochondria ( P < 0.01). Caspase-3 activity, cytochrome c release, and MDA production were reduced in LP hearts ( P < 0.001 and P < 0.01). This study demonstrated that low-pressure reperfusion after hypothermic heart ischemia improves postischemic contractile dysfunction and attenuates necrosis and apoptosis. This protection could be related to an inhibition of mitochondrial permeability transition.