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

J. C. Bopassa, David Vandroux, M. Ovize, R. Ferrera

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13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)H2265-H2271
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number5
DOIs
StatePublished - Nov 24 2006
Externally publishedYes

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Keywords

  • Apoptosis
  • Mitochondria

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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