Controlled reperfusion after hypothermic heart preservation inhibits mitochondrial permeability transition-pore opening and enhances functional recovery.
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 cmH(2)O) and 2) reperfusion with normal pressure (NP = 100 cmH(2)O). Cardiac function was assessed during reperfusion using the Langendorff model. Mitochondria were isolated, and the Ca(2+) 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.
Bopassa
J C
JC
EMI-U 0226, Laboratoire de Physiologie, Faculté de Médecine Lyon-Nord, 8, Ave. Rockefeller, 69373 LYON Cedex 08, France.
Vandroux
David
D
Ovize
M
M
Ferrera
R
R
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000032:analysis; D007036:Hypothermia, Induced; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008929:Mitochondria, Heart / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D000083162:Mitochondrial Permeability Transition Pore; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000379:methods*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010539:Permeability; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008315:Malondialdehyde; D045304:Cytochromes c; D053148:Caspase 3; D002118:Calcium