• Uwe M Fischer, Oliver Klass, Ulrike Stock, Jerry Easo, Hans J Geissler, Juergen H Fischer, Wilhelm Bloch, and Uwe Mehlhorn.
• Department of Cardiothoracic Surgery1, University of Cologne, Cologne, Germany.
• Eur J Cardiothorac Surg. 2003 Jun 1;23(6):984-90.

ObjectiveMyocardial ischemia-reperfusion is associated with free radical-mediated injury and may be involved in cardiac apoptosis. The purpose of our study was to investigate (1) if cardioplegia-induced ischemia-reperfusion initiates cardiac apoptosis signal pathway, and (2) if this is mediated by free radicals.MethodsWe subjected 13 pigs (56+/-10 kg) to 1 h of cold crystalloid cardioplegic arrest (CA) on cardiopulmonary bypass (CPB), and collected five transmural LV biopsies: prior to CPB (baseline), at 60 min CA, at 15 and 30 min reperfusion on CPB, and at 120 min post CPB. Two additional pigs were subjected to CPB but not CA and two further pigs were neither subjected to CPB nor CA and served as sham-operated time controls. LV specimens were cut at 7 microm and immunocytochemically stained against active caspase-3 and 85 kDa poly(ADP-ribose) polymerase (PARP) as apoptosis signal-pathway key enzymes, nitrotyrosine as indicator for peroxynitrite (ONOO(-))-mediated tissue injury, and 8-iso-prostaglandin-F(2)alpha as indicator for oxygen free radical-mediated lipid peroxidation. Specimen were assessed using a scale of 0 (negative) to 3 (highly positive), and cardiomyocytes were quantitatively investigated using TV densitometry.ResultsAt 60 min CA, caspase-3 was increased by 9.2+/-3.7 gray units and remained on this level until 2 h post CPB (PConclusionsOur data show that CA initiates apoptosis signal-pathway in myocardial endothelium and myocytes; however, this did not result in apoptotic cell death as we did not find PARP cleavage. Further, the data suggest that CA-induced apoptosis signal pathway activation is not mediated by free radicals as caspase-3 activation preceded both nitrotyrosine and 8-iso-prostaglandin-F(2)alpha formation.

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