Extending myocardial viability during heart preservation with cyclosporineA

Background and Aim of Study. Hypothermic preservation (PRES) of donor heart s is limited to 12-14 hours for complete functional recovery after reperfus ion. In a ca. nine heterotopic heart transplant model, 50% to 60% functiona l recovery returned after 18 hours of PRES with University of Wisconsin (UW ) solution. Concomitant with functional changes were marked increases in ap optotic cells at 2 (2.69%) and 6 (5.98%) hours of reperfusion with a concom itant decrease in lamin B-1 (2% and 7.6%, respectively) with no evidence of necrotic cells. These results suggested that blockade of apoptosis may pro long myocardial viability during PRES and reperfusion. Methods: Donor heart s were subjected to 18 and 24 hours of PRES (2 degreesC to 4 degreesC) with and without cyclosporine A (CyS) treatment (apoptosis blocker). CyS was gi ven to the donor animal (10 mg/kg), in the PRES solution (10(-5) mol/L), sl owly infused during the PRES period (1 mL/min), and also to the recipient a nimal (2.5 mg/kg). Results: After 18 hours of PRES with CyS, function retur ned to 100% within 1 hour and stayed at this level throughout a 6-hour reco very period. Apoptotic myocytes were reduced (55%) after 18 hours PRES with CyS treatment, and 6-hour reperfusion lamin B-1 was reduced to only 3.7%. Twenty-four hour PRES in UW resulted in no functional recovery. However, af ter CyS treatment, functional recovery returned to 100% after 4 hours of re perfusion. Adenosine triphosphate (ATP) and creatine phosphate (CP) concent rations were surprisingly the same with or without CyS treatment at 18 hour s and lower with 24 hours. Conclusions: Use of CyS in the PRES solution pro longs myocardial viability during donor heart PRES. The mechanism of action may be associated with the mitochondrial permeability transition (MPT) por e via cyclophilin D binding.