BACKGROUND AND AIM OF STUDY: Hypothermic preservation (PRES) of donor hearts is limited to 12-14 hours for complete functional recovery after reperfusion. In a canine heterotopic heart transplant model, 50% to 60% functional recovery returned after 18 hours of PRES with University of Wisconsin (UW) solution. Concomitant with functional changes were marked increases in apoptotic cells at 2 (2.69%) and 6 (5.98%) hours of reperfusion with a concomitant decrease in lamin B1 (2% and 7.6%, respectively) with no evidence of necrotic cells. These results suggested that blockade of apoptosis may prolong myocardial viability during PRES and reperfusion. METHODS: Donor hearts were subjected to 18 and 24 hours of PRES (2 degrees C to 4 degrees C) with and without cyclosporine A (CyS) treatment (apoptosis blocker). CyS was given to the donor animal (10 mg/kg), in the PRES solution (10(-5) mol/L), slowly infused during the PRES period (1 mL/min), and also to the recipient animal (2.5 mg/kg). RESULTS: After 18 hours of PRES with CyS, function returned to 100% within 1 hour and stayed at this level throughout a 6-hour recovery period. Apoptotic myocytes were reduced (55%) after 18 hours PRES with CyS treatment, and 6-hour reperfusion lamin B1 was reduced to only 3.7%. Twenty-four hour PRES in UW resulted in no functional recovery. However, after CyS treatment, functional recovery returned to 100% after 4 hours of reperfusion. Adenosine triphosphate (ATP) and creatine phosphate (CP) concentrations were surprisingly the same with or without CyS treatment at 18 hours and lower with 24 hours. CONCLUSIONS: Use of CyS in the PRES solution prolongs myocardial viability during donor heart PRES. The mechanism of action may be associated with the mitochondrial permeability transition (MPT) pore via cyclophilin D binding.
BACKGROUND AND AIM OF STUDY: Hypothermic preservation (PRES) of donor hearts is limited to 12-14 hours for complete functional recovery after reperfusion. In a canine heterotopic heart transplant model, 50% to 60% functional recovery returned after 18 hours of PRES with University of Wisconsin (UW) solution. Concomitant with functional changes were marked increases in apoptotic cells at 2 (2.69%) and 6 (5.98%) hours of reperfusion with a concomitant decrease in lamin B1 (2% and 7.6%, respectively) with no evidence of necrotic cells. These results suggested that blockade of apoptosis may prolong myocardial viability during PRES and reperfusion. METHODS:Donor hearts were subjected to 18 and 24 hours of PRES (2 degrees C to 4 degrees C) with and without cyclosporine A (CyS) treatment (apoptosis blocker). CyS was given to the donor animal (10 mg/kg), in the PRES solution (10(-5) mol/L), slowly infused during the PRES period (1 mL/min), and also to the recipient animal (2.5 mg/kg). RESULTS: After 18 hours of PRES with CyS, function returned to 100% within 1 hour and stayed at this level throughout a 6-hour recovery period. Apoptotic myocytes were reduced (55%) after 18 hours PRES with CyS treatment, and 6-hour reperfusion lamin B1 was reduced to only 3.7%. Twenty-four hour PRES in UW resulted in no functional recovery. However, after CyS treatment, functional recovery returned to 100% after 4 hours of reperfusion. Adenosine triphosphate (ATP) and creatine phosphate (CP) concentrations were surprisingly the same with or without CyS treatment at 18 hours and lower with 24 hours. CONCLUSIONS: Use of CyS in the PRES solution prolongs myocardial viability during donor heart PRES. The mechanism of action may be associated with the mitochondrial permeability transition (MPT) pore via cyclophilin D binding.
Authors: Paolo Stassano; Luigi Di Tommaso; Mario Monaco; Generoso Mastrogiovanni; Antonino Musumeci; Antonio Contaldo; Paolo Pepino Journal: World J Surg Date: 2010-04 Impact factor: 3.352