Effects of diltiazem as an additive to St Thomas's Hospital cardioplegic solution in isolated neonatal and adult rabbit hearts

Abstract

The aim was to compare the protective efficacy of diltiazem as an additive to St Thomas's Hospital cardioplegic solution in isolated hearts from neonatal and adult rabbits. The relative responsiveness of the two age groups to diltiazem was first determined in Langendorff perfused hearts (n = 6 per group) by constructing concentration-response curves for the drug's negative inotropic effect. The IC20 and IC50 of diltiazem (the concentrations of diltiazem resulting in 20% or 50% reduction in developed pressure, respectively) were the doses subsequently included in the cardioplegic solution. Isolated working hearts (n = 8 per group) were perfused aerobically (37 degrees C) for 20 min followed by a 2 min infusion of St Thomas's Hospital cardioplegic solution with or without added diltiazem. All hearts were then subjected to global ischaemia (37 degrees C). The durations of ischaemia were 60 min in the neonatal and 45 min in the adult heart. Hearts were then reperfused (15 min Langendorff, 20 min working) before reassessment of function. 30 neonatal (7-10 d) and 30 adult (2-3 months) New Zealand white rabbits were used. The IC20 and IC50 of diltiazem were found to be 0.1 and 0.5 mumol.litre-1, respectively, in the neonatal heart, and 0.5 and 2.5 mumol.litre-1, respectively, in the adult heart. Postischaemic recovery of cardiac output was 57.9(SEM 6.7)% in the control group and 64.1(5.0)% (NS) and 47.7(3.8)% (NS) in the 0.5 mumol.litre-1 and 2.5 mumol.litre-1 diltiazem groups, respectively, in the adult hearts. In the neonatal hearts, cardiac output recovered to 55.6(4.8)% in the control group and 59.9(4.2)% (NS) and 62.0(5.6)% (NS) in the 0.1 mumol.litre-1 and 0.5 mumol.litre-1 diltiazem groups, respectively. The addition of diltiazem, at IC20 or IC50 negative inotropic concentrations, to St Thomas's Hospital cardioplegic solution does not improve postischaemic recovery in either neonatal or adult rabbit hearts. This suggests that the slow calcium channel may not be an important mediator of ischaemia and reperfusion induced injury in the cardioplegically arrested rabbit heart.