Nisoldipine improves ventricular function in rats with ischemic heart failure

To determine whether calcium channel blockade is effective in the prevention of the cascade of events leading to the thin walled, decompensated ventricle observed in ischemic heart failure, inhibition of transsarcolemmal transport of calcium by nisoldipine was examined in rats in which luminal narrowing of the left main coronary artery was utilized to produce global cardiac ischemia. Coronary artery narrowing was produced in rats at 2 months of age and animals were maintained on nisoldipine (10 mg/kg body weight) (CANN) or water (CANW) until time of sacrifice 1 month later. Surgical intervention resulted in a 50% reduction in coronary artery luminal diameter in both experimental groups and was associated with an increase in kidney and lung weights in only CANW animals. Heart weights were also increased in the water treated coronary artery narrowed group. In CANW rats, systemic arterial and left ventricular systolic pressures were reduced whereas left ventricular diastolic pressures were elevated. Peak rates of pressure rise and decay and cardiac output were also reduced in CANW rats. Treatment with nisoldipine prevented the detrimental impact of ischemic heart disease to an extent that all measured parameters in CANN rats were found to be intermediate between unoperated controls and CANW animals. Thus, calcium channel blockade was therapeutic in the prevention of cardiac dysfunction and failure seen after the onset of ischemic heart disease in rats. Furthermore, the detrimental impact of ischemic heart disease was ameliorated by early and continuous treatment with the calcium channel blocker, nisoldipine.