Aggravation of left ventricular dilatation and reduction of survival by a calcium channel blocker in rats with chronic myocardial infarction

The mechanism of adverse effects of calcium channel blockade on cardiac performance and survival in patients with cardiac dysfunction after myocardial infarction is controversial. To test whether left ventricular dilatation and remodeling, as predictors of long-term survival and cardiac performance, are important, rats with healed infarcts received a vasodilating calcium channel blocker (anipamil) or placebo. After 8 weeks the mortality rate (total population n = 111) was 35% with calcium channel blockade and 4% with placebo in rats with infarction ( p < 0.001). In survivors with large infarctions (44% ± 12% of left ventricle, n = 9), calcium channel blockade did not aggravate left ventricular dysfunction and decreased chamber stiffness, but increased left ventricular volume (1.55 ± 0.13 ml/kg, p = 0.03 vs placebo: 1.16 ± 0.11 ml/kg; n = 11) (passive pressure-volume relationship) at persistently elevated volume/mass ratio. Thus this study shows for the first time that aggravation of left ventricular dilatation and remodeling is one important mechanism by which calcium channel blockade may reduce survival in the presence of ventricular dysfunction after myocardial infarction.