Acute haemodynamic effects of diltiazem and its distribution in relation to the myocardial infarction size

The aim of this study was to contribute to an elucidation of some possible mechanisms underlying harmful haemodynamic effects of calcium antagonist diltiazem in large myocardial infarctions in rats. Acute haemodynamic effects of i.v. diltiazem in a single dose of 0.5 mg/kg and the distribution of diltiazem in selected tissues was measured four weeks after surgical imposition of myocardial infarction in urethane (1.2 g/kg i.p.) anaesthetized rats. Hypotensive effect of diltiazem was significantly (r = 0.624) attenuated with an increasing infarction size. A significant relationship (r = -0.697) between change in stroke index and infarction size was observed. In rats with small infarctions (< 32% of the left ventricle circumference) there was an absolute increase, and in rats with large infarctions (> 32%) there was an absolute decrease in the stroke index. From the results obtained it seems likely that dilatation of ventricles without appropriate hypertrophy accompanying large infarctions is one of the main determinants of manifestation of negative inotropic potential of diltiazem.