COMPARISON OF EFFECTS OF DIHYDROPYRIDINE CALCIUM-ANTAGONISTS ON LEFT-VENTRICULAR SYSTOLIC AND DIASTOLIC PERFORMANCE

We compared the effects of three dihydropyridine calcium antagonists ( felodipine, nifedipine and amlodipine) on left ventricular (LV) contra ctile performance and diastolic filling dynamics in eight conscious an imals. After administering metoprolol and atropine, felodipine (25 nmo l/kg i.v.) produced significant decreases in LV end-systolic pressure (PES) (109 +/- 15 vs. 88 +/- 12 mmHg, P < .05) and arterial elastance (E(a)) (12.6 +/- 4.5 vs. 8.5 +/- 3.4 mmHg/ml, P < .05), whereas the he art rate was unchanged. Felodipine increased the slopes of the end-sys tolic P - V relation (7.4 +/- 0.9 vs. 9.9 +/- 1.0 mmHg/ml, P < .05), t he dP/dt(max)-end diastolic volume (V-ED) relation (68.1 +/- 11.2 vs. 94.9 +/- 14.3 mmHg/sec/ml, P < .05), and the stroke work (SW)-V-ED rel ation (72.1 +/- 3.1 vs. 82.8 +/- 5.2 mmHg, P <.05), and shifted all th ree relations to the left, indicating enhanced contractile performance . In contrast, at doses that produced equivalent reductions of P-ES, n ifedipine (375 nmol/kg i.v.) and amlodipine (780 nmol/kg i.v.), signif icantly decreased the slopes of the end-systolic P-V relation, the dP/ dt(max) - V-ED relation and the SW - V-ED relation and shifted all thr ee relations to the right, indicating depressed LV contractile perform ance. Felodipine decreased the time constant (T) of LV relaxation (32. 2 +/- 5.2 to 28.8 +/- 5.2 msec, P < .05) and increased the maximum rat e of early diastolic LV filling (dV/dt(max)) (167 +/- 22 to 207 +/- 26 ml/sec, P < .05). Amlodipine had the opposite effect, slowing T (31.0 +/- 4.9 to 33.9 +/- 5.4 msec, P < .05) and decreasing dV/dt(max) (173 +/- 39 to 154 +/- 30 ml/sec, P < .05), whereas nifedipine had no sign ificant effects on T, PG(max) or dV/dt(max). Thus, we conclude that in conscious dogs after autonomic blockade, at dosages that produced equ ivalent arterial vasodilation, felodipine augmented, whereas amlodipin e depressed, LV contractile performance, LV relaxation and early LV fi lling. Nifedipine decreased LV contractile performance but had no sign ificant effect on LV relaxation and early LV filling.