EFFECTS OF FELODIPINE ON LEFT-VENTRICULAR SYSTOLIC AND DIASTOLIC PERFORMANCE IN CONGESTIVE-HEART-FAILURE

We studied the effects of a dihydropyridine calcium blocker, felodipin e, on left ventricular (LV) contractile performance and diastolic fill ing dynamics in conscious dogs with pacing-induced congestive heart fa ilure (CHF) before and after autonomic blockade. Eleven conscious dogs were instrumented to measure micromanometer LV and left atrial (LA) p ressure (P) and to determine LV volume (V) from three dimensions. CHF was induced by 4 to 5 weeks of right ventricular pacing. After CHF, th e mean LV end-diastolic (ED) P increased (9.7 +/- 2.9 vs. 27.9 +/- 6.8 mm Hg, P < .05), LVEDV and end-systolic (ES)V increased and stroke vo lume (SV) decreased (15.3 +/- 2.4 vs. 9.6 +/- 3.0 ml, P < .05). The ti me constant of LV relaxation (T) (25.9 +/- 2.9 vs. 37.9 +/- 5.1 msec, P < .05) and LVES wall stress (WS) (63.4 +/- 21.0 vs. 74.6 +/- 23.7 g/ cm(2), P < .05) also increased. After CHF, felodipine (25 nmol/kg i.v. , plasma concentrations 17.4 +/- 3.2 nmol/L) produced significant decr eases in LVESP (119 +/- 12 vs. 96 +/- 11 mm Hg, P < .05), arterial ela stance, total systolic resistance (TSR) (0.11 +/- 0.04 vs. 0.07 +/- 0. 03 mm Hg/ml/min, P < .05) and LVESWS (74.6 +/- 23.7 vs. 60.2 +/- 17.3 g/cm(2), P < .05). Felodipine increased the slopes of the ESP-V relati on (5.6 +/- 1.5 vs. 7.8 +/- 0.7 mm Hg/ml, P < .05), the dP/dt(max)-EDV relation (51.4 +/- 6.1 vs. 85.3 +/- 10.1 mm Hg/ml sec, P < .05) and t he stroke work-EDV relation (69.8 +/- 7.1 vs. 78.9 +/- 7.1 mm Hg, P < .05) and shifted all three relations to the left, indicating enhanced contractile performance. After CHF, felodipine decreased T (37.9 +/- 5 .1 vs. 31.4 +/- 6.2 msec, P < .05) and increased maximum mitral valve P gradient (PG(max) (4.9 +/- 1.8 vs. 6.7 +/- 3.3 mm Hg) and maximum ra te of early diastolic LV filling (dV/dt(max) (183 +/- 69 vs. 209 +/- 8 4 ml/sec, P < .05). Mean LAP (22.7 +/- 6.5 vs. 19.1 +/- 6.0 mm Hg, P < .05) and minimum LVP (18.3 +/- 2.9 vs. 12.7 +/- 4.8 mm Hg, P < .05) d ecreased. Similar results were obtained in a subgroup of four animals after autonomic blockade. In conscious dogs with CHF, felodipine produ ces arterial vasodilation, enhances LV relaxation and the rate of LV e arly filling and increases LV contractile performance.