Comparison of amlodipine or nifedipine treatment with developing congestive heart failure: Effects on myocyte contractility

Abstract

Background: Past studies have suggested that amlodipine, a dihydropyridine L-type Ca2+ channel antagonist, may exert useful effects in congestive heart failure (CHF). The present study examined the effects of amlodipine or nifedipine treatment in a model of developing CHF on left ventricular (LV) pump function and myocyte contractility. Methods and Results: Pigs (25 kg) were randomly assigned to 1 of 4 groups: 1) pacing-induced CHF (rapid atrial pacing at 240 bpm) for 3 weeks (n = 9), 2) concomitant Ca2+ channel blockade with amlodipine (1.5 mg/kg/day) and rapid pacing (n = 7), 3) concomitant Ca2+ channel blockade with nifedipine (0.7 mg/kg twice daily) and rapid pacing (n = 7), and 4) sham controls (n = 7). LV fractional shortening fell with pacing CHF from baseline values (17% ± 1% v 42% ± 1%, P <.05). With rapid pacing and concomitant amlodipine treatment, LV fractional shortening increased from pacing CHF values (24% ± 1%, P <.05) but was unchanged with concomitant nifedipine treatment (20% ± 2%, P =.2). LV myocyte velocity of shortening, as measured by high speed videomicroscopy, was reduced with pacing CHF compared with controls (42 ± 2 μm/s v 87 ± 9 μm/s, P <.05), and increased from pacing CHF values with amlodipine or nifedipine treatment (62 ± 8 μm/s, 64 ± 4 μm/s, respectively; P <.05). Inotropic response to extracellular Ca2+ (8 mmol/L) was reduced with pacing CHF (94 ± 5 μm/s v 160 ± 15 μm/s, P <.05) and increased from CHF values with amlodipine or nifedipine treatment (132 ± 14 μm/s and 133 ± 7 μm/s, respectively, P <.05) Conclusions: These results suggest that the primary mechanism for the effects of amlodipine on myocyte contractility in developing CHF is because of direct Ca2+ channel blockade.