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

Background: Past studies have suggested that amlodipine, a dihydropyridine L-type Ca2+ channel antagonist, may exert useful effects in congestive hear t failure (CHF). The present study examined the effects of amlodipine or ni fedipine treatment in a model of developing CHF on left ventricular (LV) pu mp 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 r apid 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 (2 0% +/- 2%, P = .2). LV myocyte velocity of shortening, as measured by high speed videomicroscopy, was reduced with pacing CHF compared with controls ( 42 +/- 2 mum/s v 87 +/- 9 mum/s. P < .05), and increased from pacing CHF va lues with amlodipine or nifedipine treatment (62 +/- 8 <mu>m/s, 64 +/- 4 mu m/s. respectively; P < .05). Inotropic response to extracellular Ca2+ (8 mm ol/L) was reduced with pacing CHF (94 +/- 5 v 160 +/- 15 <mu>m/s, P < .05) and increased from CHF values with amlodipine or nifedipine treatment (132 +/- 14 <mu>m/s and 133 +/- 7 mum/s, respectively, P < .05) Conclusions: These results suggest that the primary mechanism for the effec ts of amlodipine on myocyte contractility in developing CHF is because of d irect Ca2+ channel blockade.