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 Ca(2+) 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.


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 Ca(2+) channel blockade with amlodipine (1.5 mg/kg/day) and rapid pacing (n = 7), 3) concomitant Ca(2+) 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 microm/s v 87 +/- 9 microm/s, P <.05), and increased from pacing CHF values with amlodipine or nifedipine treatment (62 +/- 8 microm/s, 64 +/- 4 microm/s, respectively; P <.05). Inotropic response to extracellular Ca(2+) (8 mmol/L) was reduced with pacing CHF (94 +/- 5 microm/s v 160 +/- 15 microm/s, P <.05) and increased from CHF values with amlodipine or nifedipine treatment (132 +/- 14 microm/s and 133 +/- 7 microm/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 Ca(2+) channel blockade.
McElmurray
J H
JH
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Mukherjee
R
R
Patterson
T M
TM
Goldberg
A
A
King
M K
MK
Hendrick
J W
JW
Gay
D M
DM
Clair
M J
MJ
Jolly
J R
JR
Spinale
F G
FG
D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D018715:Microscopy, Video; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology* / Q000627:therapeutic use*; D010138:Pacemaker, Artificial; D013552:Swine; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine