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) contractile performance and diastolic filling dynamics in eight conscious animals. After administering metoprolol and atropine, felodipine (25 nmol/kg i.v.) produced significant decreases in LV end-systolic pressure (PES) (109 +/- 15 vs. 88 +/- 12 mmHg, P < .05) and arterial elastance (Ea) (12.6 +/- 4.5 vs. 8.5 +/- 3.4 mmHg/ml, P < .05), whereas the heart rate was unchanged. Felodipine increased the slopes of the end-systolic P-V relation (7.4 +/- 0.9 vs. 9.9 +/- 1.0 mmHg/ml, P < .05), the dP/dtmax-end diastolic volume (VED) relation (68.1 +/- 11.2 vs. 94.9 +/- 14.3 mmHg/sec/ml, P < .05), and the stroke work (SW)-VED relation (72.1 +/- 3.1 vs. 82.8 +/- 5.2 mmHg, P < .05), and shifted all three relations to the left, indicating enhanced contractile performance. In contrast, at doses that produced equivalent reductions of PES, nifedipine (375 nmol/kg i.v.) and amlodipine (780 nmol/kg i.v.), significantly decreased the slopes of the end-systolic P-V relation, the dP/dtmax-VED relation and the SW-VED relation and shifted all three relations to the right, indicating depressed LV contractile performance. 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 rate of early diastolic LV filling (dV/dtmax) (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/dtmax (173 +/- 39 to 154 +/- 30 ml/sec, P < .05), whereas nifedipine had no significant effects on T, PGmax or dV/dtmax. Thus, we conclude that in conscious dogs after autonomic blockade, at dosages that produced equivalent arterial vasodilation, felodipine augmented, whereas amlodipine depressed, LV contractile performance, LV relaxation and early LV filling. Nifedipine decreased LV contractile performance but had no significant effect on LV relaxation and early LV filling.
Cheng
C P
CP
Section of Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
Noda
T
T
Nordlander
M
M
Ohno
M
M
Little
W C
WC
D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D015736:Felodipine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine; D015736:Felodipine