Frequency-dependent myocardial depression induced by verapamil in conscious dogs

To determine the effects of calcium entry-blocking drugs on the frequency-dependent rate of peak positive left ventricular pressure development [(+)dP/dtmax] we evaluated the effects of incremental left atrial pacing during verapamil, diltiazem, and nifedipine under equivalent loading conditions in seven conscious preinstrumented mongrel dogs. To eliminate the effects of reflex sympathetic stimulation the animals were pretreated with propranolol (2 mg/kg). Prior to atrial pacing (+)dP/dtmax was similar for verapamil [2,392 +/- 416 (SD) mmHg/s], diltiazem (2,661 +/- 606 mmHg/s), and nifedipine (2,731 +/- 636 mmHg/s), P = NS among drugs. At a common peak paced heart rate (150 beats/min) under equivalent loading conditions, (+)dP/dtmax was significantly reduced from the corresponding preatrial pacing value only after verapamil (2,131 +/- 415 mmHg/s, P less than 0.03) and was significantly lower than after either diltiazem (2,547 +/- 550 mmHg/s) or nifedipine (2,633 +/- 705 mmHg/s, P less than 0.04). No significant linear relation was observed between stimulation frequency and (+)dP/dtmax during atrial pacing alone (slope = -2.2 +/- 1.3, r = -0.30 +/- 0.23, P = 0.12), during atrial pacing with beta-blockade alone (slope = 1.7 +/- 1.5, r = 0.24 +/- 0.25, P = 0.25), or beta-blockade combined with diltiazem (slope = -0.91 +/- 1.3, r = 0.02 +/- 0.23, P = 0.38) or nifedipine (slope = -1.2 +/- 1.3, r = 0.01 +/- 0.23, P = 0.48). By contrast, a significant negative force-frequency relation was seen during incremental atrial pacing after verapamil (slope = -4.1 +/- 1.3, r = -0.80 +/- 0.23, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)