Verapamil in chronic stable angina: Amelioration of pacing-induced abnormalities of left ventricular ejection fraction, regional wall motion, lactate metabolism and hemodynamics

Abstract

The effects of intravenously administered verapamil (bolus dose of 0.145 mg/kg body weight, followed by continuous infusion at 0.005 mg/kg per min) on myocardial ischemia induced by incremental coronary sinus pacing were investigated in 12 patients with coronary artery disease undergoing diagnostic angiography. The effects were determined with respect to differences between changes under control pacing conditions and after verapamil in the transmyocardial gradients of lactate, systemic hemodynamics and in left ventricular ejection fraction and regional wall motion abnormalities measured with gated radionuclide ventriculography. Control and drug data could not be matched for four patients because of the development of atrioventricular (A-V) Wenckebach block at lower pacing rates during verapamil infusion. In the remaining eight patients, under control conditions, pacing to a mean maximal heart rate of 120.6 ± 10.8 beats/min produced moderate to severe chest pain in all; the left ventricular ejection fraction decreased from 0.59 ± 0.08 to 0.47 ± 0.07 (−20.2 percent, p < 0.001) with the development of new regional wall motion abnormalities in seven patients and an accentuation of the preexisting abnormality in the remainder. During verapamil administration, the left ventricular ejection fraction decreased from 0.55 ± 0.07 to 0.52 ± 0.04 (−5.5 percent, difference not significant); no regional wall motion abnormalities developed. Four patients had no chest pain; in the other four, the pain at maximal pacing was minimal or mild in intensity. Under control conditions, the maximal pacing rate led to a decrease in myocardial lactate extraction in all patients, with metabolism becoming anaerobic in four. During administration of verapamil, identical pacing rates produced no abnormalities of the transmyocardial lactate gradient while preventing the increases in pulmonary capillary wedge pressure and in pulmonary and systemic arterial pressures observed under control conditions. The overall data, demonstrating that verapamil, when given under steady state conditions of drug administration, prevents or greatly attenuates the ischemic consequences of incremental coronary sinus pacing in patients with coronary artery disease, provide objective evidence for the clinical utility of the compound in exertional angina. Controlled clinical trials during oral therapy with the drug are therefore indicated.