Effects of diltiazem on regional coronary hemodynamics during atrial pacing in patients with stable exertional angina: implications for mechanism of action.

Abstract

To investigate the mechanism of the antianginal action of diltiazem in stress-induced myocardial ischemia, we studied 12 patients with stable exertional angina and disease of the proximal left anterior descending artery by measuring great cardiac vein flow (GVCF) and calculating anterior regional coronary resistance (ARCR) during myocardial ischemia induced by atrial pacing before and after intravenous administration of diltiazem (0.25 mg/kg in a bolus dose followed by continuous infusion of 0.005 mg/kg/min). Diltiazem increased the pacing time to angina from 6.9 ± 3.5 to 10.7 + 4 min (p < .001). At peak pacing heart rate was increased after diltiazem ( Circulation 73, No. 6, 1248-1253, 1986 DILTIAZEM is a calcium channel-blocking agent that has been shown to improve exercise tolerance in patients with exertional angina.'-' It is not known, however, whether the beneficial effects of the drug are achieved by a decrease in myocardial oxygen demand at any level of exertional stress or if they are a result of an increase in coronary flow.9 In this study we evaluated the effects of diltiazem on coronary hemodynamics in a selected group of patients with stable exerciseinduced angina and disease of the proximal left anterior descending artery. Thermodilution measurements of great cardiac vein flow (GCVF), representing the venous efflux from the territory supplied by the left anterior descending artery,"'-'2 were obtained at rest and during ischemia induced by atrial pacing performed before and after intravenous administration of diltiazem. The effects of the drug on anginal threshold were then related to coronary hemodynamics and changes in oxygen consumption of the myocardial region in which perfusion was jeopardized. MethodsStudy patients. The study group consisted of 12 patients (1 1 men and one woman, mean age 55 + 7 years) with stable exertional angina and a positive exercise test result, defined as the development of chest pain and 1 mm or more ST segment depression in the precordial leads. Patients whose angina predominantly occurred at rest or who showed ST segment elevation suggestive of variant angina were not included in this study. No patient had clinical evidence of heart failure or had had a myocardial infarction within 6 months of the study. In no patient were pathologic Q waves observed in the precordial leads. The patients underwent coronary arteriography, which revealed significant coronary artery disease (> 50% diameter narrowing of one or more vessels) that in all cases involved the proximal portion of the left anterior descending artery. No patient had left main coronary artery disease.Procedure. All patients were studied while in the fasting state 1 to 10 days after coronary arteriography and none received premedication. Nitrates and nifedipine were suspended 12 hr before the study; four patients who were taking ,8-blockers were gradually weaned and the drug was discontinued at least 1 CIRCULATION by guest on May 9, 2018 http://circ.ahajournals.org/ Downloaded from

Diltiazem

“…Intravenous diltiazem in total doses of 0.3 to 0.8 mg/kg reduced mean arterial pressure and systemic vascular resistance during peak exercise (Legrand et al 1984;Silke et al 1987) or atrial pacing (De Servi et al 1986;Remme et al 1987;Serruys et al 1985); heart rate was either decreased or remained constant.…”