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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 less than .001). At peak pacing heart rate was increased after diltiazem (from 128 +/- 17 to 145 +/- 17 beats/min, p less than .005), while mean arterial pressure was decreased (from 131 +/- 19 to 113 +/- 17 mm Hg, p less than .025), leaving the double product unaltered. At peak pacing no changes were observed in GCVF (from 115 +/- 46 to 119 +/- 46 ml/min, p = NS), ARCR (from 1.3 +/- 0.4 to 1.1 +/- 0.4 mm Hg/ml/min), or myocardial oxygen consumption of the anterior region (from 14.5 +/- 4.2 to 13.4 +/- 4.7 ml/min). Reduction of myocardial oxygen demand plays a major role in the antianginal action of diltiazem in patients with stress-induced myocardial ischemia.

The effects of short term intravenous administration of gallopamil on coronary haemodynamic variables were studied in 10 patients with stable exertional angina and angiographically confirmed coronary artery disease that affected the proximal portion of the left anterior descending artery. Blood flow in the great cardiac vein was measured by a thermodilution technique, both at rest and during ischaemia induced by atrial pacing, before and after intravenous administration of gallopamil (0.02 mg/kg as a bolus dose given over three minutes, followed by an infusion of 0.0005 mg/kg/min). Gallopamil significantly prolonged the mean (SD) duration of pacing that was tolerated (11 (2.6) vs 14.8 (2.4] min, significantly increased the mean (SD) peak heart rate attained during pacing (142 (15) vs 158 (11) beats/min), and reduced mean (SD) arterial pressure (133 (17) vs 116 (17) mm Hg). There were no changes in mean (SD) blood flow in the great cardiac vein (134.1 (57) vs 112.9 (38) ml/min, mean (SD) anterior regional coronary resistance (1.18 (0.6) vs 1.15 (0.5) mm Hg/ml/min), and mean (SD) anterior regional myocardial oxygen consumption (16.6 (6) vs 13.7 (4) ml/min). These data confirm that gallopamil is an effective antianginal agent and suggest that a reduction of myocardial oxygen demand is the predominant mechanism by which the drug exerts its beneficial effects.

To verify whether beta-endorphin plasma levels influence the presence of anginal symptoms, 74 consecutive male patients were studied. All patients had previously documented coronary artery disease and reproducible exercise-induced myocardial ischemia. Thirty-five patients (Group I) had a history of angina and reported anginal symptoms during exercise stress testing; 39 patients (Group II) were asymptomatic and had documented silent myocardial ischemia during exercise. Baseline beta-endorphin plasma levels were measured in blood samples taken before exercise stress testing and analyzed by beta-endorphin-I125-RIA Kit-NEN (a radioimmunoassay method). The mean baseline beta-endorphin plasma level was 22.5 +/- 19 pg/ml in patients with anginal symptoms compared with 43.7 +/- 28 pg/ml in asymptomatic patients (p less than 0.001). Baseline blood pressure and heart rate-systolic pressure (rate-pressure) product at baseline and at ischemia threshold (1 mm ST segment depression) were similar in the two groups. Group II patients had a longer exercise duration (p less than 0.01), more pronounced ST segment depression (p less than 0.001) and a higher peak rate-pressure product (p less than 0.01). The extent of coronary artery disease, ejection fraction and left ventricular end-diastolic pressure were similar in the two groups. These data suggest that higher baseline beta-endorphin plasma levels may play a role in the decreased sensitivity to pain in patients with silent myocardial ischemia. In addition, different beta-endorphin levels can be associated with a different sensitivity to pain.