HEMODYNAMIC DOSE-RESPONSE EFFECTS OF IV VERAPAMIL IN CORONARY-ARTERY DISEASE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 9  (6) , 353-361
Abstract
As an aid to clinical therapeutic decisions, the hemodynamic dose-response effects following i.v. verapamil were evaluated in 10 male patients with angiographically confirmed and stable coronary artery disease. Sitting at rest, following a control period with 4 i.v. boluses of saline, 4 equivalent boluses of verapamil (logarithmic cumulative dosage; 2, 4, 8 and 16 mg) were administered at 4 min intervals; hemodynamic variable were recorded 2-4 min following each i.v. injection. The hemodynamic effects of the drug during upright bicycle exercise were evaluated by comparison of measurements made during a control steady-state exercise period with observations made at the same upright exercise workload (25-75 W) immediately following the maximum cumulative dose (16 mg). Following the 4 i.v. boluses, the plasma verapamil concentrations showed a log-linear increase (r = 0.82; P < 0.001); the levels achieved (26 .+-. 2 to 147 .+-. 14 .mu.g/l) were within the range at which substantial pharmacodynamic activity was shown to be present. At rest, compared with control measurements after saline, these plasma concentrations of verapamil were associated with linear decreases in systemic vascular resistance (maximum .DELTA.SVR-720 dyn .cntdot. s .cntdot. cm-5/ m2; P < 0.01) and blood pressure (maximum .DELTA.MBP-8 mmHg; P < 0.05) and linear increase in cardiac index (maximum .DELTA.CI + 0.41/min per m2 P < 0.05) and in pulmonary artery occluded pressure (maximum .DELTA.PAOP + 3 mm Hg; P < 0.05). There was no significant trend of change in the heart rate. During upright bicycle exercise, verapamil induced significant changes in left ventriculrr afterload and preload. Although the systemic arterial pressure was significantly less during exercise after the drug, the left heart filling pressure was signifcantly increased. There were no significant differences in exercise heart rate or cardiac output compared to control. At rest, the increase in cardiac output induced by verapamil probably indicates the favorable influence of its systemic arteriolar dilator activity on the pressure-work load of the ischemic left ventricle, the improved cardiac performance was not associated with appreciable effects on left heart filling pressure until the final 16 mg cumulative dosage. During the stress of dynamic exercise, the negative inotropic effects of verapamil appear to predominate; despite the reduced systemic blood pressure, there was a significant increase in left heart filling pressure at the same cardiac output and heart rate. Verapamil (2 to 8 mg) evidently is hemodynamically well-tolerated even in relatively severe coronary heart disease; higher dosage (16 mg) is accompanied by clear-cut and potentially detrimental depression of cardiac performance.