Haemodynamic dose-response effects of i.v. verapamil in coronary artery disease

Abstract

As an aid to clinical therapeutic decisions, the haemodynamic dose-response effects following intravenous verapamil were evaluated in ten male patients with angiographically confirmed and stable coronary artery disease. Sitting at rest, following a control period with four i.v. boluses of saline, four equivalent boluses of verapamil (logarithmic cumulative dosage; 2, 4, 8 and 16 mg) were administered at four minute intervals; haemodynamic variables were recorded two to four minutes following each i.v. injection. The haemodynamic 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 to 75 W) immediately following the maximum cumulative dose (16 mg). Following the four i.v. boluses, the plasma verapamil concentrations showed a log-linear increase (r = 0.82; p less than 0.001); the levels achieved (26 +/- 2 to 147 +/- 14 micrograms/l) were within the range at which substantial pharmacodynamic activity has been 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 dyne X s X cm-5/m2; p less than 0.01) and blood pressure (maximum delta MBP -8 mmHg; p less than 0.05) and linear increases in cardiac index (maximum delta CI +0.4 l/min/m2; p less than 0.05) and in pulmonary artery occluded pressure (maximum delta PAOP +3 mmHg; p less than 0.05). There was no significant trend of change in the heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)