Determinants of Acute Hemodynamic and Electrophysiologic Effects of Verapamil in Humans: Role of Myocardial Drug Uptake

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Abstract
To examine the relationship between myocardial verapamil content (MVC) and acute effects in humans, coronary sinus catheterization was used in 22 patients to determine myocardial uptake of verapamil after bolus intravenous (i.v.) verapamil (4 mg) injection. Verapamil-induced effects on hemodynamic and electrophysiologic parameters were measured simultaneously and correlated with MVC per unit baseline coronary sinus blood flow (MVC:F). Myocardial uptake of verapamil was rapid: peak MVC (1.2 ± 0.2% of injected dose) occurred at 5.4 ± 0.4 min; at 30 min, residual MVC was 71.1 ± 3.4% of maximum. Peak MVC:F in individual patients was inversely related to the extent of coronary artery disease (p < 0.005) but not to left ventricular (LV) systolic function. Verapamil produced significant (p < 0.001) early reductions in arterial pressure and systemic vascular resistance (SVR); cardiac index (CI) increased, left ventricular (LV) positive dP/dt was unchanged. Verapamil prolonged (p < 0.01) PR and AH intervals (maximum at 12–18 min) and atrioventricular (AV) nodal effective and functional refractory periods (ERP, FRP) (maximum at 30 min). In individual patients, the extent of changes in AH intervals (r = 0.69; p < 0.05) and LV dP/dt(r = 0.62; p < 0.05) correlated with peak MVC:F. We conclude that after i.v. injection, verapamil uptake by the human myocardium is rapid and more extensive in patients with minor coronary artery disease. Despite the hysteresis between MVC and drug effects, MVC is a determinant of inotropic and electrophysiologic effects of verapamil.