Differential effects of systemic and intracoronary calcium channel blocking agents on global and regional left ventricular function in conscious dogs

Abstract

We examined the differential effects of intravenous (IV) equimolar doses of diltiazem (D), verapamil (V), and nifedipine (N) upon left ventricular (LV) function in 12 healthy unsedated dogs. We also attempted to isolate direct myocardial effects of these agents from reflex and peripheral effects by using intracoronary (IC) equimolar drug administration in an additional six animals. Despite equivalent dose-related increases in heart rate and declines in arterial pressure intravenous V (0.04, 0.1, 0.17 mg/kg) and N (0.3 mg/kg) but not D (0.04, 0.1, 0.17 mg/kg) depressed LV function. Peak effects after high dose V included increased heart rate (HR) (68%) and reduced mean aortic pressure (MAP) (17%), dP/dt max (22%), and percent shortening of the LV minor diameter (% delta D) (33%) (all p less than or equal to 0.001). By contrast, equimolar D increased HR (68%) and decreased MAP (20%) but produced no change in dP/dt or % delta D while low dose N (0.03 mg/kg) depressed dP/dt and % delta D by 37% and 45%, respectively (both p less than or equal to 0.001) despite similar changes in HR and MAP. Pretreatment with propranolol (2 mg/kg) and matching HR and loading conditions to control failed to uncover myocardial depression after D. Equimolar IC D, V (4, 8, 16 micrograms/kg), or N (3 micrograms/kg) each produced dose-related reductions in percent regional shortening which were greatest with N (58% at 3 micrograms/kg) and least with D (9% at 16 micrograms/kg). These data suggest that calcium channel blockers vary in their propensity to reduce LV function and that the myocardial depressant effects of these agents are partially offset by reflex and peripheral vascular actions.