Cardiovascular effects of diltiazem in the dog

The effects of two bolus injections (0.2 mg kg-1) and two infusion rates (0.2 mg min-1 and 0.4 mg min-1) of diltiazem on global and regional left (LV) and right ventricular (RV) performance (ultrasonic dimension technique), on coronary (electromagnetic flow meters) and systemic haemodynamics, and on electrophysiology (PR, QRS, QTc intervals) were studied in eight open-chest dogs anaesthetized with droperidol and fentanyl. The two bolus injections of diltiazem resulted in plasma concentrations of 688 +/- 115 and 650 +/- 85 ng ml-1 (means +/- SE), respectively, and caused substantial decreases in systemic and coronary vascular resistances, and in aortic pressure, and increases in LV segment shortening, stroke volume and aortic flow. Electrophysiological variables were little affected. At the low infusion rate (plasma concentration 140 +/- 23 ng ml-1) coronary and systemic vasodilatation occurred, but global and regional RV and LV performance were little affected. PR interval increased by 15%. At the higher infusion rate (plasma concentration 282 +/- 33 ng ml-1) coronary and systemic vasodilatation were maintained. Aortic pressure decreased slightly. Whereas LV end-diastolic and end-systolic dimensions remained unchanged, they increased in the RV. In addition, the PR interval increased by 35%, and three animals developed atrioventricular block type I. The data indicate that diltiazem is a potent coronary and systemic vasodilator with little effect on global RV and LV performance. However, at a higher infusion rate RV dimensions clearly tend to increase, and conduction abnormalities develop.