Effects of diltiazem on total cardiac output distribution in conscious rats

The present study was conducted to determine the effect of a "calcium channel blocker," diltiazem (DZ), on cardiovascular dynamics and the distribution of total cardiac output in the conscious rat. Animals were instrumented for right atrial, left ventricular, arterial and venous pressure recordings and the radioactive microsphere technique was used to measure regional blood flow and cardiac output before (control) and during the intravenous infusion of either DZ at three dosage levels (0.4, 2.0, and 10.0 mg/kg/hr) or saline placebo at rates matching those of the DZ protocol (0.015, 0.1 and 0.5 ml/min). Maximum volume infusion rate equaled approximately a 2% increase in blood volume/minute. Systemic vascular resistance, stroke volume, regional vascular resistances and the regional percent distribution of total cardiac output were calculated. In the experimental group (n = 9, body weight = 404 +/- 7 g), DZ, at the highest dose, caused a nonsignificant increase in cardiac output of 61% (cardiac output decreased in one animal) and a significant drop in systemic vascular resistance (45%) while no changes occurred in the control group (n = 5, body weight = 440 +/- 9 g). The major effect of DZ was to increase blood flow and reduce vascular resistance in the coronary circulation (percent distribution of total cardiac output to the coronary circulation, control vs. maximum infusion: saline placebo, 3.9 +/- 0.5 to 4.5 +/- 0.4%; DZ, 3.5 +/- 0.5 to 6.9 +/- 0.5%, P less than .01). The results indicate that DZ does not suppress cardiac function and may actually increase cardiac output secondary to afterload reduction. DZ results in a balanced increase in regional blood flow and no major change in total cardiac output distribution in the conscious rat.