The direct effects of CP on the heart muscle were studied in anesthetized open-chest dogs by intracoronary infusion of chlorpromazine (CP) to LAD in doses of 0.01 and 0.1 mg at the flow ste of 1 ml/min. At 0.01 mg/ml/min of CP, no significant changes in the measurements were observed. At 0.1 mg/ml/min, CP caused a gradual increase in heart rate and CBF of LAD without changes in systemic blood pressure and cardiac output. In the LAD area, systolic expansion of the heart muscle (systolic bulge) occurred in 6 out of 14 dogs (43%). In 8 dogs having no bulge, systolic shortening of segmental myocardium of the infused area decreased by 9.4% and end-systolic length increased, while in the control (LCX) area, systolic shortening of the heart muscle increased markedly with a reduction in the end-diastolic length. Local QTc was prolonged in the LAD area, but did not change in the LCX area. In the LAD area, more prolongation of QTc was observed in the dogs with bulge than the dogs without bulge. Pretreatment with CoQ(10) completely prevented CP-induced bulge. No significant changes in other measurements including QTc were observed in comparison with dogs without CoQ(10) pretreatment. These results suggest that the effects of CP are of direct myocardial suppression and are incompletely preoented by CoQ(10) pretreatment.
direct effect of heart muscle