To evaluate the effects of vasodilator therapy, the quantitative relationships between peripheral resistance, LVEDP, coronary circulation and cardiac output were analyzed by using 23 isolated coronary perfused canine heart which afterload, preload, coronary blood flow and heart rate are able to regulate independently. Peripheral resistance was decreased incrementally to lower mean arterial pressure from 107-97 mmHg to 48-22 mmHg keeping preload and heart rate at constant level. A decrease in mean arterial blood pressure to 72 ( physiologically coronary perfused heart) and 68 mmHg (coronary stenosed model) increased cardiac output, respectively. However, myocardial oxygen consumption in each group decreased under 5.5 ml/min/100g LV which suggested myocardial ischemia worsen and further decrease in blood pressure lowered cardiac output. LVEDP also decreased incrementally from 18-20 mmHg to 5 mmHg keeping afterload at 100 mmHg of mean arterial blood pressure constantly. A decrease in LVEDP from 20 to 14 mmHg reduced stroke work index in normal heart but increased slightly in failing heart. Further lowering in LVEDP resulted decreasing in stroke work index in both group. Thus modest and adequate reduction in preload and afterload has beneficial effects to cardiac function. In contrast, further decrease will worsen myocardial perfusion and cardiac function.