Biochemical and physiologic response to isoproterenol in patients with left ventricular failure

Isoproterenol, the prototype beta-adrenergic agonist, reverses the physiologic defects of the failing left ventricle toward normal: decreased ventricular end-diastolic volume and pressure, increased ejection fraction, rate of rise of ventricular pressure and mean systolic ejection rate. There is also an increase in mean velocity of fiber shortening and in calculated maximal velocity of shortening of contractile elements. These responses of the heart are integrated with increase in heart rate and venous return to augment cardiac output to the periphery. The enhanced contractile state and work output of the heart produced by isoproterenol are associated with increases in coronary vasodilatation and coronary blood flow, with decrease in coronary arteriovenous oxygen differences. Myocardial oxygen consumption usually increases commensurate to demand, although in ischemic heart disease isoproterenol may induce myocardial lactate production as an anaerobic source of energy. Increases in energy requirement due to the enhanced contractile state may be offset in part by the reduction in ventricular wall stress associated with decreased ventricular volume. These effects of isoproterenol on cardiac muscle are accompanied by activation of adenyl cyclase, a membrane receptor that leads to increases in intracellular cyclic 3′5′ adenosine monophosphate, the "messenger" hormone that activates phosphorylase and glycogenolysis. The specific intracellular mechanism whereby isoproterenol increases myocardial contractility is not yet clear.