CARDIOPULMONARY EXERCISE TESTING IN THE E VALUATION OF CARDIOVASCULARDRUGS

In the evaluation of drugs intended to alleviate symptomatology and to improve exercise capacity in congestive heart failure, various pathop hysiologic mechanisms including impairment of cardiac output, oxygenat ion of blood, muscle blood flow, and muscle metabolism have to be cons idered. In Various forms of acute and chronic heart failure these mech anisms contribute more or less to impaired oxygen uptake. In acute for ms of heart failure pulmonary congestion and its effects on airway res istance and lung capacity might be the predominating mechanisms of sym ptoms, while in chronic heart failure impedement of muscle blood flow and metabolic changes, comparable with deconditioning, are additional pathomechanisms. The increase in cardiac output and in muscle blood fl ow provided by some positive inotropic agents and by vasodilators afte r acute administration is often paralleled by a decrease in arterioven ous oxygen difference and does not lead to an improvement of oxygen up take. However, chronic therapy with some vasodilators can lead to impr ovement in oxygen uptake, either due to training effects or due to flo w dependent or direct effects on muscle metabolism. In pulmonary conge stion a decrease of elevated filling pressures can acutely lead to som e improvement of exercise capacity. Furthermore, chronic decrease in f illing pressures by administration of diuretics, nitrates, ACE-inhibit ors or dopaminergic drugs leads to long-term improvement in oxygen upt ake. By comparing hemodynamic effects of acute and chronic drug therap y in CHF with their effects on exercise capacity, the chronic decrease of filling pressures seems to be the major hemodynamic variable leadi ng to improvement of exercise capacity. Even marked increases in cardi ac output, however, neither in acute nor in chronic therapy have consi stently lead to improvement of exercise capacity or oxygen uptake unle ss accompanied by a long lasting decrease in filling pressures at rest . Cardiopulmonary exercise testing (CPX) is useful in differentiating these various pathophysiological mechanisms and is thus extremely usef ul in patients with a variety of cardiovascular problems and their pha rmaceutical management. It has become a mandatory prerequisite in all heart failure trials.