The aerobic exercise capacity of patients with chronic stable heart failure is frequently reduced. It has been postulated that this exercise intolerance is due to inadequate perfusion of working skeletal muscle. The objectives of the present study are: 1) to determine if skeletal muscle perfusion is attenuated during dynamic bicycle exercise in patients with heart failure; 2) to investigate the mechanisms responsible for altered perfusion patterns; and 3) to determine if pharmacological vasodilators can be used to improve skeletal muscle oxygen availability during exercise. Skeletal muscle perfusion during exercise will be estimated by measuring femoral venous blood flow during upright bicycle exercise using a thermodilution catheter. The adequacy of oxygen delivery to skeletal muscle will be determined by sampling femoral venous effluent and calculating leg oxygen uptake and lactate production. Perfusion abnormalities in heart failure will be characterized by comparing flow and metabolic response to exercise in patients with and without heart failure. The relative contributions of diminished cardiac pump function versus increased vasoconstrictor activity to altered flow regulation will be evaluated by comparing flow and metabolic responses before and after infusion of an inotropic agent (dobutamine), alpha-adrenergic blockade (prazosin) and angiotensin converting enzyme inhibition (captopril). Studies in an isolated dog gracilis muscle preparation will be used to further investigate whether norepinephrine, angiotensin II and/or sodium retention impair oxygen delivery to hypoperfused exercising skeletal muscle. Gracilis muscles will be exercised at low perfusion pressures before and after infusion of norepinephrine and angiotensin II. Muscles from dogs with edematous low output failure produced by chronic rapid ventricular pacing will be similarly studied to determine if sodium retention influences skeletal muscle perfusion during exercise. It is anticipated that these studies will help to clarify the mechanisms responsible for underperfusion of working muscle during exercise in patients with heart failure and potentially may identify methods that could be used to treat this underperfusion.
