Reduced exercise tolerance in chronic heart failure and its relationship to neurohumoral factors.

There is some evidence that exercise intolerance in chronic heart failure is linked to the activity of compensatory mechanisms, including neurohumoral factors. However, there is a lack of correlation between exercise capacity and the degree of LV-dysfunction in this setting. Impaired skeletal muscle perfusion during exercise appears to be involved in reduced exercise capacity in patients with heart failure. The peripheral vasoconstriction mediated by increased sympathetic tone and activated plasma renin-angiotensin-aldosterone system (RAAS) may act primarily for short-term control and its short-term inhibition does not restore exercise capacity. The effects of the vascular RAS, impaired flow-dependent endothelium-mediated dilation (e.g. due to chronically reduced flow) and structural alterations of the vessel wall only slowly emerge over time. In addition, fluid retention may contribute to increased vascular stiffness in chronic heart failure. Improved cardiac output with acute administration of vasodilators and inotropes is not immediately translated into increased flow to skeletal muscle, because (1) the reversal of the above delineated peripheral alterations develops slowly over time; such agents given acutely may cause redistribution of blood flow in skeletal muscle without improving oxygen availability, (2) intrinsic abnormalities of skeletal muscle exist in chronic heart failure; e.g. due to chronic deconditioning, resulting in reduced oxidative capacity of skeletal muscle, as suggested by ultrastructural analysis and NMR-spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)