Chronic heart failure: a multisystem syndrome.

Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs: effects of cyclooxygenase inhibition. and characterization of the constitutive bovine aortic endo-thelial cell nitric oxide synthase. A comparison of the effects of vasodilator stimuli on peripheral resistance vessels in normal subjects and in patients with congestive heart failure. circulating levels of tumor necrosis factor in severe chronic heart failure. Increased levels of serum neoptenn and decreased production of neutrophil superoxide anions in chronic heart failure with elevated levels of tumor necrosis factor-alpha. necrosis factor downregulates an endothelial nitric oxide syn-thase mRNA by shortening its half-life. Enhanced basal nitric oxide production in heart failure: another failed counter-regulatory vasodilator mechanisms? Effects of L-arginine on impaired acetylcholine-induced and ischemic vasodilation of the forearm in patients with heart failure. Role of EDRF in the regulation of regional blood flow and vascular resistance at rest and during exercise in conscious dogs. Contribution of endothelium-derived relaxing factor to exercise-induced vasodilation in humans. Henderson AH. Endothelial maintenance of conduit artery distensibility is impaired in patients with congestive heart failure due to dilated cardiomyopathy. Chronic heart failure is a clinical syndrome, not a single diagnosis. Although initiated by a reduction in left ventricular function, it is characterized by substantial biochemical, hormonal, metabolic, and functional alterations in the periphery 1 ' 1. Non-cardiac factors frequently become the major determinants for both symptom generation and limitation of exercise tolerance. The microvasculature, both structurally and functionally, is disordered, leading to underper-fusion of vital organs. Even large arterial function is abnormal. Major abnormalities have been described in skeletal muscle structure, function and metabolism, including early depletion of phosphocreatinine, early acidification and accumulation of inorganic phosphate and adenosine diphosphate, and a reduction in the rate of resynthesis of phosphocreatinine' 21. It is easy to see how these changes could produce muscular fatigue! Explaining the common symptom of dyspnoea is more difficult. Putative abnormalities in lung structure and function have proved difficult to isolate convincingly; abnormal ventilatory control system function such as chemoreflex or ergoreflex overactivity may be more important' 3 ' 41 .