Sympathetic dysfunction in heart failure

CHF is a common, complex and life-threatening clinical syndrome. It is widely accepted that enhanced peripheral vascular tone plays a major role in the pathophysiology of CHF. Increased activity of the sympathetic nervous system is one of the most important factors responsible for the increased afterload in CHF. This increase in sympathetic activity occurs early in the course of development of CHF. Efferent sympathetic activity is distributed in a non-uniform way in CHF, with significant increases to the heart and kidney but normal activity to some other organs such as the lung. Increased renal sympathetic activity contributes significantly to altered neural haemodynamics, sodium and water retention, and modulation of the actions of other vasoactive hormones. The regional alteration in sympathetic activity may be largely responsible for the changes in resting regional blood flow to different organs in CHF and the maldistribution of blood flow that occurs during the stress of exercise. Disordered function of cardiovascular reflexes is observed in CHF and may contribute to disordered sympathetic function. In CHF there are significant interactions between the sympathetic nervous system and other humoral systems such as the renin-angiotensin system, AVP, ANP, endothelin and renal DA. The various drugs used in the treatment of CHF have different effects on sympathetic activity: digitalis and ACE inhibitors tend to suppress activity while diuretics may have the opposite effect. Following cardiac transplantation, there is a prompt return of sympathetic function towards normal, although the heart may remain significantly denervated for a long time, with gradual reinnervation. Cyclosporin therapy tends to increase sympathetic activity and this may contribute to post-transplant hypertension.