Differences in norepinephrine levels in different vascular beds in congestive heart failure

Congestive heart failure is a progressive disorder of systolic and diastolic ventricular dysfunction that results in reduced forward flow and increased filling pressures. In dilated cardiomyopathy due to ischemic or nonischemic etiologies, the resultant systolic and diastolic dysfunction results in pulmonary and systemic congestion, and activation of compensatory mechanisms to help maintain blood pressure and oxygenation. 1–4 In congestive heart failure, aortic and cardiac baroreceptors are “reset” so that they lose their chronic inhibitory effect on sympathetic nerve traffic, and this results in chronic sympathetic activation and a state of vasoconstriction. 1–4 Plasma norepinephrine, a marker of sympathetic nervous system activation, 2,3 is increased in congestive heart failure and is an independent predictor of mortality. 5 Increases in plasma norepinephririe obtained from a peripheral vein have been used in several trials to examine both the effect of drug administration on neurohormonal activation and its prognostic value in predicting death in patients with heart failure. 2,5 Despite its use as a marker of sympathetic activation, it is unclear if plasma norepinephrine obtained from a peripheral vein best represents cardiac sympathetic activation or if norepinephrine obtained from other sites best represents sympathetic stimulation at the cardiac postsynaptic terminal. Because the coronary sinus drains most of the effluent from the heart, we hypothesized that coronary sinus or transmyocardial (coronary sinus — aortic) norepinephrine would best represent myocardial adrenergic stimulation. Because sudden death is increased in patients with elevated sympathetic activation, 2,4,5 and because it is unclear if systemic or cardiac sympathetic activation, or both, may be responsible for this phenomena, we believed it was important to examine which measure of norepinephrine would best reflect myocardial sympathetic activation. This is especially cogent because sympathetic activation may be different from 1 organ system to another. 6–8 Because there is no “gold standard” for myocardial adrenergic stimulation, we assumed heart rate to be a reflection of effective cardiac adrenergic activation. Because parasympathetic withdrawal is a feature of congestive heart failure, the predominant effect on heart rate would be from the sympathetic nervous system. 9