Effects of Cardiac Sympathetic Innervation on Coronary Blood Flow

Abstract

Background: The role of cardiac sympathetic nerves in regulating coronary blood flow is controversial. We sought to determine the degree to which cardiac efferent sympathetic signals modulate coronary blood flow. The heterogeneous sympathetic reinnervation in transplanted hearts provides a model for studying the vasomotor responses to adrenergic stimulation in reinnervated and denervated coronary territories of the same heart. Methods: We studied 14 cardiac-transplant recipients who had normal coronary arteries and no evidence of rejection and 8 normal subjects. We used positron-emission tomography with [11C]hydroxyephedrine, an analogue of norepinephrine, to delineate sympathetic innervation. Using [13N]ammonia, we measured myocardial blood flow at rest, during adenosine-induced hyperemia, and in response to sympathetic stimulation induced by cold pressor testing. Results: In the transplant recipients, the uptake of [11C]hydroxyephedrine was greater in the territory served by the left anterior descending artery (mean±SE, 0.15±0.01) than in those served by the right coronary artery (0.07±0.01, P<0.001) or the circumflex artery (0.09±0.01, P<0.001). The basal flow was similar in all three regions, as was the percent increase in flow during hyperemia. However, the increase in flow in response to cold pressor testing was higher in the territory of the left anterior descending artery (46±10 percent) than in those of the right coronary artery (16±6 percent, P=0.01) or the circumflex artery (23±6 percent, P=0.06), although the changes in hemodynamics and levels of circulating catecholamines were similar. No such regional differences were observed in the normal subjects. Conclusions: Increases in coronary blood flow in response to sympathetic stimulation correlated with the regional norepinephrine content in the cardiac sympathetic-nerve terminals. These findings suggest that cardiac adrenergic signals play an important part in regulating myocardial blood flow.