Effects of autonomic neuropathy on coronary blood flow in patients with diabetes mellitus

Background-Cardiac sympathetic signals play an important role in the regulation of myocardial perfusion. We hypothesized that sympathetically mediated myocardial blood flow would be impaired in diabetics with autonomic neuropathy. Methods ana Results-We studied 28 diabetics (43+/-7 years old) and 11 age-matched healthy volunteers. PET was used to delineate cardiac sympathetic innervation with [C-11]hydroxyephedrine ([C-11]HED) and to measure myocardial blood flow at rest, during hyperemia, and in response to sympathetic stimulation by cold pressor testing. The response to cardiac autonomic reflex tests was also evaluated. Using ultrasonography, we also measured brachial artery reactivity during reactive hyperemia (endothelium-dependent dilation) and after sublingual nitroglycerin (endothelium-independent dilation). Based on [C-11]HED PET, 13 of 28 diabetics had sympathetic-nerve dysfunction (SND). Basal flow was regionally homogeneous and similar in the diabetic and normal subjects. During hyperemia, the increase in flow was greater in the normal subjects (284+/-88%) than in the diabetics with SND (187+/-80%, P=0.084) and without SND (177+/-72%, P=0.028). However, the increase in flow in response to cold was lower in the diabetics with SND (14+/-10%) than in those without SND (31+/-12%) (P=0.015) and the normal subjects (48+/-24%) (P<0.001). The flow response to cold was related to the myocardial uptake of [C-11]HED (P<0.001). Flow-mediated brachial artery dilation was impaired in the diabetics compared with the normal subjects, but it was similar in the diabetics with and without SND. Conclusions-Diabetic autonomic neuropathy is associated with an impaired vasodilator response of coronary resistance vessels to increased sympathetic stimulation, which is related to the degree of SND.