Scintigraphic Assessment of Regionalized Defects in Myocardial Sympathetic Innervation and Blood Flow Regulation in Diabetic Patients With Autonomic Neuropathy

Objectives. This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions.

Background. Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown.

Methods. We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 μg/kg body weight per min).

Results. Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 ± 29 ml/100 g per min) than in either the nondiabetic (69 ± 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 ± 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 ± 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 ± 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments.

Conclusions. DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.