POSITRON EMISSION IMAGING OF CARDIAC SYMPATHETIC INNERVATION AND FUNCTION USING F-18 6-FLUORODOPAMINE - EFFECTS OF CHEMICAL SYMPATHECTOMY BY 6-HYDROXYDOPAMINE

Hypotheses concerning the pathophysiology of hypertension, cardiac failure and other cardiovascular disorders have imputed abnormal cardiac sympathoneural activity. Here we describe a technique to examine cardiac sympathetic innervation and function using positron emission tomographic (PET) scanning after systemic intravenous injection of F-18-6-fluorodopamine, and the effects of chemical sympathectomy by the neurotoxin, 6-hydroxydopamine (6-OHDA). Uptake of F-18-6-fluorodopamine by the heart of anesthetized dogs resulted in striking delineation of the left ventricular myocardium. Myocardial radioactivity declined bi-exponentially, with a half-life of approximately 2 h during the longer phase. In 6-OHDA-treated animals, the ventricular myocardium was barely distinguishable from the chamber; myocardial radioactivity declined rapidly and was virtually absent within 30 min after injection of F-18-6-fluorodopamine. The rates of decline in myocardial radioactivity in dogs treated with 6-OHDA were similar to those in dogs treated with reserpine, but the mechanisms of sympatholysis by these drugs were distinguished by arterial plasma levels of 6-fluorodihydroxyphenylacetic acid (6-FDOPAC). Plasma 6-FDOPAC levels were diminished in 6-OHDA-treated dogs and elevated in reserpinized dogs. The results confirm that, after injection of F-18-6-fluorodopamine, cardiac sympathetic nerve endings are radiolabeled, allowing visualization of sites of sympathetic innervation. Combined assessments of PET time-activity curves and plasma levels of metabolites of F-18-6-fluorodopamine constitute a new, potentially clinically applicable means by which to examine cardiac sympathetic function.