CORRELATION BETWEEN SCINTIGRAPHIC EVIDENCE OF REGIONAL SYMPATHETIC NEURONAL DYSFUNCTION AND VENTRICULAR REFRACTORINESS IN THE HUMAN HEART

Background. Denervation supersensitivity has been proposed as a mechanism for the relation between ventricular arrhythmias and the sympathetic nervous system. Evaluation of this phenomenon in humans has become feasible only recently with the development of noninvasive scintigraphic methods for evaluating the pattern of sympathetic innervation. The purpose of this study was to determine if scintigraphic evidence of sympathetic neuronal dysfunction correlates with measurements of ventricular refractoriness and to evaluate the phenomenon of denervation supersensitivity in humans. Methods and Results. Eleven patients with a history of sustained ventricular tachycardia or sudden cardiac death who were referred for placement of an implantable defibrillator participated in this study (seven men and four women; age, 51+/-18 years). Preoperative scintigraphic evaluation of the pattern of sympathetic innervation was performed with C-11-hydroxyephedrine in conjunction with positron emission tomography. At the time of surgery, ventricular refractoriness was determined in regions of myocardium demonstrating normal and reduced C-11-hydroxyephedrine retention in the baseline state and during an infusion of norepinephrine. Scintigraphic evaluation demonstrated regions of reduced C-11-hydroxyephedrine retention in each patient. The effective refractory period in areas of myocardium that demonstrated reduced C-11-hydroxyephedrine retention was significantly longer than in areas of myocardium demonstrating normal C-11-hydroxyephedrine retention (273+/-32 versus 243+/-32 msec, p<0.001). Norepinephrine shortened the effective refractory period in regions of myocardium demonstrating normal and reduced C-11-hydroxyephedrine retention to a similar degree. Conclusions. There is a correlation between scintigraphic evidence of sympathetic neuronal dysfunction and ventricular refractoriness in the human heart. These observations help validate the use of scintigraphic techniques for evaluation of sympathetic innervation and may assist in the further evaluation of the relation between the sympathetic nervous system and ventricular arrhythmias.