PO-455617-6 FUNCTIONAL CONSEQUENCES OF SYMPATHETIC NEURAL REMODELING IN PREMATURE VENTRICULAR CONTRACTION-INDUCED CARDIOMYOPATHY REVEALED BY DUAL STRESSOR PVC AND EXERCISE CHALLENGE

Abstract

A common presentation of PVC-induced cardiomyopathy (PVC-CM) is exertional fatigue and dyspnea without overt heart failure. The sympathetic nervous system is an adaptive mechanism that augments the cardiac response to an external stressor such as PVCs. We hypothesize that one mechanism of exercise intolerance in PVC-CM is due to the inability of the remodeled sympathetic nervous system maximally recruited from chronic frequent PVC exposure to further augment in response to exercise challenge. To assess the sympathetic neural response to exercise in the presence or absence of PVCs, during baseline state and after development of PVC-CM. In 8 canines, we implanted pacemakers to administer bigeminal PVCs at 200ms coupling for 12-weeks to induce PVC-CM and radio-telemetry device to record ambulatory ECG and nerve activity from the left stellate ganglion nerve (SNA). In order to assess the sympathetic nerve response to exercise (exercise - rest SNA), we subjected animals to the “dual stressor” of a 9-minute exercise tolerance test (ETT, 1.1-3.3mph) in SR and in the presence of bigeminal PVCs (200ms coupling), at baseline (before 12-week PVC exposure) and after development of PVC-CM (after 12-week PVC exposure). SNA (Figure 1A) was significantly increased during exercise compared with rest in all groups except when exercise was performed in presence of PVCs in PVC-CM (CMPVC). The absolute increase in SNA with exercise (exercise-rest SNA) (Figure 1B) was significantly greater in the presence of PVCs compared with SR at baseline but this was reversed in PVC-CM, i.e., significantly less in the presence of PVCs compared with SR. In PVC-CM, the % increase in SNA with exercise (Figure 1C) was less than at baseline, particularly in the presence of PVCs. In PVC-CM, there is generalized sympathetic upregulation but also a failure to further augment the sympathetic response response to exercise, most likely because of maximally recruited nerve endings from chronic frequent PVC perturbation. This data could explain exercise intolerance observed in patients with PVC-CM and suggest that exercise testing could be a useful tool in the clinical assesment of patients with PVC-CM.