Sympathetic reinnervation of the sinus node and exercise hemodynamics after cardiac transplantation

Background - Sympathetic cardiac reinnervation occurs variably after cardiac transplantation (CT) in humans. We hypothesized that sinus node reinnervation would partially restore normal chronotropic response to exercise. Methods and Results - Thirteen recent CT recipients, 28 late CT recipients (≥ 1 year after CT), and 20 control subjects were studied. Sinus node sympathetic reinnervation was determined by heart rate (HR) change after tyramine injection into the artery that perfused the sinus node. HR changes of < 5 and ≥ 15 bpm were defined, respectively, as denervation and marked reinnervation. During treadmill exercise, HR, blood pressure, and expired O₂ and CO₂ were measured. All early transplant recipients exhibited features typical of denervation (basal HR, 88 ± 2 bpm; peak HR, 132 ± 4 bpm, peaking 1.8 ± 0.3 minutes after exercise cessation and slowly declining after exercise). A similar pattern was found in the 12 late transplant recipients with persistent sinus node denervation. However, in patients with marked reinnervation, exercise HR rose more (peak HR, 142 ± 4 and 141 ± 2 bpm), peaked earlier after cessation of exercise (0.7 ± 0.4 and 0.3 ± 0.1 minute), and fell more rapidly. Exercise duration and maximal oxygen consumption were not related significantly to reinnervation status, but a trend existed for longer exercise time in markedly reinnervated patients. Conclusions - The present studies suggest that sympathetic reinnervation of the sinus node is accompanied by partial restoration of normal HR response to exercise. Both maximal oxygen consumption and exercise duration were markedly shorter in CT patients than in control subjects, and most of the difference was not related to innervation status.