Functional significance of cardiac reinnervation in heart transplant recipients

Background: There is accumulating evidence of structural sympathetic reinne rvation after human cardiac transplantation. However, the functional signif icance of reinnervation in terms of exercise capacity has not been establis hed as yet; we therefore investigated the influence of reinnervation on car diopulmonary exercise testing. Methods: After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphical ly measured uptake of C-11-hydroxyephedrine (HED), lung function testing, a nd cardiopulmonary exercise testing. Two groups were defined based on scint igraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59% /min, Results: The two study groups did not show significant differences with reg ard to anthropometric data, number of rejection episodes, preoperative hemo dynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 vers us 800 +/- 1316 days, p < .05). In transplant recipients with reinnervation , heart rate at maximum exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = . 006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 ml/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 ml/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0. 24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervate d group. Conclusions: Our study results support the hypothesis that partial sympathe tic reinnervation after cardiac transplantation is of functional significan ce. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotro pic competence of the heart as well as an improved oxygen delivery to the e xercising muscles and a reduced ventilation-perfusion mismatching.