Evidence Against Reinnervation of Cardiac Vagal Afferents After Human Orthotopic Cardiac Transplantation

Abstract

Background Orthotopic cardiac transplantation results in total cardiac denervation. Recent studies in humans suggest that reinnervation of cardiac sympathetic nerves (cardiac efferents) may occur after cardiac transplantation. We hypothesized that reinnervation of cardiac afferents may occur as well. To test this hypothesis, we investigated reflex responses produced by stimulation of ventricular chemosensory endings subserved by vagal afferents (cardiac depressor reflex). Methods and Results Two cardiac transplant groups were studied: an “early” group (n=18, <24 months after transplant) and a “late” group (n=18, >43 months after transplant); these groups were compared with a control group with intact innervation (n=18). The reflex response of the recipient sinus node (RSN) in the remnant right atrium, which remains innervated after transplantation, was observed during selective right coronary artery (RCA) and left coronary artery (LCA) injection of the radiographic contrast agent meglumine diatrizoate, which is known to stimulate ventricular chemosensory endings. A decrease in the rate of the RSN was expected if reinnervation of chemosensory endings had occurred and the afferent limb of the cardiac depressor reflex was intact. With injection, the RSN rate of both transplant groups did not decrease but increased (early: LCA, 7.2±1.4 beats per minute; RCA, 6.3±1.3 beats per minute; late: LCA, 5.9±1.0 beats per minute; RCA, 6.0±0.9 beats per minute) compared with the expected decrease in control patients (LCA, −20.8±2.5 beats per minute; RCA, −18.0±4.0 beats per minute; P <.001 versus transplants). Decreases in mean arterial pressure in the transplant groups (early: LCA, −11.3±1.4 mm Hg; RCA, −10.0±1.6 mm Hg; late: LCA, −13.0±1.6 mm Hg; RCA, −9.1±1.5 mm Hg) were less than those observed in the control group (LCA, −19.8±2.2 mm Hg; RCA, −18.7±4.0 mm Hg; P <.05 versus transplants). Conclusions The results suggest that reinnervation of ventricular chemosensory endings subserved by vagal afferents in cardiac transplant patients does not occur up to 74 months after transplantation.