Absence of parasympathetic control of heart rate after human orthotopic cardiac transplantation.

Abstract

Partial reinnervation of cardiac sympathetic nerves has been observed after heart transplantation; we hypothesized that parasympathetic control to the heart after transplantation may return as well. To test this hypothesis, we examined heart rate responses produced by two cardiovascular reflexes whose efferent limbs are subserved by vagal fibers to the heart: (1) trigeminal reflex (simulated diving reflex) and (2) arterial baroreflex with phenylephrine injection. An "early" group (n=31, <24 months after transplantation) and a "late group" (n=27, >45 months after transplantation) were studied and compared with a control group with intact cardiac innervation (n=32) and a renal transplant group with similar transplant immunosuppressive regimen (n=11). For trigeminal reflex testing, responses of the donor sinus node (DSN) (sinus node controlling heart rate) and recipient sinus node (RSN) in the innervated remnant right atrium in cardiac transplant patients were compared with heart rate responses in the control groups. For arterial baroreflex testing, baroreflex gains for the DSN and RSN in the cardiac transplant groups were compared with those of the control group. With engagement of the trigeminal reflex, the DSN rate of both transplant groups changed minimally (early, 1.2+/-1.2 bpm; late, 1.8+/-2.5 bpm) compared with the expected decrease in control subjects (-19.8+/-3.0 bpm) and renal transplant patients (-23.9+/-4.9 bpm) (P<.001 versus cardiac transplants). Changes in the RSN rate of both cardiac transplant groups (early, -13.0+/-4.0 bpm; late, -10.0+/-3.7 bpm) were similar to the control groups. Arterial baroreflex gains for the DSN were also depressed (early, 0.1+/-0.2 ms/mm Hg; late, 0.2+/-0.2 ms/mm Hg) compared with control (14.9+/-1.8 ms/mm Hg) and RSN (early, 9.9+/-1.3 ms/mm Hg; late, 10.9+/-1.3 ms/mm Hg; P<.001 versus DSN transplant). These data suggest that parasympathetic influences on donor heart rate are absent in the majority of patients up to 96 months after cardiac transplantation.