(Circulation. 1995;91:72-78.)
© 1995 American Heart Association, Inc.
Articles |
Evidence for Functional Sympathetic Reinnervation of Left Ventricle and Coronary Arteries After Orthotopic Cardiac Transplantation in Humans
From the Department of Medicine, University of Minnesota (Minneapolis).
Correspondence to Robert F. Wilson, MD, Box 508 UMHC, 420 Delaware St SE, Minneapolis, MN 55455.
Background Structural sympathetic reinnervation of the transplanted human heart is believed to occur >1 year after cardiac transplantation. The functional effects of reinnervating neurons, however, are undefined.
Methods and Results To test directly for functional sympathetic
reinnervation, we measured left ventricular or coronary hemodynamics in
11 patients 
4 months after transplantation, in 45 patients 
1 year
after transplantation, and in 13 untransplanted, normally innervated
patients. Sympathetic neurons were stimulated with left coronary
injection of tyramine (10 µg/kg), which causes norepinephrine release
from intact sympathetic nerve terminals. Reinnervation was defined as a
measure of cardiac norepinephrine release after intracoronary tyramine
injection. Left ventricular pressure was measured before and at
1-minute intervals after tyramine with a micromanometer-tipped catheter
(Millar Instruments). Coronary blood flow velocity (CBFV) was measured
with a 3F Doppler catheter (Numed), and coronary artery cross-sectional
area was calculated using quantitative coronary angiography. In both
early patients and patients studied 4 months after transplantation
without reinnervation (late denervated), there was no change in left
ventricular function in response to tyramine (
dP/dt=31±61
and
49±54 mm Hg/s, respectively; P=NS). In transplant
recipients with reinnervation (late reinnervated), left ventricular
dP/dt rose significantly (dP/dt=210±97 mm Hg/s;
P<.05)
but less than in healthy patients (dP/dt=577±66 mm Hg/s;
P<.05). In both early and late denervated patients, there
was no change in CBFV in response to tyramine (CBFV=1.02±0.1 and
1.0±0.1xbasal, respectively; P=NS). In late
reinnervated
patients, CBFV fell significantly (CBFV=0.94±0.1xbasal;
P<.05). In healthy patients, CBFV fell even more
(CBFV=0.88±0.1xbasal; P<.05).
Conclusions Stimulation of reinnervating sympathetic neurons with tyramine in transplant recipients causes a significant but subnormal increase in dP/dt and a transient decrease in CBFV, suggesting that reinnervating sympathetic neurons can produce physiologically meaningful changes in left ventricular function and coronary artery tone.
Key Words: transplantation • nervous system, sympathetic • tyramine
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