Evidence for functional sympathetic reinnervation of left ventricle and coronary arteries after orthotopic cardiac transplantation in humans

• Published in: Circulation (New York, N.Y.) Vol. 91; no. 1; pp. 72 - 78
• Main Authors: BURKE, M. N, MCGINN, A. L, HOMANS, D. C, CHRISTENSEN, B. V, KUBO, S. H, WILSON, R. F
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 1995; American Heart Association, Inc
• Subjects: Angiography; Biological and medical sciences; Blood Flow Velocity; Coronary Vessels - innervation; Coronary Vessels - physiology; Heart Transplantation - physiology; Heart Ventricles - innervation; Hemodynamics; Humans; Medical sciences; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Tyramine - pharmacology; Ventricular Function; Ventricular Function, Left; Heart; Human; Tyramine; Coronary artery; Exploration; Transplantation; Heterotransplantation; Sympathetic nervous system; Left ventricle; Treatment; Surgery; Reinnervation; Hemodynamics
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.91.1.72

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. To test directly for functional sympathetic reinnervation, we measured left ventricular or coronary hemodynamics in 11 patients < or = 4 months after transplantation, in 45 patients > or = 1 year after transplantation, and in 13 untransplanted, normally innervated patients. Sympathetic neurons were stimulated with left coronary injection of tyramine (10 micrograms/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 > or = 4 months after transplantation without reinnervation (late denervated), there was no change in left ventricular function in response to tyramine (delta 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 (delta dP/dt = 210 +/- 97 mm Hg/s; P < .05) but less than in healthy patients (delta 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 +/- 0.1 x basal, respectively; P = NS). In late reinnervated patients, CBFV fell significantly (CBFV = 0.94 +/- 0.1 x basal; P < .05). In healthy patients, CBFV fell even more (CBFV = 0.88 +/- 0.1 x basal; P < .05). 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.