Evidence for functional sympathetic reinnervation of left ventricle and coronary arteries after orthotopic cardiac transplantation in humans
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 cor...
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Published in | Circulation (New York, N.Y.) Vol. 91; no. 1; pp. 72 - 78 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Hagerstown, MD
Lippincott Williams & Wilkins
1995
American Heart Association, Inc |
Subjects | |
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Abstract | 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. |
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AbstractList | BACKGROUNDStructural 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 RESULTSTo 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).CONCLUSIONSStimulation 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. 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 (ΔdP/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 (ΔdP/dt=210±97 mm Hg/s; P <.05) but less than in healthy patients (ΔdP/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×basal, respectively; P =NS). In late reinnervated patients, CBFV fell significantly (CBFV=0.94±0.1×basal; P <.05). In healthy patients, CBFV fell even more (CBFV=0.88±0.1×basal; 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. 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. |
Author | HOMANS, D. C BURKE, M. N WILSON, R. F KUBO, S. H MCGINN, A. L CHRISTENSEN, B. V |
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Keywords | Heart Human Tyramine Coronary artery Exploration Transplantation Heterotransplantation Sympathetic nervous system Left ventricle Treatment Surgery Reinnervation Hemodynamics |
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Snippet | Structural sympathetic reinnervation of the transplanted human heart is believed to occur > 1 year after cardiac transplantation. The functional effects of... Background Structural sympathetic reinnervation of the transplanted human heart is believed to occur >1 year after cardiac transplantation. The functional... BACKGROUNDStructural sympathetic reinnervation of the transplanted human heart is believed to occur > 1 year after cardiac transplantation. The functional... |
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SubjectTerms | 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 |
Title | Evidence for functional sympathetic reinnervation of left ventricle and coronary arteries after orthotopic cardiac transplantation in humans |
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