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Cardiac and peripheral vascular responses to adrenoceptor stimulation and blockade after cardiac transplantation
K M Borow1, A Neumann, F W Arensman
1Department of Medicine, University of Chicago Medical Center, Illinois 60637.
Insights
Cardiac transplant patients show normal contractility but increased heart rate response to dobutamine. Their hearts exhibit reduced sensitivity to alpha 1-adrenoceptor agonists, suggesting altered adrenoceptor physiology post-transplant.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Cardiac transplantation creates a unique model to study adrenoceptor physiology due to denervation and prior high catecholamine exposure.
- Understanding adrenoceptor function is crucial for managing post-transplant cardiovascular health.
Purpose of the Study:
- To investigate adrenoceptor physiology in orthotopic heart transplant recipients compared to healthy controls.
- To assess left ventricular contractility, heart rate response, and sensitivity to adrenergic agonists in transplant patients.
Main Methods:
- Simultaneous echocardiograms and carotid pulse tracings were recorded in six transplant patients and six age-matched controls.
- Left ventricular contractility was assessed using heart rate- and load-independent indexes.
- Responses to dobutamine (beta-agonist) with and without propranolol (beta-blocker) and methoxamine (alpha 1-agonist) were evaluated.
Main Results:
- No differences in baseline contractility or reserve were observed between groups.
- Transplant patients showed a significantly greater heart rate response to dobutamine.
- Dobutamine's inotropic and chronotropic effects were blocked by propranolol in both groups.
- Transplant patients exhibited reduced sensitivity to alpha 1-adrenoceptor agonist stimulation compared to controls.
Conclusions:
- Heart transplant recipients have normal left ventricular inotropic responses to beta-1 activation and blockade.
- Exaggerated chronotropic response to dobutamine and reduced sensitivity to alpha 1-adrenoceptor agonists were noted in transplant patients.
- Findings suggest differential adrenoceptor responses to long-term stimulation after cardiac transplantation.
Abstract:
A denervated heart coupled to a periphery previously exposed to high catecholamine levels provides a unique model to study adrenoceptor physiology. Six orthotopic transplant patients (1.3 +/- 0.8 years postoperative) were age matched with six atropine-treated normal subjects. Simultaneous two-dimensionally targeted left ventricular echo-cardiograms and calibrated carotid pulse tracings were recorded. Left ventricular contractility was assessed with use of heart rate- and load-independent end-systolic indexes. Studies were performed at baseline and during dobutamine infusion with and without beta-adrenergic blockade with use of propranolol; effects were assessed during afterload changes generated by the alpha 1 agonist methoxamine. There were no differences in baseline contractility or reserve between transplant patients and normal subjects. The heart rate response to dobutamine was greater for transplant patients (p less than 0.001). In both groups, the positive inotropic and chronotropic effects of dobutamine were ablated by propranolol. Dobutamine plus propranolol (unopposed alpha 1 effect) did not change mean systemic pressure in transplant patients while markedly raising mean systemic pressures in normal subjects (36 +/- 18 mm Hg; p less than 0.001). In addition, during initial challenge with methoxamine, the transplant patients required 60% more alpha 1 agonist than did the normal subjects (p less than 0.001) to obtain a pressor effect. In summary, transplant patients who were previously in severe heart failure have normal left ventricular inotropic response to beta 1 activation and blockade, exaggerated chronotropic response to dobutamine and reduced sensitivity to stimulation with alpha 1-adrenoceptor agonists. These findings are consistent with a differential response of adrenoceptors to long-term stimulation after cardiac transplantation.