Isolated Presynaptic Inotropic j3-Adrenergic Supersensitivity of the Transplanted Denervated Human Heart In Vivo

Background. The regulation of contractility of the transplanted heart depends on circulating catecholamines resulting from cardiac denervation. Supersensitivity to circulating catecholamines may result from loss of presynaptic neuronal uptake or upregulation of postsynaptic (adrenergic receptors. Methods and Results. Dose-response curves using the j3-adrenergic receptor agonists isoprenaline (no neuronal uptake) and epinephrine (neuronal uptake) were performed in vivo. The inotropic response was measured echocardiographically as the increase of fractional shortening (AFS) and the increase of the systolic pressure/dimension ratio (AP/D). The inotropic response to increasing doses of isoprenaline (5-20 ng/kg* min) was identical in 36 heart transplant recipients compared with 13 control subjects: AFS during 20 ng/kg * min isoprenaline amounted to 18.2±6.2% versus 17.4±4.0%o (NS) and AP/D to 2.3+±1.2