Parasympathetic denervation supersensitivity of the transplanted human ventricle in vivo

Sympathetic inotropic supersensitivity after transplantation-associated denervation of the cardiac autonomic nervous system has been described in humans previously. Potential changes of the parasympathetic regulation of the human ventricular contractility have not been investigated yet. We studied the antiadrenergic, negative inotropic effect of carbachol (3.6 mu g/kg) during continuous beta-adrenergic stimulation (with isoproterenol, 20 ng . kg(-1) . min(-1)) in seven heart transplant recipients and seven healthy controls. Changes in ventricular contractility were calculated as increase of the systolic pressure-to-dimension ratio (Delta P/D) and the rate-corrected velocity of circumferential fiber shortening (Delta V-cfc), using M-mode echocardiography. In the control group, the isoproterenol-induced increase in contractility was attenuated only insignificantly by carbachol [Delta P/D from 1.53 +/- 0.53 to 0.81 +/- 0.55 mmHg/mm, Delta V-cfc from 0.77 +/- 0.20 to 0.63 +/- 0.22% x root beats/min (bpm)/ms]. In contrast, the transplant group exhibited a significant reduction of the isoproterenol-induced increase in contractility [Delta P/D from 1.27 +/- 0.71 to -0.81 +/- 0.51 mmHg/mm (P < 0.01), Delta V-cfc from 1.04 +/- 0.84 to 0.04 +/- 0.43% 0.43% x root bpm/ms (P < 0.01)]. These data are consistent with parasympathetic indirect negative inotropic supersensitivity of the transplanted human heart in vivo.