Ventricular myocytes isolated from rejecting cardiac allografts exhibit a reduced β-adrenergic contractile response

. Ventricular Myocytes Isolated from Rejecting Cardiac Allografts Exhibit a Reduced β-Adrenergic Contractile Response. Journal of Molecular and Cellular Cardiology (1995) 27, 773–776. Previous experiments using multicellular preparations from rejecting transplanted animal hearts have indicated that a decrease in the contractile response to β-adrenergic stimulation accompanies acute rejection. The precise mechanism of this decreased β-adrenergic response, which may limit the inotropic reserve in human transplant patients during rejection, is currently unknown. In order to determine whether the decreased β-adrenergic response is an intrinsic property of the cardiac myocytes from rejecting hearts, we examined the effects of β-adrenergic stimulation (isoproterenol, 10−8 and 10−6 M) on the cell shortening of single myocytes isolated from native rat hearts (untransplanted Lewis strain), non-rejecting isografts (Lewis to Lewis heterotopic transplant), and rejecting allografts (Lewis to ACI transplant). The myocytes from isografts demonstrated a significantly increased contractile response to isoproterenol compared to native myocytes (presumably due to denervation supersensitivity), whereas the myocytes from allografts demonstrated a greatly decreased response to isoproterenol compared to both native and isograft myocytes. These results demonstrate that the decreased β-adrenergic contractile response is an intrinsic property of the reiecting cardiac myocyte.