Ventricular myocytes isolated from rejecting cardiac allografts exhibit a reduced beta-adrenergic contractile response.
Previous experiments using multicellular preparations from rejecting transplanted animal hearts have indicated that a decrease in the contractile response to beta-adrenergic stimulation accompanies acute rejection. The precise mechanism of this decreased beta-adrenergic response, which may limit the inotropic reserve in human transplant patients during rejection, is currently unknown. In order to determine whether the decreased beta-adrenergic response is an intrinsic property of the cardiac myocytes from rejecting hearts, we examined the effects of beta-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 beta-adrenergic contractile response is an intrinsic property of the rejecting cardiac myocyte.
Pyo
R T
RT
Department of Physiology and Biophysics, University of Illinois at Chicago 60612-7342, USA.
Wahler
G M
GM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D006084:Graft Rejection / Q000503:physiopathology*; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous / Q000502:physiology
D000318:Adrenergic beta-Agonists