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Decrease in β1- and increase in β2-adrenoceptors in long-term follow-up after orthotopic cardiac transplantation

1992; Elsevier BV; Volume: 24; Issue: 10 Linguagem: Inglês

10.1016/0022-2828(92)93182-j

1095-8584

Markus Steinfath, Heiko von der Leyen, Andreas Hecht, Klaus Neumann, Wilhelm Schmitz, Hasso Scholz, Axel Haverich, B Heublein,

Neuroscience and Neuropharmacology Research

Abstract Total β 1 - and β 2 -subtype distribution were examined in right ventricular biopsies taken from 100 patients 1–60 months after orthotopic cardiac transplantation and from eight prospective transplant donor hearts serving as controls. The patients were classified into eight groups depending on the time after transplantation that the biopsies were taken: 1–3 ( n = 15), 4–7 ( n = 15), 8–11 ( n = 6), 12 ( n = 15), 24 ( n = 15), 36 ( n = 12), 48 ( n = 12) and 60 months ( n = 10). The non-selective β-adrenoceptor antagonist (−)-[ 125 I]-iodocyanopindolol (ICYP) was used as a radioligand to assess total β-adrenoceptor density. The β 1 - and β 2 -subtype distribution was determined with a β 1 -adrenoceptor saturating concentration of the selective β 1 -adrenoceptor antagonist CGP 20712A (300 nmol/l). In transplant donor hearts the total β-adrenoceptor density was found to be 70.8 ± 7.1 fmol/mg protein including a β 1 : β 2 -adrenoceptor ratio of about 80:20%. Until 36 months after cardiac transplantation the total number of β-adrenoceptors showed no significant change. A slight but insignificant decrease was observed after 48 (16.2%) and 60 (21.2%) months. In contrast, from 12 to 60 months after cardiac transplantation the β 1 : β 2 -adrenoceptor ratio was shifted significantly (66:33% to 61:39%) as compared with transplant donor hearts which was due to an increase in β 2 - and a decrease in β 1 -adrenoceptor number. Thus, the surgically denervated, transplanted human heart exhibits a β 2 -adrenoceptor up-regulation during long-term follow-up. It is suggested that this up-regulation of the β 2 -adrenoceptor subtype could be owing to an increased importance of circulating catecholamines in modulating positive chronotropic and inotropic effects.