Chester M R, Amadi A A, Barnett D B
National Heart and Lung Institute, London.
Br Heart J. 1995 Jun;73(6):540-3. doi: 10.1136/hrt.73.6.540.
Failure of the donor (graft) heart is the main cause of mortality in the first month after orthotopic cardiac transplantation. In a preliminary study marked downregulation of cardiac beta adrenoceptor density was found in apparently normal donor hearts of recipients who developed severe cardiac failure soon after implantation. Cardiac beta adrenoceptors are an important factor in the development of cardiac failure in the human heart. The aim of this study therefore was to determine whether fatal graft failure in the first month after transplantation is associated with downregulation of beta adrenoceptor density in the donor heart.
Right ventricular endomyocardial biopsy specimens were taken from consecutive adult donor patients immediately before implantation. A previously described radioligand binding method was used to determine beta adrenoceptor density in consecutive patients who developed fatal graft failure and died within 1 month of transplantation and in a group of control donors transplanted during the same period.
Perioperative fatal graft failure developed in 13 patients. Forty one specimens from donor hearts that were transplanted into recipients who did not develop fatal graft heart failure formed the control group. There were no systematic differences in donor or recipient characteristics between the graft heart failure and control groups. In particular donor catecholamine requirement and recipient pulmonary vascular resistance did not differ between groups. Total beta adrenoceptor density was reduced in the fatal graft heart failure group compared with that in the controls (13.4 (7) fmol/mg v 21 (7) fmol/mg; P < 0.01). There was a positive correlation between beta adrenoceptor density in the donor heart and time to death in the graft heart failure group (r2 = 0.3, P < 0.05). The beta adrenoceptor binding affinity (Kd) did not differ between the graft failure group and the controls (47 (6) pM v 44 (7) pM).
The development of perioperative fatal cardiac failure after orthotopic cardiac transplantation is associated with downregulation of beta adrenoceptors in the donor heart before implantation.
供体(移植)心脏衰竭是原位心脏移植后第一个月内死亡的主要原因。在一项初步研究中,发现植入后很快发生严重心力衰竭的受者的明显正常供体心脏中,心脏β肾上腺素能受体密度显著下调。心脏β肾上腺素能受体是人类心脏心力衰竭发生发展的一个重要因素。因此,本研究的目的是确定移植后第一个月内致命性移植失败是否与供体心脏β肾上腺素能受体密度下调有关。
在植入前,从连续的成年供体患者中获取右心室心内膜活检标本。采用先前描述的放射性配体结合方法,测定连续发生致命性移植失败并在移植后1个月内死亡的患者以及同期移植的一组对照供体中的β肾上腺素能受体密度。
13例患者发生围手术期致命性移植失败。将41例来自未发生致命性移植心脏衰竭受者的供体心脏标本作为对照组。移植心脏衰竭组和对照组在供体或受者特征方面没有系统性差异。特别是,两组之间供体儿茶酚胺需求量和受者肺血管阻力没有差异。与对照组相比,致命性移植心脏衰竭组的总β肾上腺素能受体密度降低(13.4(7)fmol/mg对21(7)fmol/mg;P<0.01)。移植心脏衰竭组中,供体心脏β肾上腺素能受体密度与移植心脏死亡时间呈正相关(r2 = 0.3,P<0.05)。移植失败组和对照组之间的β肾上腺素能受体结合亲和力(Kd)没有差异(47(6)pM对44(7)pM)。
原位心脏移植后围手术期致命性心力衰竭的发生与植入前供体心脏β肾上腺素能受体下调有关。