Morawietz H, Szibor M, Goettsch W, Bartling B, Barton M, Shaw S, Koerfer R, Zerkowski H R, Holtz J
Institute of Pathophysiology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
Circulation. 2000 Nov 7;102(19 Suppl 3):III188-93. doi: 10.1161/01.cir.102.suppl_3.iii-188.
Ventricular assist devices (VAD) are implanted in patients with end-stage heart failure for bridging the time until heart transplantation, resulting in hemodynamic unloading of the failing heart, improved cardiac contractile and mitochondrial function, and reversal of cardiac hypertrophy. It is unknown whether VAD unloading may affect the cardiac endothelin (ET) system, which has been proposed as one of the putative pathomechanisms of heart failure.
With the use of standard-calibrated, competitive reverse-transcription-polymerase chain reaction mRNA expression of components of the ET system was analyzed in left ventricular myocardium from nonfailing donor hearts, from failing hearts without and with ACE inhibitor therapy, and from patients with end-stage heart failure at the time of VAD implantation and 103+/-15 days after VAD implantation during removal with subsequent heart transplantation. ET receptor A (ET(A)) was markedly upregulated in failing human myocardium. This increased ET(A) expression was not affected by ACE inhibitor treatment but was normalized by VAD unloading. ET(A) expression before or after VAD implantation did not correlate with duration of VAD implantation or suppression of Pro-ANP mRNA. ET(B) mRNA expression was unaffected by heart failure or VAD. In contrast, increased ET-converting enzyme-1 mRNA and ET-1 peptide levels in failing myocardium were partially normalized by ACE inhibition but not by VAD unloading.
We conclude that VAD implantation normalizes ET(A) expression in failing human left ventricular myocardium, probably as the result of the beneficial effects of VAD unloading.
心室辅助装置（VAD）植入终末期心力衰竭患者体内，用于在心脏移植前的这段时间进行过渡，从而实现衰竭心脏的血流动力学卸载，改善心脏收缩功能和线粒体功能，并逆转心脏肥大。目前尚不清楚VAD卸载是否会影响心脏内皮素（ET）系统，该系统被认为是心力衰竭的潜在发病机制之一。
使用标准校准的竞争性逆转录聚合酶链反应，分析了ET系统各组分在以下几种心脏左心室心肌中的mRNA表达：非衰竭供体心脏、未接受和接受ACE抑制剂治疗的衰竭心脏、VAD植入时的终末期心力衰竭患者以及VAD植入103±15天后在移除装置并随后进行心脏移植时的患者。ET受体A（ET(A)）在衰竭的人类心肌中显著上调。这种ET(A)表达的增加不受ACE抑制剂治疗的影响，但通过VAD卸载恢复正常。VAD植入前后的ET(A)表达与VAD植入持续时间或Pro-ANP mRNA的抑制无关。ET(B) mRNA表达不受心力衰竭或VAD的影响。相反，衰竭心肌中ET转换酶-1 mRNA和ET-1肽水平的升高通过ACE抑制部分恢复正常，但未通过VAD卸载恢复正常。
我们得出结论，VAD植入可使衰竭的人类左心室心肌中的ET(A)表达恢复正常，这可能是VAD卸载有益作用的结果。
