No prominent role for terminal complement activation in the early myocardial reperfusion phase following cardiac surgery
No prominent role for terminal complement activation in the early myocardial reperfusion phase following cardiac surgery
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DOI：
10.1093/ejcts/ezs088
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发表时间：
2012-05-01
影响因子：
3.4
通讯作者：
Klautz, Robert J. M.
中科院分区：
文献类型：
--
作者：
Kortekaas, Kirsten A.;van der Pol, Pieter;Klautz, Robert J. M.
补体活化被认为是心肌缺血/再灌注（I/R）损伤的重要介质。尽管补体抑制剂在动物中非常有效，但临床试验未能显示对人类有实质性的益处。这就提出了关于补体激活在人心肌I/R损伤中的作用的问题。在非缺血性（n = 10）和缺血性心力衰竭（n = 10）患者以及接受心脏手术的非心力衰竭患者（n = 10）中评估可溶性C5b-9，即终末补体复合物和C5a。为了研究人类I/R损伤的病理生理学，在早期再灌注阶段的连续时间点应用再灌注心脏动静脉测量模型。此外，C3d和C5b-9沉积在再灌注前心肌和心内膜组织中被评估，并与移植前同种异体心肌移植组织进行比较。同时评估全身和心肌静脉血样本中的可溶性C5b-9和C5a显示，在所有三组患者中，再灌注心脏都没有净释放。非缺血性心力衰竭患者的活检显示C3d和C5b-9的心肌沉积最丰富：C3d是供体组织的4.8倍（P = 0.008）， C5b-9是供体组织的4.7倍（P = 0.004）。与供体相比，两组心力衰竭患者的心内膜组织中C3d含量均较高（P均= 0.02）。没有证据表明终末补体激活参与心肌再灌注后的急性期。由于补体沉积在再灌注前已经存在，人类补体抑制可能在术前阶段比在再灌注期间更有益。
Complement activation is considered an important mediator of myocardial ischaemia/reperfusion (I/R) injury. Although complement inhibitors are highly effective in animals, clinical trials fail to show a substantial benefit in humans. This raises questions on the role of complement activation in human myocardial I/R injury.Soluble C5b-9, i.e. terminal complement complex, and C5a were assessed in patients with non-ischaemic (n = 10) and ischaemic heart failure (n = 10), and patients without heart failure (n = 10) undergoing cardiac surgery. To study the pathophysiology of human I/R injury, a model of arteriovenous measurements over the reperfused heart was applied at consecutive time points during the early reperfusion phase. Furthermore, C3d and C5b-9 depositions in pre-reperfusion myocardial and endomyocardial tissue were evaluated and compared to pre-transplantation tissue from myocardial allografts.Simultaneous assessment of soluble C5b-9 and C5a in systemical and myocardial venous blood samples revealed the absence of net release from the reperfused heart in all three patient groups. Biopsies of patients with non-ischaemic heart failure showed the most abundant myocardial depositions of C3d and C5b-9: 4.8 times more C3d (P = 0.008) and 4.7 times more C5b-9 (P = 0.004) than donor tissue. Also C3d was abundantly present in endomyocardial tissue of both heart failure groups compared to donors (both P = 0.02).No evidence was obtained that terminal complement activation is involved in the acute phase following myocardial reperfusion. Since complement deposition was already present before reperfusion, human complement inhibition might be more beneficial in the preoperative phase than during reperfusion.