Cardiac dysfunction caused by purified human C3a anaphylatoxin.
Cardiac dysfunction caused by purified human C3a anaphylatoxin.
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纯化的人 C3a 过敏毒素引起的心脏功能障碍。
DOI：
10.1073/pnas.82.3.886
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发表时间：
1985
影响因子：
11.1
通讯作者：
Polley,MJ
中科院分区：
文献类型：
--
作者：
delBalzo,UH;Levi,R;Polley,MJ
鉴于补体激活可能导致心功能障碍，本研究旨在确定补体衍生C3a过敏毒素的心脏效应。通过冠状动脉内推注将纯化的人C3a给予离体豚鼠心脏。作为剂量的函数，C3a引起心动过速、房室传导受损、左心室收缩衰竭、冠状血管收缩和组胺释放。羧肽酶B裂解羧基末端精氨酸可消除这些效应。C3a诱导的心动过速的幅度与释放到冠状流出物中的内源性心脏组胺的量相关。而心动过速显着减少组胺H2拮抗剂西咪替丁，收缩衰竭和冠状动脉收缩引起的C3a的白三烯拮抗剂FPL 55712和环氧合酶抑制剂吲哚美辛，分别拮抗。这表明组胺、白三烯和血管活性前列腺素酸可能介导C3a的各种心脏效应。我们的研究结果表明，C3a过敏毒素有显着的心脏效应的浓度，很可能达到一定程度的C3激活常见于各种疾病状态。因此，我们的数据与过敏毒素的产生可能在临床条件下诱导心功能障碍的假设是一致的。
The purpose of this investigation was to define the cardiac effects of complement-derived C3a anaphylatoxin, in view of the possibility that cardiac dysfunction may occur as a result of complement activation. Purified human C3a was administered by intracoronary bolus injections into isolated guinea pig hearts. As a function of dose, C3a caused tachycardia, impairment of atrioventricular conduction, left ventricular contractile failure, coronary vasoconstriction, and histamine release. These effects were abolished by cleavage of the COOH-terminal arginine by carboxypeptidase B. The magnitude of C3a-induced tachycardia correlated with the amount of endogenous cardiac histamine released into the coronary effluent. Whereas the tachycardia was markedly reduced by the histamine H2 antagonist cimetidine, the contractile failure and the coronary vasoconstriction caused by C3a were antagonized by the leukotriene antagonist FPL 55712 and by the cyclooxygenase inhibitor indomethacin, respectively. This suggests that histamine, leukotrienes, and vasoactive prostanoates may mediate the various cardiac effects of C3a. Our findings indicate that C3a anaphylatoxin has marked cardiac effects at concentrations that are likely to be attained with a degree of C3 activation commonly seen in various disease states. Thus, our data are compatible with the hypothesis that generation of anaphylatoxins may induce cardiac dysfunction in clinical conditions.