Cytokines and cardiac contractile function.
Cytokines and cardiac contractile function.
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DOI：
10.1161/01.cir.95.4.778
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发表时间：
1997-02
期刊：
影响因子：
37.8
通讯作者：
R. Kelly;T. W. Smith
中科院分区：
文献类型：
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作者：
R. Kelly;T. W. Smith
对炎症细胞因子的分子和细胞生物学的理解对心血管科学家和临床医生都越来越重要。越来越多的证据表明，这些局部作用的多肽介质，或“autacoids”，发挥作用，不仅在动脉粥样硬化的发病机制和心功能不全，伴随全身性脓毒症，病毒性心肌炎，心脏移植排斥反应，但也在先进的心脏衰竭综合征导致不同的致病性侮辱。（“Autacoid”来源于希腊语autos [“自我”]和akos [“补救”];自伤素是局部作用的生物活性剂[肽和非肽]，其不同于循环中的神经递质和激素。1）25年多前，Lefer和Rovetto 2报道败血症患者和实验动物的血清含有“心肌炎因子，“其分子性质在其间的几年里一直没有得到明确的鉴定。在过去的十年中，Parrillo及其同事3 4使用完整的动物和体外分离的心脏细胞制剂系统地研究了导致全身性脓毒症心肌抑制的因素（即全身炎症反应综合征），并得出结论，TNF-α和IL-1β被证明存在于脓毒症患者的血清中，可逆性心脏抑制的可能性这些数据与早期报告一致（Levine等5综述），即活化免疫细胞调节的培养基中可溶性炎症介质改变了跳动心肌细胞对β-肾上腺素能激动剂的收缩反应，这种作用可以在该体外制剂中通过重组TNF-α或IL-1β模拟。心力衰竭患者循环和心内TNF-α水平升高的报道扩大了对这些发现的兴趣。6 7 8 9 10全身输注一种...
A working understanding of the molecular and cell biology of inflammatory cytokines is of growing importance to both cardiovascular scientists and practicing clinicians. Accumulating evidence indicates that these locally acting polypeptide mediators, or “autacoids,” play a role not only in the pathogenesis of atherosclerosis and in the cardiac dysfunction that accompanies systemic sepsis, viral myocarditis, and cardiac allograft rejection but also in advanced heart failure syndromes resulting from diverse pathogenic insults. (“Autacoid” is derived from the Greek words autos [“self”] and akos [“remedy”]; autacoids are locally acting, biologically active agents [both peptides and nonpeptides] that are distinct from neurotransmitters and hormones in the circulation.1 ) More than 25 years ago, Lefer and Rovetto2 reported that the sera of septic patients and experimental animals contained a “myocardial depressant factor,” the molecular nature of which has eluded definitive identification in the intervening years. During the past decade, Parrillo and colleagues3 4 used intact animals and in vitro isolated heart cell preparations to systematically investigate the factors that contribute to myocardial depression in systemic sepsis (ie, the systemic inflammatory response syndrome) and concluded that TNF-α and IL-1β were shown to be present in the sera of septic patients and are responsible for most, if not all, of the reversible cardiac depression often seen with this syndrome. These data are consistent with earlier reports (reviewed in Levine et al5 ) that soluble inflammatory mediators in medium conditioned by activated immunocytes altered the contractile responsiveness of beating cardiac muscle cells to β-adrenergic agonists, an effect that could be mimicked in this in vitro preparation by recombinant TNF-α or IL-1β. Interest in these findings has been amplified by reports of elevated circulating as well as intracardiac TNF-α levels in patients with heart failure.6 7 8 9 10 Systemic infusions of one …