Electrophysiologic effects of interactions between activated canine neutrophils and cardiac myocytes
Electrophysiologic effects of interactions between activated canine neutrophils and cardiac myocytes
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DOI：
10.1111/j.1540-8167.1997.tb01831.x
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发表时间：
1997-06-01
影响因子：
2.7
通讯作者：
Guo, SD
中科院分区：
文献类型：
--
作者：
Hoffman, BF;Feinmark, SJ;Guo, SD
简介：心肌缺血导致中性粒细胞与活化的肌细胞结合并释放血小板活化因子（PAF）， PAF导致复极延迟、后去极化早期（EADs）和复极化停止。我们研究了与犬心肌细胞结合的中性粒细胞的活化作用，以确定这种活化是否导致PAF的产生和跨膜电位的类似变化。将犬左心室肌细胞和同一犬的中性粒细胞与Tyrode溶液混合，记录其跨膜电位，加入中性粒细胞（100 μ L, 10(6)/mL）并与肌细胞结合，中性粒细胞用1%酶酶活性血清（ZAS）活化，CV-6209 （100 nM）阻断PAF受体，活化的中性粒细胞释放PAF用商业放射免疫测定试剂盒定量。被ZAS激活的中性粒细胞引起肌细胞跨膜电位的变化，与PAF诱导的相似：动作电位延长，EAD发作，高原停搏期，PAF受体阻断阻止中性粒细胞激活改变跨膜电位，1%的ZAS激活的中性粒细胞释放了大量的PAF。当与心肌细胞结合的中性粒细胞在暴露于1%的ZAS下被激活时，它们会引起肌细胞电活动的迅速和一致的变化，这些变化可能导致原位心脏心律失常，这些变化与药理学研究中PAF引起的变化相似，以这种方式激活的中性粒细胞产生PAF，并且通过阻断PAF受体来阻止它们的激活作用。由活化的中性粒细胞产生的PAF很可能是一些心律失常的原因。
Introduction: Myocardial ischemia causes neutrophils to bind to activated myocytes and liberate platelet-activating factor (PAF), PAF causes delayed repolarization, early afterdepolarizations (EADs), and arrest of repolarization, We studied the effect of activation of neutrophils bound to canine cardiac myocytes to determine if such activation causes PAF generation and similar changes in transmembrane potentials,Methods and Results: Myocytes from canine left ventricle and neutrophils from the same dog were superfused with Tyrode's solution and transmembrane potentials recorded from the former, Neutrophils (100 mu L, 10(6)/mL) were added and allowed to bind to the myocytes, Neutrophils were activated with 1% zymosan-activated serum (ZAS), CV-6209 (100 nM) was used to block receptors for PAF, Liberation of PAF by activated neutrophils was quantified with a commercial radioimmunoassay kit. Neutrophils activated with ZAS caused changes in myocyte transmembrane potentials like those induced by PAF: action potential prolongation, runs of EAD, and periods of plateau arrest, PAF receptor blockade prevented neutrophil activation from altering transmembrane potentials, Neutrophils activated with 1% ZAS liberated significant amounts of PAF,Conclusions: When neutrophils bound to cardiac myocytes are activated by exposure to 1% ZAS, they cause prompt and consistent changes in myocyte electrical activity that could be arrhythmogenic for the in situ heart, These changes are similar to those caused by PAF in pharmacologic studies, Neutrophils activated in this manner generate PAF, and the effects of their activation are prevented by blockade of PAF receptors, We conclude that, during reperfusion of ischemic myocardium, PAF generated by activated neutrophils most likely is a cause of some arrhythmias.