Arrhythmias caused by platelet activating factor

被引:44
作者
Hoffman, BF
Guo, SD
Feinmark, SJ
机构
[1] Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY
[2] Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032
关键词
platelet activating factor; neutrophils; ischemia reperfusion; arrhythmias; early afterdepolarizations;
D O I
10.1111/j.1540-8167.1996.tb00507.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: Both ischemia and reperfusion are associated with ventricular arrhythmias. In both instances, neutrophils migrate into the ischemic zone, are activated by locally released factors, and bind to myocytes, The activated neutrophils liberate platelet activating factor (PAF), We have studied the arrhythmogenic actions of PAF on transmembrane potentials of isolated canine cardiac myocytes. Methods and Results: Cardiac myocytes were prepared from normal canine hearts by standard methods and studied in vitro by recording transmembrane potentials under control conditions and during exposure to graded doses of PAF, usually 0.25 to 1.25 mu g (0.25 to 1.2 mu M), Myocytes were superfused with Tyrode's solution (2.0 mL/min), paced at a cycle length of 1000 msec, and maintained at a temperature between 36 degrees and 38 degrees C, PAF caused a consistent and dose-dependent set of alterations in the transmembrane potential, including increased action potential duration, runs of early afterdepolarizations (EADs), and transient arrest of repolarization (PA), In addition, in some myocytes PAF caused intermittent small depolarizations both at the plateau voltage and resting potential, The effects of PAF were transient: only some residual action potential prolongation was noted after Tyrode's washout for 5 minutes, Effects of PAF were blocked in a dose-dependent manner by the PAF receptor antagonist, CV-6209, Both tetrodotoxin (1.2 X 10(-6) M) and xylocaine (5 X 10(-5) M) antagonized the ability of PAF to cause EADs and PA. Conclusions: PAF consistently exerts arrhythmogenic effects on the membrane of ventricular myocytes, Since PAF is liberated by activated neutrophils and since activated neutrophils migrate into ischemic myocardium on reperfusion, we judge that PAF liberated by such neutrophils is an important arrhythmogenic factor for reperfusion arrhythmias. The same mechanism may be a cause of arrhythmias during the evolution of infarction.
引用
收藏
页码:120 / 133
页数:14
相关论文
共 51 条
[41]  
SQUADRITO F, 1993, J LIPID MEDIATOR, V8, P53
[42]  
TAMURA K, 1994, CORONARY ARTERY DIS, V5, P267
[43]  
TERASHITA ZI, 1987, J PHARMACOL EXP THER, V242, P263
[44]  
TESSNER TG, 1989, J BIOL CHEM, V264, P4794
[45]   VENTRICULAR-FIBRILLATION CAUSED BY MYOCARDIAL REPERFUSION IN PRINZMETALS ANGINA [J].
TZIVONI, D ;
KEREN, A ;
GRANOT, H ;
GOTTLIEB, S ;
BENHORIN, J ;
STERN, S .
AMERICAN HEART JOURNAL, 1983, 105 (02) :323-325
[46]   INWARD SODIUM CURRENT AT RESTING POTENTIALS IN SINGLE CARDIAC MYOCYTES INDUCED BY THE ISCHEMIC METABOLITE LYSOPHOSPHATIDYLCHOLINE [J].
UNDROVINAS, AI ;
FLEIDERVISH, IA ;
MAKIELSKI, JC .
CIRCULATION RESEARCH, 1992, 71 (05) :1231-1241
[47]   REPERFUSION ARRHYTHMIAS - ROLE OF EARLY AFTERDEPOLARIZATIONS STUDIED BY MONOPHASIC ACTION-POTENTIAL RECORDINGS IN THE INTACT CANINE HEART DURING AUTONOMICALLY DENERVATED AND STIMULATED STATES [J].
VERA, Z ;
PRIDE, HP ;
ZIPES, DP .
JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, 1995, 6 (07) :532-543
[48]  
WIT AL, 1993, VENTRICULAR ARRHYTHM
[49]   INFLUENCE OF LONG-CHAIN ACYLCARNITINES ON VOLTAGE-DEPENDENT CALCIUM CURRENT IN ADULT VENTRICULAR MYOCYTES [J].
WU, JY ;
CORR, PB .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (02) :H410-H417
[50]   HYPOXIC STRESS INDUCES CARDIAC MYOCYTE-DERIVED INTERLEUKIN-6 [J].
YAMAUCHITAKIHARA, K ;
IHARA, Y ;
OGATA, A ;
YOSHIZAKI, K ;
AZUMA, J ;
KISHIMOTO, T .
CIRCULATION, 1995, 91 (05) :1520-1524