ELECTROPHYSIOLOGIC EFFECTS OF INTERACTIONS BETWEEN ACTIVATED CANINE NEUTROPHILS AND CARDIAC MYOCYTES

Introduction: Myocardial ischemia causes neutrophils to bind to activa ted 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 caus es PAF generation and similar changes in transmembrane potentials, Met hods and Results: Myocytes from canine left ventricle and neutrophils from the same dog were superfused with Tyrode's solution and transmemb rane 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 neutro phils was quantified with a commercial radioimmunoassay kit. Neutrophi ls activated with ZAS caused changes in myocyte transmembrane potentia ls like those induced by PAF: action potential prolongation, runs of E AD, and periods of plateau arrest, PAF receptor blockade prevented neu trophil activation from altering transmembrane potentials, Neutrophils activated with 1% ZAS liberated significant amounts of PAF, Conclusio ns: When neutrophils bound to cardiac myocytes are activated by exposu re to 1% ZAS, they cause prompt and consistent changes in myocyte elec trical activity that could be arrhythmogenic for the in situ heart, Th ese changes are similar to those caused by PAF in pharmacologic studie s, Neutrophils activated in this manner generate PAF, and the effects of their activation are prevented by blockade of PAF receptors, We con clude that, during reperfusion of ischemic myocardium, PAF generated b y activated neutrophils most likely is a cause of some arrhythmias.