title: Electrophysiologic effects of interactions between activated canine neutrophils and cardiac myocytes.
abstract: BACKGROUND
  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.
  
  
  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 microL, 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.
authors.affiliation: Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Hoffman
authors.forename: S J
authors.initials: SJ
authors.lastname: Feinmark
authors.forename: S D
authors.initials: SD
authors.lastname: Guo
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010972:Platelet Activating Factor / Q000096:biosynthesis; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011726:Pyridinium Compounds / Q000494:pharmacology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
chemical_list: D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C053321:CV 6209