Acetyl glyceryl ether phosphorylcholine (AGEPC). A putative mediator of cardiac anaphylaxis in the guinea pig

R. Levi, J. A. Burke, Z. G. Guo, Y. Hattori, C. M. Hoppens, L. M. McManus, D. J. Hanahan, R. N. Pinckard

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

Platelet-activating factor is a novel phospholipid that has been implicated as an important mediator of acute allergic reactions. The intravenous administration of acetyl glyceryl ether phosphorylcholine, a pure, synthetic platelet-activating factor, causes electrocardiographic changes in the rabbit similar to those which are characteristic manifestations of systemic anaphylaxis. To determine whether platelet-activating factor contributes to anaphylactic cardiac dysfunction, we measured platelet-activating factor release from the sensitized guinea pig heart challenged in vitro with specific antigen and compared the resulting cardiac dysfunction with that induced by the injection of acetyl glyceryl ether phosphorylcholine into nonsensitized hearts. The results of these studies document that, during anaphylaxis in the isolated guinea pig heart, a platelet-activating factor is released into the coronary effluent that has physicochemical and functional properties similar to those of acetyl glyceryl ether phosphorylcholine. The intracardiac administration of acetyl glyceryl ether phosphorylcholine (10-14 to 3 x 10-9 mol) induced dose-related decreases in left ventricular contractile force (-5 to -85%) and coronary flow (-5 to -85%), as well as impaired atrioventricular conduction. The negative inotropic effect of acetyl glyceryl ether phosphorylcholine also was present in hearts perfused at constant flow. Although, in these hearts, acetyl glyceryl ether phosphorylcholine increased coronary resistance, which may have caused regional shunting and ischemia, it is unlikely that the negative inotropic effect of acetyl glyceryl ether phosphorylcholine was secondary to changes in coronary flow, since acetyl glyceryl ether phosphorylcholine also caused a dose-dependent negative inotropic effect in the electrically paced, noncoronary-perfused left atrium and right ventricular papillary muscle. Moreover, the cardiac effects of acetyl glyceryl ether phosphorylcholine were not modified by indomethacin or FPL 55712, indicating that they were not mediated by various cyclooxygenase or lipoxygenase products of the arachidonic acid cascade. These data suggest that platelet-activating factor may contribute to the contractile failure, reduced coronary flow, and conduction arrhythmias of cardiac anaphylaxis.

Original languageEnglish (US)
Pages (from-to)117-124
Number of pages8
JournalCirculation research
Volume54
Issue number2
DOIs
StatePublished - Jan 1 1984

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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