Protection against ventricular fibrillation by the PAF antagonist, BN-50739, involves an ischaemia-selective mechanism

Journal of Cardiovascular Pharmacology
K E Baker, M J Curtis

Abstract

The platelet-activating factor (PAF) antagonist BN-50739 can suppress certain cardiac arrhythmias. PAF is released from ischaemic myocardium and may contribute to initiation of ischaemia-induced ventricular fibrillation (VF). In this study we characterised the action of BN-50739 on left regional ischaemia-induced VF and examined whether effects are mediated within the ischaemic territory, or are nonspecific. In rat isolated Langendorff perfused hearts (n = 12/group), 10 microM BN-50739 reduced the incidence of ischaemia-induced VF from 75 to 17% (p<0.05). This was accompanied by QT widening and an increase in coronary flow. Heart rate and PR interval were not affected by the drug. In separate studies, isolated rat hearts were perfused by using a dual-lumen tube that allows independent delivery of solution to the left and right coronary beds. Successful regional localisation of drug delivery was confirmed by observing, before ischaemia, a regionally selective increase in coronary flow (p<0.05), measured by using two in-line flow meters. Protection against ischaemia-induced VF (p<0.05) was achieved by pretreatment with BN-50739, delivered selectively and entrapped within the involved region, but not when the drug was delivered to...Continue Reading

Citations

Mar 1, 1992·Circulation·S W Ely, R M Berne
May 1, 1992·Circulation Research·S YamanakaK Yamamoto
Apr 1, 1987·Journal of Molecular and Cellular Cardiology·M J CurtisM J Walker
Sep 1, 1983·British Journal of Pharmacology·J BenvenisteC Labat
May 1, 1993·Cardiovascular Research·M J CurtisM J Walker
Jun 15, 1993·The Biochemical Journal·W Chao, M S Olson
Dec 7, 1995·Biochimica Et Biophysica Acta·T Izumi, T Shimizu
Oct 1, 1995·Journal of Cardiovascular Electrophysiology·M R Rosen
Feb 1, 1996·Inflammation·M KöllerW König

Related Concepts

Establishment and Maintenance of Localization
Ischemia
Ventricular Fibrillation
Entire Lumen of Body System
Antagonist Muscle Action
Perfusion
Transcription Initiation
Myocardium
Triazoles
Myocardial Stunning

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