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

The platelet-activating factor (PAF) antagonist BN-50739 can suppress certa in cardiac anhythmias. PAF is released from ischaemic myocardium and may co ntribute to initiation of ischaemia-induced ventricular fibrillation (VF). In this study we characterised the action of BN-50739 on left regional isch aemia-induced VF and examined whether effects are mediated within the ischa emic territory, or are nonspecific. In rat isolated Langendorff perfused he arts (n = 12/group), 10 mu M BN-50739 reduced the incidence of ischaemia-in duced 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 usi ng a dual-lumen tube that allows independent delivery of solution to the le ft and right coronary beds. Successful regional localisation of drug delive ry was confirmed by observing, before ischaemia, a regionally selective inc rease in coronary flow (p < 0.05), measured by using two in-line flow meter s. Protection against ischaemia-induced VF (p < 0.05) was achieved by pretr eatment with BN-50739, delivered selectively and entrapped within the invol ved region, but not when the drug was delivered to the uninvolved region. I n conclusion, BN-50739 protects against ischaemia-induced VF by eliciting a pharmacologic action in the involved (ischaemic) myocardium. This supports the hypothesis that BN-50739 suppresses an arrhythmogenic effect: of endog enous PAF released within the ischaemic tissue.