THE RELEASE OF LEUKOTRIENES AND THE VASCULAR CHANGES MEDIATED BY PLATELET-ACTIVATING-FACTOR AND CARDIAC ANAPHYLAXIS

The release of leukotrienes (LTs) as putative mediators of some of the cardiovascular changes that occurred during ovalbumin-induced cardiac anaphylaxis (CA) and following a bolus injection of platelet activati ng factor (PRF) was investigated, A bolus injection of PAF into the is olated perfused heart mimicked the effects of ovalbumin-induced cardia c anaphylactic reaction in sensitized heart characterised by a persist ent increase in coronary perfusion pressure (Cpp) and a protracted red uction in cardiac developed tension (Cdt). Quantitation of the heart p erfusate following bolus injections of ovalbumin or PAF showed the pre sence of significant amounts of LTs B-4, C-4, D-4 and E(4). Although t he total release of leukotrienes in response to PAF was significantly less than those released following ovalbumin challenge, leukotrienes C -4 and D-4 were the predominant LTs released for a duration of 8 min i n response to both of these stimuli, followed by LTE(4) and LTB(4), re spectively. The duration of LTB(4) release following ovalbumin challen ge was observed for more than 4 min whereas LTB(4) release following a bolus injection of PAF was observed for a duration of only 2 min. The challenged sensitized heart responded only once to ovalbumin challeng e. Even when exogenous arachidonic acid (AA) was infused prior to subs equent challenge with ovalbumin, the heart exhibited the same resistan ce to a second challenge and there was no subsequent increase in the o utput of LTs. The present data suggests that in both cardiac anaphylax is and PAF-induced cardiovascular changes LTs C-4 and D-4 are the main LTs released, followed by LTB(4) and LTE(4) and that enzymatic degrad ation of LTs which are independent of blood borne factors may occur in the isolated perfused heart. The failure in the induction of a second anaphylactic reaction in the same sensitized guinea-pig heart suggest s that depletion of AA is not one of the rate limiting steps that occu rred during cardiac anaphylactic reaction.