INTERACTIONS OF PHOSPHOLIPID-DERIVED MEDIATORS IN CARDIAC ANAPHYLAXIS

A study was carried out to elucidate the interactions and significance of vasoactive phospholipid-derived mediators in cardiac anaphylaxis ( CA). Bolus intra-coronary injection of ovalbumin (OA) into actively se nsitized guinea-pig heart resulted in a profound reaction characterise d by a persistent triphasic increase in coronary perfusion pressure (C pp) and marked impairment of cardiac developed tension (Cdt). Immunore active (ir) leukotriene C-4 (LTC(4)), ir-prostaglandins (PGs) and ir-t hromboxane B-2 (TxB(2)), were detected in coronary effluent of heart u ndergoing CA. 5-lipoxygenase (5-LO) and cycloxygenase (CO) inhibitors, CGS 8515 and indomethacin markedly attenuated the early phase while p latelet activating factor (PAF) antagonist, WEB 2086 markedly attenuat ed the late phase of the anaphylactic increase in Cpp. Bolus injection of PAF and LTC(4) into non-sensitized isolated guinea-pig heart exhib ited responses which mimic many of the features of CA induced by OA. L TC(4) triggered release of ir-TxB(2) and ir-6-keto-PGF(1 alpha), whils t bolus injection of PAF induced release of ir-TxB(2) and ir-LTC(4). T he results of the present experiments suggests that the activity of di fferent vasoactive mediators predominates at different time points dur ing the course of anaphylactic reactions. This is further reflected by the fact that different stages of CA were modified by the use of resp ective PAF-antagonists, 5-LO and CO inhibitors and combination of use of these drugs markedly inhibited CA reaction. Thus, TxA(2) plays a pr edominant role at 1 to 2 min, LTs at 2 to 5 min and PAF is important a t a later stage (after 5 min) following the occurence of CA.