title: Modulation of antigen- and ischemia-induced effects by the platelet-activating factor antagonist WEB-2086 in isolated sensitized rat hearts.
abstract: The modulatory role of the platelet-activating factor (PAF) antagonist WEB-2086 (30 microM) on the response to antigen-induced (trinitrophenyl-haptenized ovalbumin) and global ischemia (30 and 60 min)-induced changes in the response to antigen was studied in isolated hearts from actively sensitized rats. In sensitized normoxic hearts, both antigen (0.8 mg) and PAF (100 pmol) induced a short-term increase followed by a long-term decrease in coronary flow (CF). The antigen- but not the PAF-evoked increase in CF was accompanied by a substantial release of histamine. WEB-2086 enhanced the vasodilator effect and abolished the vasoconstrictor effect of 100 pmol of PAF but neither modified the coronary vascular effects of antigen nor the antigen-induced histamine release. Ischemia for 60 min followed by 30 min of reperfusion increased the diastolic left ventricular pressure but a 30-min period of ischemia and reperfusion had no effect on baseline cardiac function. WEB-2086 had no effect on ischemia-induced changes in cardiac function. A 30-min period of global ischemia enhanced the antigen-induced decrease in CF and systolic left ventricular pressure (SLVP). A 60 min period, however, suppressed the antigen-induced effects on CF and SLVP as well as antigen-induced histamine release. WEB-2086 partly protected the heart against the enhanced antigen-induced decrease in CF and SLVP after a 30-min period of global ischemia but no modulatory role of WEB-2086 was observed after 60 min of global ischemia. Our conclusions are that (a) PAF is not involved in rat cardiac anaphylaxis since WEB-2086 was proven to be inactive; (b) cardiac ischemia and cardiac anaphylaxis have interrelated mechanism of action since ischemia changed the anaphylactic response, which indicates that coincidence of these two pathological events could influence the clinical outcome; and (c) PAF is possibly involved in rat cardiac ischemia since WEB-2086 partly protected the heart against the enhanced antigen-induced decrease in CF and SLVP after 30 min of ischemia and reperfusion.
mesh_terms: D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D000941:Antigens; D001381:Azepines / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002867:Chromones / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006636:Histamine Release; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000941:Antigens; D001381:Azepines; D002867:Chromones; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; C006312:FPL 55712