Possible involvement of platelet activating factor in anaphylaxis of passively sensitised, isolated guinea pig hearts.
There is evidence that cardiac tissue may be a target for antigen/antibody reactions. Platelet activating factor (PAF) is released during anaphylaxis and could mediate cardiac damage. To investigate this, guinea pigs were passively sensitised by anti-ovalbumin rabbit serum (6 mg.kg-1 intravenously) and 24 h later their hearts were excised and isolated according to a working heart preparation technique. After a 20 min equilibration period, anaphylactic challenge was induced by a bolus injection of ovalbumin (2 mg in 0.2 ml buffer) via the side arm of the aortic cannula. Heart rate, coronary flow, aortic flow, left ventricular developed pressure (LVDP), its first derivative (LVdp/dtmax) and left ventricular end diastolic pressure (LVEDP) were recorded. After ovalbumin challenge, heart rate and LVEDP were markedly increased, while coronary flow, aortic flow, LVDP, and LVdp/dtmax were profoundly decreased. All these alterations were over within 5 min, and the measured variables returned to approximately the pre-challenge values. BN 52021, a specific PAF receptor antagonist, was dissolved in the perfusion buffer and given in doses of 15, 30 and 60 mumol.litre-1 10 min prior to the induction of anaphylactic challenge until the end of the observation period. BN 52021 inhibited the increase in heart rate and LVEDP and the decrease in coronary and aortic flow, LVDP and LVdp/dtmax in a dose dependent manner. The changes produced by 30 and 60 mumol.litre-1 were statistically significant at the levels of p less than 0.01 and p less than 0.001 when compared to the control values.(ABSTRACT TRUNCATED AT 250 WORDS)
Tosaki
A
A
Institute Henri Beaufour, Le Plessis Robinson, France.
Koltai
M
M
Braquet
P
P
Szekeres
L
L
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D007116:Immunization, Passive; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C045856:ginkgolide B