title: Contribution of platelets and platelet-activating factor (PAF) to the arrhythmogenic, haemodynamic and necrotic effects of acute myocardial ischaemia.
abstract: The effects of alterations in platelet activity on arrhythmias, haemodynamics and extent of necrosis during coronary ligation for 30 min were assessed in rabbits. Reduction of platelet counts to less than 1% of control by intravenous injection of platelet antiserum (1 ml kg-1 i.v.) reduced the volume of necrosed tissue from 23 +/- 2% to 15 +/- 1%, P less than 0.01 (expressed as % of total LV) and attenuated the hypotensive effect of ischaemia. Pretreatment with the platelet activating factor (PAF) antagonist BN 52021 also attenuated the hypotension and necrosis caused by coronary ligation 23 +/- 2% vs 14 +/- 1%, P less than 0.01. Pretreatment with the thromboxane antagonist CGS 13080 attenuated the hypotensive response to ischaemia but had only a very small effect on the area of necrosis. Administration of PAF at 10 min following coronary ligation markedly increased the volume of necrosed tissue 36 +/- 2%, P less than 0.01 and caused VF and haemodynamic collapse in 10 out of 12 animals. Pretreatment with platelet antiserum or the PAF antagonist BN 52021 reversed this effect of PAF. Pretreatment with CGS 13080 attenuated the marked hypotensive effect of PAF but failed to reverse its necrotic or arrhythmogenic effects. These findings indicate that platelet activation contributes to the necrosis and hypotension following coronary ligation and that platelet-activating factor may contribute to this. The ameliorating effects of platelet antiserum or BN 52021 support the concept that inhibition of platelet activity may have a useful role in the treatment of acute myocardial infarction.
authors.affiliation: Academic Cardiology Unit, St Mary's Hospital Medical School, London, U.K.
authors.forename: S
authors.initials: S
authors.lastname: Chakrabarty
authors.forename: P
authors.initials: P
authors.lastname: Thomas
authors.forename: D J
authors.initials: DJ
authors.lastname: Sheridan
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D001792:Blood Platelets / Q000187:drug effects*; D004224:Diterpenes; D046934:Ginkgolides; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D007106:Immune Sera / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D009336:Necrosis / Q000209:etiology / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D015539:Platelet Activation / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D004224:Diterpenes; D046934:Ginkgolides; D007093:Imidazoles; D007106:Immune Sera; D007783:Lactones; D010972:Platelet Activating Factor; D011725:Pyridines; D013928:Thromboxane A2; C037787:pirmagrel; C045856:ginkgolide B; D013930:Thromboxane-A Synthase