title: Protective effect of a specific platelet-activating factor antagonist, BN 52021, on bupivacaine-induced cardiovascular impairments in rats.
abstract: Administration of the local anaesthetic bupivacaine (1.5 or 2 mg/kg, i.v.) to rats elicited a marked decrease of mean arterial blood pressure (MBP) and heart rate (HR) leading to death (in 67% or 90% of animals respectively). Intravenous injection of the specific platelet-activating factor (PAF) antagonist BN 52021 (10 mg/kg), 30 min before bupivacaine administration (2 mg/kg i.v.) suppressed both the decrease of MBP and HR. In contrast, doses of 1 mg/kg BN 52021 given 30 min before or 10 mg/kg administered 5 min before i.v. injection of bupivacaine were ineffective. When BN 52021 (20 mg/kg i.v.) was injected immediately after bupivacaine (2 mg/kg), a partial reversion of the decrease of MBP and HR was observed, whereas the dose of 10 mg/kg was ineffective. A partial recovery of bupivacaine-induced ECG alterations was observed after pretreatment of the rats with BN 52021. Since the administration of BN 52021, at all doses studied, did not alter MBP and HR at the doses used, the bulk of these results clearly demonstrate a protective action of BN 52021, a specific antagonist of PAF, against bupivacaine-induced cardiovascular toxicity. Thus, consistent with its direct effect on heart, PAF appears to be implicated in bupivacaine-induced cardiovascular alterations.
authors.affiliation: Department of Pharmacology, University of Sao Paulo, Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Lagente
authors.forename: M P
authors.initials: MP
authors.lastname: Simonetti
authors.forename: Z B
authors.initials: ZB
authors.lastname: Fortes
authors.forename: P
authors.initials: P
authors.lastname: Braquet
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D004224:Diterpenes; D004562:Electrocardiography; D046934:Ginkgolides; D006339:Heart Rate / Q000187:drug effects; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B; D002045:Bupivacaine