title: Hemodynamic responses to Lachesis muta (South American bushmaster) snake venom in anesthetized rats.
abstract: In this work, we examined the hemodynamic responses to Lachesis muta (South American bushmaster) venom in anesthetized male Wistar rats. Venom (1.5 mg/kg, i.v.) caused immediate hypotension that was followed by a gradual return towards baseline over 60 min; there were no significant changes in heart rate, ECG parameters and respiratory rate. A higher dose (3 mg/kg, i.v.) caused sustained hypotension, variable bradycardia, respiratory depression and fluctuations in ECG; death occurred within 10-60 min. Venom injected intramuscularly (15 mg/kg) produced a smaller decrease in blood pressure that was more persistent than with 1.5 mg/kg (i.v.). Pre-treatment with atenolol (selective β1-adrenergic receptor antagonist) potentiated the response to venom (1.5 mg/kg, i.v.) and resulted in a hemodynamic profile similar to that seen with 3 mg/kg (i.v.). Macroscopically, systemic hemorrhage was seen only in the ileum, whereas histological analysis revealed extensive pulmonary hemorrhage; the heart, liver and kidney were generally unaffected. Intravascular pulmonary thrombosis occurred with venom given i.v. and i.m., but was less marked with the latter route. In rat isolated perfused hearts, venom caused a persistent decrease in left ventricular developed pressure but no change in heart rate, coronary flow or ECG; there was tissue necrosis and release of CK-MB that were abolished by pre-treating venom with the PLA2inhibitor p-bromophenacyl bromide. These results show that in rats L. muta venom causes hypotension, bradycardia and respiratory depression, depending on the dose and route of administration. The hemodynamic responses apparently do not involve direct cardiotoxicity and are modulated by the adrenergic system.
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Dias
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
authors.forename: Mariana A P
authors.initials: MA
authors.lastname: Rodrigues
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
authors.forename: André L
authors.initials: AL
authors.lastname: Rennó
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stroka
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
authors.forename: Bruna R
authors.initials: BR
authors.lastname: Inoue
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
authors.forename: Patrícia C
authors.initials: PC
authors.lastname: Panunto
authors.affiliation: Setor de Biologia, Divisão de Zoologia Médica, Instituto Vital Brazil, Niterói, RJ, Brazil.
authors.forename: Anibal R
authors.initials: AR
authors.lastname: Melgarejo
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil. Electronic address: hyslop@fcm.unicamp.br.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hyslop
mesh_terms: D000818:Animals; D001919:Bradycardia / Q000139:chemically induced; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D009206:Myocardium / Q000473:pathology; D017208:Rats, Wistar; D056152:Respiratory Rate / Q000187:drug effects; D012909:Snake Bites / Q000473:pathology / Q000503:physiopathology*; D014757:Viper Venoms / Q000633:toxicity*; D017819:Viperidae
chemical_list: D014757:Viper Venoms
keywords: Bradycardia; Cholinergic neurotransmission; Hemorrhage; Hypotension; Lachesis muta venom; Pulmonary thrombosis; β(1)-adrenergic receptors