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 PLA2 inhibitor
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.