4.6 EFECTO DEL AZUL DE METILENO EN LA HIPOTENSIÓN Y BRADICARDIA ASOCIADO A LA ADMINISTRACIÓN DE UNA DOSIS LETAL DE VENENO TOTAL DE CASCABEL VENEZOLANA (CROTALUS DURISSUS CUMANENSIS) EN RATAS.

Abstract

The effects of pre treatment with methylene blue (MB) on the cardiovascular effect caused by the administration of total venom (TV) of Crotalus durissus cumanensis was studied in adult rats, allocated into two groups: group I, six rats treated with TV (single dose: 1.5 mg/kg, IV) and group II, six rats treated with a 2% solution of MB (single dose: 2 mg/kg, IV) and forty min later, TV was injected as in group I. Before the onset of the experiments, each rat was anesthetized with azaperone:ketamine. The femoral artery and vein were cannulated to record blood pressure (mean arterial pressure: MAP) and to infuse solutions respectively. Heart rate (HR) was estimated by electrocardiography. MAP and HR were measured before and after the treatments (5, 10, 20 and 30 min). Differences between treatments were estimated by repeated measures ANOVA. A sudden (5min) reduction in MAP (from 87.0  8.4 to 31.8  3.6mmHg) and HR (from 260.0  12.7 to 170.0  10.0 lat/min) was observed in group I. This reduction was steadily during the first 10 min, followed by death in all treated rats. Rats in group II did not exhibit significant (P>0.05) changes in MAP and HR after the administration of MB. Forty min later, TV was injected causing a reduction in MAP (73.0  6.6 to 27.0  2.8mmHg) and HR (360.0  9.9 to 180.0  9.0 l/min). After 10 min, the MAP and HR returned to baseline levels, reaching 72.6  7.9mmHg and 360.0  11.0 lat/min, respectively, with a 100% survival at 24h. MB inhibits soluble guanylate cyclase, the cellular target of nitric oxide (NO). Therefore, the possibility exists that this venom might activate the production and release of NO, contributing to the observed hypotension and bradycardia. Since MB restored these haemodynamic variables and avoided the venom-evoked death at 24 hours, it might be a potential useful therapeutic tool to control the shock caused by this total venom.