Rattlesnake venom shock in the rat: development of a method

Abstract

A model in Wistar rats (n = 30, 279-345 g) was developed to study circulatory, respiratory, metabolic, and lethal effects of an intravenous infusion (30 min; 1.25, 1.5, 1.75, and 2.0 mg/kg) of rattlesnake (Crotalus viridis helleri) venom. Venom produced perfusion failure with lactacidemia, hemoconcentration, hypoproteinemia, and death. The severity of poisoning was proportional to the quantity of venom given and to the elevation in lactic acid and hematocrit. Hemorrhages in the diaphragm, intercostal muscles, and intestine were observed at necropsy. In a separate test, rats (n = 12, 311-355 g) received an infusion of 1.5 mg/kg of venom or physiological salt solution. Blood volume was measured 30 min after the end of infusion in both groups with radioiodinated (125I) human serum albumin (RIHSA) and 51Cr-labeled rat red cells. Venom produced a significant reduction in total blood volume index (35%, P less than 0.001), plasma volume index (46%, P less than 0.001), and red cell mass indec (22% P less than 0.005). The slope of the RIHSA-disappearance curve of animals that received venom was more than twice that of the control group. We conclude that perfusion failure following rattlesnake envenomation is associated with hypovolemia due to increases in vascular permeabiltiy and hemorrhage.

Role of nitric oxide in the local and systemic pathophysiological effects induced by Bothrops asper snake venom in mice

“…After its synthesis in vascular endothelial cells, NO exerts cytoprotective effect and contributes to vascular homeostasis [49,50]. Hence, since systemic envenomation by crotaline snake venoms is associated with prominent hemodynamic disturbances [2,51], inhibition of eNOS by L-NAME may play a deleterious role by jeopardizing the constitutively local vascular production of NO by eNOS. The role of NO in ischemia is complex and multifactorial, since NO generated by iNOS present in infl ammatory cells exerts deleterious roles contributing to late-phase damage [52].…”

Preclinical Evaluation of the Efficacy of Antivenoms for Snakebite Envenoming: State-of-the-Art and Challenges Ahead

“…Examples are: (a) Cardiovascular alterations: Some studies have monitored the effects of venoms on the mean arterial blood pressure after i.v. injection of venoms [80,81]. Alternatively, the increments in the blood lactic acid concentration might be used to monitor the increment in anaerobic metabolism as a consequence of reduced blood flow and ischemia in tissues [80].…”

“…injection of venoms [80,81]. Alternatively, the increments in the blood lactic acid concentration might be used to monitor the increment in anaerobic metabolism as a consequence of reduced blood flow and ischemia in tissues [80]. (b) Thrombocytopenia and platelet hypoaggregation: Alterations in platelet counts and function are important in envenomings by some viperid species [82,83].…”

The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom: Pathophysiological mechanisms, prophylactic analgesia, and a surrogate in vitro assay

“…These observations strongly suggest that the cause of death in this experimental model is massive extravasation in the abdominal cavity and organs, generating a fulminant cardiovascular collapse within~20 min. These phenomena of hemoconcentration and hemorrhage, associated with increments in lactic acid secondary to ischemia, were previously described in a rat model of systemic envenoming by Crotalus atrox venom (Carlson et al, 1975). Systemic hemorrhage and plasma extravasation leading to cardiovascular shock are some of the main clinical manifestations in severe envenomings by B. asper and other viperid species (Warrell, 2004;Otero-Patiño, 2009).…”