Hemodynamic responses to Lachesis muta (South American bushmaster) snake venom in anesthetized rats
Hemodynamic responses to Lachesis muta (South American bushmaster) snake venom in anesthetized rats
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DOI：
10.1016/j.toxicon.2016.10.001
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发表时间：
2016-12-01
期刊：
影响因子：
2.8
通讯作者：
Hyslop, Stephen
中科院分区：
文献类型：
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作者：
Dias, Lourdes;Rodrigues, Mariana A. P.;Hyslop, Stephen
在这项工作中，我们研究了麻醉雄性Wistar大鼠对南美毒蛇毒液的血液动力学反应。毒液（1.5 mg/kg，静脉注射）引起立即低血压，随后在60分钟内逐渐恢复到基线水平；心率、心电参数及呼吸频率无明显变化。较高剂量（3mg /kg，静脉注射）引起持续低血压、变异性心动过缓、呼吸抑制和心电图波动；死亡发生在10-60分钟内。肌肉注射毒液（15mg /kg）产生的血压下降较小，且比1.5 mg/kg（静脉注射）更持久。阿替洛尔（选择性β(1)-肾上腺素能受体拮抗剂）预处理增强了对毒液（1.5 mg/kg，静脉注射）的反应，并导致与3mg /kg（静脉注射）相似的血流动力学特征。宏观上，全身性出血仅见于回肠，而组织学分析显示广泛的肺出血；心脏、肝脏和肾脏一般未受影响。静脉注射和静脉注射毒液均可发生血管内肺血栓形成，但后一种途径的血栓形成较少。在大鼠离体灌注心脏中，毒液引起左心室发育压持续下降，但心率、冠状动脉血流或心电图无变化；用PLA(2)抑制剂对溴苯酰溴预处理毒液可消除组织坏死和CK-MB的释放。这些结果表明，大鼠变形蛇毒液引起低血压、心动过缓和呼吸抑制，这取决于剂量和给药途径。血流动力学反应显然不涉及直接的心脏毒性，而是由肾上腺素能系统调节的。(C) 2016 Elsevier Ltd.版权所有。
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 beta(1)-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 PLA(2) 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. (C) 2016 Elsevier Ltd. All rights reserved.