Gaspar Matheus Z, Yabunaka Ana C, Silva-Carvalho Rosimeire, Nascimento Charles U, Brinholi Rejane B, Silva Elisangela O, Gerez Juliana R, Silva Nelson J, Torres-Bonilla Kristian A, Hyslop Stephen, Pacagnelli Francis L, Floriano Rafael S
Laboratory of Toxinology and Cardiovascular Research, Graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Rodovia Raposo Tavares Km 572, Presidente Prudente, SP, 19067-175, Brazil.
Laboratory of Cardiac Structural and Functional Assessment, Graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Rodovia Raposo Tavares Km 572, Presidente Prudente, SP, 19067-175, Brazil.
Cardiovasc Toxicol. 2023 Apr;23(3-4):132-146. doi: 10.1007/s12012-023-09786-6. Epub 2023 Feb 22.
In this work, we examined the action of two South American coralsnake (Micrurus corallinus and Micrurus dumerilii carinicauda) venoms on rat heart function in the absence and presence of treatment with Brazilian coralsnake antivenom (CAV) and varespladib (VPL), a potent phospholipase A inhibitor. Anesthetized male Wistar rats were injected with saline (control) or a single dose of venom (1.5 mg/kg, i.m.) and monitored for alterations in echocardiographic parameters, serum CK-MB levels and cardiac histomorphology, the latter using a combination of fractal dimension and histopathological methods. Neither of the venoms caused cardiac functional alterations 2 h after venom injection; however, M. corallinus venom caused tachycardia 2 h after venom injection, with CAV (given i.p. at an antivenom:venom ratio of 1:1.5, v/w), VPL (0.5 mg/kg, i.p.) and CAV + VPL preventing this increase. Both venoms increased the cardiac lesional score and serum CK-MB levels compared to saline-treated rats, but only the combination of CAV + VPL prevented these alterations, although VPL alone was able to attenuate the increase in CK-MB caused by M. corallinus venom. Micrurus corallinus venom increased the heart fractal dimension measurement, but none of the treatments prevented this alteration. In conclusion, M. corallinus and M. d. carinicauda venoms caused no major cardiac functional alterations at the dose tested, although M. corallinus venom caused transient tachycardia. Both venoms caused some cardiac morphological damage, as indicated by histomorphological analyses and the increase in circulating CK-MB levels. These alterations were consistently attenuated by a combination of CAV and VPL.
在本研究中，我们考察了两种南美珊瑚蛇（珊瑚眼镜蛇和杜氏珊瑚蛇指名亚种）毒液在未治疗以及用巴西珊瑚蛇抗蛇毒血清（CAV）和伐瑞拉地（VPL，一种有效的磷脂酶A抑制剂）治疗情况下对大鼠心脏功能的作用。将麻醉的雄性Wistar大鼠注射生理盐水（对照）或单剂量毒液（1.5 mg/kg，肌肉注射），并监测超声心动图参数、血清肌酸激酶同工酶MB（CK-MB）水平和心脏组织形态学的变化，后者采用分形维数和组织病理学方法相结合的方式进行检测。毒液注射后2小时，两种毒液均未引起心脏功能改变；然而，珊瑚眼镜蛇毒液在注射后2小时引起心动过速，而CAV（以抗蛇毒血清与毒液1:1.5的比例腹腔注射，v/w）、VPL（0.5 mg/kg，腹腔注射）以及CAV + VPL可防止这种增加。与生理盐水处理的大鼠相比，两种毒液均增加了心脏损伤评分和血清CK-MB水平，但只有CAV + VPL的组合可防止这些改变，尽管单独使用VPL能够减弱珊瑚眼镜蛇毒液引起的CK-MB升高。珊瑚眼镜蛇毒液增加了心脏分形维数测量值，但没有一种治疗方法能防止这种改变。总之，在测试剂量下，珊瑚眼镜蛇和杜氏珊瑚蛇指名亚种毒液未引起主要的心脏功能改变，尽管珊瑚眼镜蛇毒液引起了短暂的心动过速。组织形态学分析和循环CK-MB水平升高表明，两种毒液均造成了一些心脏形态损伤。CAV和VPL的组合持续减弱了这些改变。
