Margarita Rosa Romero-Imbachi1, Nelson Cupitra2, Karen Ángel3, Beatriz González4, Omar Estrada4, Juan C Calderón2, Jimmy Guerrero-Vargas3, José Beltrán3, Raul Narvaez-Sanchez5. 1. Physiology and Biochemistry Research Group-PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia; Herpetological and Toxinological Research Group, Faculty of Natural, Exact and Educational Sciences, University of Cauca, Popayán, Colombia. 2. Physiology and Biochemistry Research Group-PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia. 3. Herpetological and Toxinological Research Group, Faculty of Natural, Exact and Educational Sciences, University of Cauca, Popayán, Colombia. 4. Laboratory of Cellular Physiology, Center for Biophysics and Biochemistry, Venezuelan Institute for Scientific Research, Venezuela. 5. Physiology and Biochemistry Research Group-PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, Colombia. Electronic address: raul.narvaez@udea.edu.co.
Abstract
Centruroides margaritatus scorpion stings are common in Colombia. However, the cardiovascular toxicity of the venom has not been clarified. AIM: To study the effect and mechanisms of action of the complete venom of C. margaritatus (CmV) on the murine cardiovascular system. METHODS: We evaluated the in vivo effect of CmV LD50 on the mean arterial pressure (MABP), heart rate, and surface electrocardiogram in male adult normotensive Wistar rats. Ex vivo, we evaluated the vascular reactivity of rat aortic rings to increasing concentrations (1 to 60 μg/mL) of CmV using the blockers L-NAME, indomethacin, seratrodast, and prazosin. RESULTS: In the first hour of poisoning, CmV increased the MABP. In the second hour after poisoning, the heart rate decreased as the normalized PR interval and QT corrected increased. After that, cardiovascular shock was demonstrated by a drastic fall in the MABP and signs of cardiac conduction system block. In aortic rings, CmV caused a direct vasoconstrictor effect mediated by alpha-1 adrenergic receptors and counteracted by nitric oxide. CONCLUSION: The direct vascular and probably the cardiac alpha-1 effects likely explain the transient hypertension and the maintenance of cardiac function, while interval lengthening may be due to K+ channel blockage. Afterwards, the effects of both the alpha-1 pathway and the K+ channel pathway converged, resulting in fatal cardiovascular shock. This knowledge could aid in understanding the dynamics of the effects of the venom and in designing treatments to address its cardiovascular effects.
Centruroides margaritatus scorpion stings are common in Colombia. However, the cardiovascular toxicity of the venom has not been clarified. AIM: To study the effect and mechanisms of action of the complete venom of C. margaritatus (CmV) on the murine cardiovascular system. METHODS: We evaluated the in vivo effect of CmV LD50 on the mean arterial pressure (MABP), heart rate, and surface electrocardiogram in male adult normotensive Wistar rats. Ex vivo, we evaluated the vascular reactivity of rat aortic rings to increasing concentrations (1 to 60 μg/mL) of CmV using the blockers L-NAME, indomethacin, seratrodast, and prazosin. RESULTS: In the first hour of poisoning, CmV increased the MABP. In the second hour after poisoning, the heart rate decreased as the normalized PR interval and QT corrected increased. After that, cardiovascular shock was demonstrated by a drastic fall in the MABP and signs of cardiac conduction system block. In aortic rings, CmV caused a direct vasoconstrictor effect mediated by alpha-1 adrenergic receptors and counteracted by nitric oxide. CONCLUSION: The direct vascular and probably the cardiac alpha-1 effects likely explain the transient hypertension and the maintenance of cardiac function, while interval lengthening may be due to K+ channel blockage. Afterwards, the effects of both the alpha-1 pathway and the K+ channel pathway converged, resulting in fatal cardiovascular shock. This knowledge could aid in understanding the dynamics of the effects of the venom and in designing treatments to address its cardiovascular effects.