The influence of midazolam on heart rate arises from cardiac autonomic tones alterations in Burmese pythons, Python molurus

摘要

Abstract The GABA A receptor agonist midazolam is a compound widely used as a tranquilizer and sedative in mammals and reptiles. It is already known that this benzodiazepine produces small to intermediate heart rate (HR) alterations in mammals, however, its influence on reptiles' HR remains unexplored. Thus, the present study sought to verify the effects of midazolam on HR and cardiac modulation in the snake Python molurus . To do so, the snakes' HR, cardiac autonomic tones, and HR variability were evaluated during four different experimental stages. The first stage consisted on the data acquisition of animals under untreated conditions, in which were then administered atropine (2.5mgkg ?1 ; intraperitoneal), followed later by propranolol (3.5mgkg ?1 ; intraperitoneal) (cardiac double autonomic blockade). The second stage focused on the data acquisition of animals under midazolam effect (1.0mgkg ?1 ; intramuscular), which passed through the same autonomic blockade protocol of the first stage. The third and fourth stages consisted of the same protocol of stages one and two, respectively, with the exception that atropine and propranolol injections were reversed. By comparing the HR of animals that received midazolam (second and fourth stages) with those that did not (first and third stages), it could be observed that this benzodiazepine reduced the snakes' HR by ~60%. The calculated autonomic tones showed that such cardiac depression was elicited by an ~80% decrease in cardiac adrenergic tone and an ~620% increase in cardiac cholinergic tone – a finding that was further supported by the results of HR variability analysis. Graphical abstract Display Omitted Highlights ? A systemic administration of midazolam elicited bradycardia in Burmese pythons. ? Such bradycardia was mediated by the autonomic nervous system. ? Midazolam decreased cardiac adrenergic tone and increased cardiac cholinergic tone. ? Midazolam did not induce changes in the animals' intrinsic heart rate.