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

Abstract

The GABA 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; intraperitoneal), followed later by propranolol (3.5mgkg; intraperitoneal) (cardiac double autonomic blockade). The second stage focused on the data acquisition of animals under midazolam effect (1.0mgkg; 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.

The autonomic control of upright posture tachycardia in the arboreal lizard Iguana iguana

“…Thus, knowing that atropinized animals have only adrenergic and NANC mediation in their hearts, the decrease in P LF and the eradication of P HF induced by muscarinic cholinergic blockade, as shown by the PSA, reflect the fact that the LF f H oscillations are of sympathetic and parasympathetic origin, while the HF f H oscillations are only of parasympathetic origin (Figures a,d and a,d). This characteristic appears to be conserved among vertebrates (Akselrod et al., ; Braga et al., ; Carravieri, Müller, Yoda, Hayama, & Yamamoto, ; De Vera & González, ; Lopes, Armelin, Braga, & Florindo, ; Montano et al., ).…”

“…molurus (Serpentes; f H of ∼23 bpm) between 0.00 and 0.15 Hz (Lopes et al, 2017), that of Crocodylus porosus (Crocodylia; f H of ∼17 bpm) between 0.00 and 0.15 Hz (Seebacher & Franklin, 2004), that of Caiman latirostris (Crocodylia; f H of ∼18 bpm) between 0.00 and 0.15 Hz (Braga et al, 2016), and that of Ratus norvegicus (Mammalia; f H of ∼300 bpm) between 0.00 and 3.00 Hz (Kuwahara et al, 1994). This is probably a consequence of interspecific variations in the predominant mode of nervous cardio-regulation (sympathetic or parasympathetic) (Altimiras, 1999;Blasco, McKenzie, Taylor, & Rantin, 2017;Taylor et al, 2014;Teixeira, Armelin, Abe, Rantin, & Florindo, 2015), as well as of interspecific differences in basal f H -as animals with reduced f H naturally tend to exhibit less oscillations in this variable in a given period of time (resulting in spectra comprised within a range of lower frequencies).…”

Autonomic control of cardiovascular adjustments associated with orthostasis in the scansorial snakeBoa constrictor

“…Each snake was anaesthetised on a surgical table through inhalation of isoflurane (3%) and oxygen (97%) via a mask until it became unresponsive. The glottis was then intubated with silicone rubber for direct ventilation with isoflurane (1%) and oxygen (99%) at ∼2 breaths min −1 with a tidal volume of ∼18 ml kg −1 , manually maintained by a second experimenter using an anaesthesia gas blender coupled to a breathing balloon and a chronometer (Colibri Inhalatory Anaesthesia Apparatus, Brasmed Veterinary Products, Paulínia, SP, Brazil) (Mosley, 2005;Armelin et al, 2014;Lopes et al, 2017).…”

Echocardiography Evaluation of the Effects of Midazolam on Passive Leg Raising Test in Critically ill Patients in the Intensive Care Unit, diagnosed with Sepsis, determined to be hypovolemic and responding to fluid treatment

“…(16,42) In one study, systemic administration of the GABA A agonist midazolam to Python molorus caused signi cant bradycardia, while the direct cardiac effect of midazolam was not demonstrated; this effect was attributed to midazolam-mediated reduction of cardiac adrenergic tone and enhancement of cholinergic tone. (51) The mean arterial serum concentration of midazolam following intravenous induction (0.2 mg/kg) is 1.36 pg/mL in patients with ischemic heart disease. (18) This is a 95% su cient dose for unconsciousness.…”