Catecholamines are key modulators of ventricular repolarization patterns in the ball python (Python regius)

Abstract

Ectothermic vertebrates experience daily changes in body temperature, and anecdotal observations suggest these changes affect ventricular repolarization such that the T-wave in the ECG changes polarity. Mammals, in contrast, can maintain stable body temperatures, and their ventricular repolarization is strongly modulated by changes in heart rate and by sympathetic nervous system activity. The aim of this study was to assess the role of body temperature, heart rate, and circulating catecholamines on local repolarization gradients in the ectothermic ball python (Python regius). We recorded body-surface electrocardiograms and performed open-chest high-resolution epicardial mapping while increasing body temperature in five pythons, in all of which there was a change in T-wave polarity. However, the vector of repolarization differed between individuals, and only a subset of leads revealed T-wave polarity change. RNA sequencing revealed regional differences related to adrenergic signaling. In one denervated and Ringer’s solution–perfused heart, heating and elevated heart rates did not induce change in T-wave polarity, whereas noradrenaline did. Accordingly, electrocardiograms in eight awake pythons receiving intra-arterial infusion of the β-adrenergic receptor agonists adrenaline and isoproterenol revealed T-wave inversion in most individuals. Conversely, blocking the β-adrenergic receptors using propranolol prevented T-wave change during heating. Our findings indicate that changes in ventricular repolarization in ball pythons are caused by increased tone of the sympathetic nervous system, not by changes in temperature. Therefore, ventricular repolarization in both pythons and mammals is modulated by evolutionary conserved mechanisms involving catecholaminergic stimulation.

Why are you talking with snakes? To get new evolutionary insights in cardiac electrophysiology!

“…During this era of translational research, it is refreshing to have a study featured in an earlier issue of JGP investigating cardiac electrophysiology in snakes ( Boukens et al, 2022 ). In Antoine de Saint-Exupéry’s book The Little Prince , first published in New York City during the Second World War, there are two mentions of snakes.…”

“…At the end of book, the narrator asks the Little Prince: “Why are you talking with snakes?” The reason is that the snake is admirably confident that he has mastered life’s mysteries ( de Saint-Exupéry, 1943 ). The study by Boukens et al (2022) in ball pythons is therefore important in several aspects: first, they provide an advance of scientific knowledge. From an evolutionary point of view, reptiles and mammals share a common ancestor in Amniote, with divergence occurring ∼315 million yr ago ( Warren et al, 2008 ).…”

Catecholamines help snakes have a change of heart

“…In mammals, ventricular repolarization is regulated by catecholamines released by the autonomic nervous system. In this issue of JGP , Boukens et al show that this mode of regulation is conserved in the ball python, Python regius ( 1 ).…”

“…The researchers therefore recorded ECGs in living ball pythons as their body temperatures were increased ( 1 ). The ball python’s heart is unique in having functionally distinct ventricles, with a high-pressure left side and a low-pressure right side, even though, as in other snakes, the two sides are not anatomically separated.…”

“…In 1880, Burdon-Sanderson and Page ( 5 ) showed in their classic experiments that local differences in temperature change T-wave polarity in the ectothermic heart, presumably due to a direct effect of temperature on the activity of cardiac ion channels. However, when Boukens et al recorded an ECG from a decapitated python, they found that raising temperature did not cause T-wave inversion ( 1 ). “So, we realized that it might not be a direct effect of temperature but might involve another factor, namely catecholamines released by the autonomic nervous system,” says Boukens.…”