The proarrhythmic effects of hypothermia in atria isolated from 5-HT4-receptor-overexpressing mice.

Abstract

We investigated whether hypothermia would be arrhythmogenic in mice that overexpress the human 5-HT4 receptor only in their cardiac myocytes (5-HT4-TG). Contractile studies were performed in isolated, electrically driven (1 Hz) left and spontaneously beating right atrial preparations of 5-HT4-TG and littermate wild-type control mice (WT). Hypothermia (23 °C) decreased the force of contraction in the mouse right and left atrial preparations. Moreover, the concentration-dependent positive inotropic effects of 5-HT were blunted but still shifted to lower 5-HT concentrations in the left 5-HT4-TG atria in hypothermia compared to normothermia (37 °C). Furthermore, hypothermia increased the incidence of right atrial arrhythmias in 5-HT4-TG more than in WT mice. In contrast, at 37 °C, lowering the potassium concentration from 5.2 to 2.0 mM also induced arrhythmias in the right atrium, but with a similar incidence in WT and 5-HT4-TG mice. In contrast, 10 μM d,l-sotalol and 300 μM erythromycin did not induce arrhythmias. Hypothermia was accompanied by the increased expression of heat shock protein 70 (HSP70) in WT but not in 5-HT4-TG mice. We concluded that without the stimulation of 5-HT4-receptors by exogenous agonists, a simple temperature reduction can increase arrhythmias in 5-HT4-TG mice. It is tempting to speculate that in human patients, 5-HT4 receptors might contribute to potentially deadly hypothermia-induced arrhythmias.

• Authors: Ulrich Gergs, Tobias Brückner, Britt Hofmann, Joachim Neumann
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 906 Pg. 174206 (Sep 05 2021) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 34048737 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Receptors, Serotonin, 5-HT4

Topics

• Animals
• Arrhythmias, Cardiac (etiology, physiopathology)
• Atrial Function (physiology)
• Disease Models, Animal
• Humans
• Hypothermia (complications)
• Isolated Heart Preparation
• Mice
• Mice, Transgenic
• Myocardial Contraction (physiology)
• Myocytes, Cardiac (metabolism)
• Receptors, Serotonin, 5-HT4 (genetics, metabolism)