Contractile effects of dexmedetomidine in the human heart

TL;DR

This study shows that dexmedetomidine, a sedative drug, can affect heart muscle contractions through histamine and adrenergic pathways.

Contribution

The study reveals a new direct cardiac effect of dexmedetomidine via H2-histamine receptors and endogenous catecholamine release.

Findings

Dexmedetomidine increases heart contraction force in human atrial tissue.

Its effects are modulated by histamine receptor agonists and β-adrenergic antagonists.

Dexmedetomidine acts as a partial H2-histamine receptor agonist and releases endogenous β-adrenergic catecholamines.

Abstract

Dexmedetomidine is an approved drug that is chemically related to clonidine. Dexmedetomidine is used to induce sedation and anxiolysis. These therapeutic effects of dexmedetomidine are explained by its agonistic action on brain α2-adrenoceptors. We tested the hypothesis that dexmedetomidine like clonidine also stimulated human cardiac atrial H2-histamine-receptors. We noted that 10 µM dexmedetomidine increased force of contraction in electrically stimulated (1 Hz) human right atrial preparations (HAP, obtained during open heart surgery). These effects were increased by previously applied cilostamide and slightly attenuated by subsequently applied 10 µM cimetidine but greatly attenuated by 10 µM propranolol or when first 10 µM cocaine was given. After pre-stimulation with histamine, subsequently applied 1 µM dexmedetomidine reduced force of contraction in HAP. In left atrial preparations from mice with cardiac-specific overexpression of H2-histamine receptors (H2-TG), we noted a positive inotropic effect of 10 µM dexmedetomidine in the presence of 100 nM rolipram that was reversed by cimetidine. In left atrial preparations of wild-type mice, 10 µM dexmedetomidine increased force of contraction in the presence of rolipram which was reversed by subsequently applied 10 µM propranolol and attenuated by pretreatment with 10 µM cocaine. These data indicate a direct cardiac action of dexmedetomidine. Dexmedetomidine can probably, in principle, release endogenous cardiac noradrenaline. Thus, dexmedetomidine can act as a partial agonist at human cardiac H2-histamine receptors but its main effect in HAP is the release of endogenous β-adrenergic catecholamines.

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