Abstract
We have investigated the ability of 5-hydroxytryptamine (5-HT) to elicit arrhythmic contractions in isolated human atrial strips as a function of pacing rate (0.1–2 Hz) using a method recently introduced by us (Kaumann and Sanders, this journal, 1993b) and examined the nature of the 5-HT receptors involved. Right atrial appendage tissue was obtained from 14 patients undergoing cardiac surgery. None of the patients had advanced heart failure. 5-HT (0.6–20 μmol/l) induced arrhythmic contractions during pacing in 4/11 atrial strips from 3/4 patients who had not received β blockers and in 21/27 atrial strips from 9/10 patients who had been chronically treated with β blockers (primarily β1-selective). The incidence of arrhythmic contractions evoked by 5-HT did not reach statistical significance in the atrial tissue from the non-β blocked patients but was highly significant in the atrial tissue from the chronically β blocked patients. The arrhythmic contractions usually occurred more frequently at low than at high pacing rates and were observed at the physiological frequency of 1 Hz in 1/4 atrial strips from 1/4 of the non-β blocked patients and 6/11 strips from 5/10 of the β blocked patients. The 5-HT-evoked arrhythmic contractions were observed during blockade of β1-adrenoceptors, β2-adrenoceptors and 5-HT3 receptors, ruling out the participation of these receptors. The 5-HT-evoked arrhythmic contractions were totally inhibited within 30 min by the selective 5-HT4 receptor antagonist SB 203186 ((1-piperidinyl)ethyl 1H-indole 3-carboxylate) 100 nmol/l whereas they persisted in time-matched controls. The blockade of 5-HT-evoked arrhythmic contractions by SB 203186 was surmounted by high concentrations (400–1800 μmol/l) of 5-HT. Our results demonstrate that 5-HT elicits rate-dependent arrhythmic contractions in isolated human atrium through the 5-HT4 receptor and that they are facilitated in atrial tissue from patients treated with β blockers. Our results suggest that endogenous, platelet-derived 5-HT may cause atrial arrhythmias and that exogenous 5-HT4 agonists/partial agonists may be arrhythmogenic.
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Correspondence to: A. J. Kaumann at the above address
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Kaumann, A.J., Sanders, L. 5-Hydroxytryptamine causes rate-dependent arrhythmias through 5-HT4 receptors in human atrium: facilitation by chronic β-adrenoceptor blockade. Naunyn-Schmiedeberg’s Arch Pharmacol 349, 331–337 (1994). https://doi.org/10.1007/BF00170877
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DOI: https://doi.org/10.1007/BF00170877