Long term treatment with β-adrenoceptor antagonists (β-blockers) has been associated with an enhanced 5-HT-induced increase in human atrial contractility (Sanders et al. 1995). However, the influence of chronic β-blockade on the human atrial cellular electrophysiological response to 5-HT has not yet been studied. We aimed to investigate the effect of 5-HT on action potentials and refractoriness in patients treated and not treated with β-blockers.
The whole cell perforated patch clamp technique was used to record electrical activity from cells isolated enzymatically from the right atrial appendage of consenting patients undergoing cardiac surgery (Workman et al. 2001). Procedures for obtaining tissues were approved by the institutional ethics committee, and conform to the Declaration of Helsinki. All patients were in sinus rhythm at the time of surgery.
The heart rate was significantly higher in patients not treated with β-blockers, at 78 ± 3 beats per minute (bpm) (mean ± S.E.M.) than in patients treated with β-blockers, at 63 ± 4 bpm (P < 0.05; Student’s unpaired t test; n = 11 and 18 patients, respectively). In cells from the non-β-blocked patients, 5-HT produced a significant increase in the action potential duration at 50 % repolarisation, APD50 (measured at a constant pacing rate of 75 bpm), from 6 ± 1 to 17 ± 5 ms (P < 0.05, n = 15 cells, 7 patients). In these cells, 5-HT had no effect on the APD90 or the effective refractory period (ERP), at 190 ± 21 and 193 ± 24 ms (n = 11, 7 patients), in the absence of 5-HT, and 206 ± 26 and 213 ± 25 ms, in its presence, respectively. In the patients treated with β-blockers, 5-HT significantly increased the APD50, from 12 ± 4 to 44 ± 9 ms (P < 0.05). In these cells, 5-HT had no effect on the APD90 or the ERP, at 236 ± 20 and 246 ± 19 ms, in the absence of 5-HT, and 224 ± 24 and 244 ± 18 ms, in its presence. In the cells from patients treated with β-blockers, the 5-HT-induced prolongation of APD50 was significantly greater (absolute prolongation: 32 ± 8 ms) than in the untreated patients (11 ± 5 ms; P < 0.05). Moreover, abnormal automaticity occurred in response to 5-HT, in 5 cells (4 patients) of the 21 cells (12 patients) studied in the patients treated with β-blockers but was not recorded in any of the cells from the patients who were not treated with β-blockers.
In conclusion, these data suggest that in the human atrium, chronic β-blockade was associated with a more pronounced effect of 5-HT to prolong early repolarisation and induce automaticity.
This work was supported by Johnson & Johnson Pharmaceutical Research and Development.