The Effect of Ivabradine on the Human Atrial Myocardial Contractility in an In Vitro Study

PURPOSE: Ivabradine has emerged as a new antiarrhythmic agent that could compete with the traditional ones, such as beta-blockers. This experimental study aims to ascertain whether ivabradine directly interferes with the myocardial contractility in an in vitro environment. METHODS: Myocardial tissues from the right atrial appendages of patients undergoing cardiac surgery were dissected to obtain 40 specimens from 20 patients (length: 3 mm), which were exposed to electrical impulses at a frequency of 75 bpm for 30 min to reach a steady state. Specimens were then categorised into four groups (each including five patients). The first group was the control, whereas the second, third, and fourth were treated with 60 nM, 200 nM, and 2 μM ivabradine, respectively. We assessed five different contraction parameters before and after a 15 min treatment and calculated their relative changes, which were then compared to the control group. RESULTS: Ivabradine has affected the force of contraction significantly in vitro (p=0.009). However, force of contraction decreased in both the control group (93.5 ± 4.7%) and the second group (94.1 ± 4.5%, p=0.8) and force of contraction remained unchanged in the third group (101.0 ± 4.1%, p=0.24) and increased significantly in the fourth group (108.9 ± 11.6%, p=0.008). There was no change in other contraction parameters, such as passive tension force (97.1 ± 5.1%, p=0.368), duration of contraction (99.1 ± 4.3%, p=0.816), time to peak (96.6 ± 3.0%, p=0.536), and time to relaxation (101.2 ± 7.0%, p=0.564). CONCLUSIONS: Ivabradine did not interfere with the contractile behaviour of human atrial tissue when it was used in therapeutic dosages in vitro. However, it increased the contractility slightly, when it was used in supratherapeutic dosage.