Comparison of a beta-blocker and an If current inhibitor in rabbits with myocardial infarction.

Aim: We compared protective effects of a ss-adrenoceptor blocker (metoprolol; Met) and a If current (Ivabradine; Iva) in a rabbit model of myocardial infarction.

Methods: Experiments were performed on 44 adult New-Zealand-White (NZW) rabbits. The effects of either metoprolol or ivabradine were assessed 15 min after experimental occlusion of a coronary artery (CAO), 28 days after CAO (drug gavage), and in vitro hearts (Langendorff apparatus). The results were compared with sham and placebo hearts.

Results: Metoprolol (0.25 mg/kg) slightly reduced heart rate and left ventricular systolic function. Ivabradine (0.25 mg/kg) reduced heart rate significantly (P<0.05) (18% vs control). Both drugs provided advantages over placebo: mortality was significantly (P<0.01)smaller (6/13 Pla animals died, 2/10 Met animals, and 3/11 Iva animals), left ventricular function was better preserved after 28 days (external power; Pla; Met; Iva=56%; 76%; 74%), and dilatation (BNP) was reduced (P<0.05). In the Pla group, the ST segment was significantly (P<0.05) elevated by 0.35 mV after CAO and exhibited in 50% of the animals Q waves after 28 days, while after ivabradine or metoprolol, ST displacement and Q waves had disappeared. The uneconomic myosin isoenzyme V3 predominated in Met hearts and Iva hearts (V3/V1: 63/37% and 62/38%), while it was further increased in Pla hearts (78/21%). External efficiency was lowest in Pla hearts (1.00+/-0.50 a.u.; P<0.05) and was significantly higher both in Met hearts (4.0+/-1.8 a.u.) and in Iva hearts (3.3+/-1.6 a.u.).

Conclusions: Met and Iva seem suited for the treatment of chronic myocardial infarction.