Cardioprotective effects of the Na+/H+-exchange inhibitor cariporide in infarct-induced heart failure

Objective: We investigated the effect of chronic treatment with the new Na/H+-exchange inhibitor, cariporide, on cardiac function and remodelling 6 w eeks after myocardial infarction (MI) in rats. Methods: Treatment with cari poride was commenced either 1 week pre or 30 min, 3 h. 24 h or 7 days after ligation of the left ventricular artery and was continued until haemodynam ic parameters were obtained 6 weeks after MI in conscious rats. Results: Co mpared to sham animals, untreated MI-controls developed pronounced heart fa ilure after 6 weeks. Basal left ventricular end-diastolic pressure (in mmHg ) was reduced in the groups in which cariporide was started 1 week pre (16. 0+/-1.7) or 30 min (12.5+/-1.1), 3 h (11.8+/-1.0) and 24 h (13.0+/-3.5) aft er MI compared to untreated MI-controls (22.4+/-1.5; P<0.01). Basal myocard ial contractility (in 1000 mmHg/s) was only increased when treatment was in itiated after 30 min (9.0+/-0.7), 3 h (8.5+/-0.3) and 24 h (8.0+/-0.7) comp ared to untreated MI-controls (5.8+/-0.7: P<0.05-0.01). Infarct size (in % of left ventricular circumference) was 40.0+/-2.1 in MI-controls and was de creased when treatment was begun after 30 min (32.6+/-2.7) or 3 h (32.4+/-2 .3) (P<0.05). In animals, in which cariporide was started 3 h after inducti on of MI, heart weight/body weight ratio was significantly decreased, indic ating reduced cardiac hypertrophy. When treatment started 7 days after MI, cariporide did not exert any beneficial actions on structural and functiona l cardiac parameters. Conclusion: Our results show for the first time that chronic treatment with the Na+/H+-exchange inhibitor cariporide engendered marked cardioprotective effects when commenced before and up to 24 h after MI. The optimal time Tol the start of treatment was between 30 min and 3 h post MI. (C) 2000 Elsevier Science B.V. All rights reserved.