© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Cardioprotective effects of the Na+/H+-exchange inhibitor cariporide in infarct-induced heart failure
aInstitute of Pharmacology, Christian-Albrechts-University Kiel, Hospitalstrasse 4, D-24105 Kiel, Germany
bDepartment of Pathology, Maastricht University, Maastricht, The Netherlands
* Corresponding author. Tel.: +49-431-597-3500; fax: +49-431-597-3522 th.unger{at}pharmakologie.uni-kiel.de
Objective: We investigated the effect of chronic treatment with the new Na+/H+-exchange inhibitor, cariporide, on cardiac function and remodelling 6 weeks after myocardial infarction (MI) in rats. Methods: Treatment with cariporide 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 haemodynamic parameters were obtained 6 weeks after MI in conscious rats. Results: Compared to sham animals, untreated MI-controls developed pronounced heart failure 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±2.5) after MI compared to untreated MI-controls (22.4±1.5; P<0.01). Basal myocardial contractility (in 1000 mmHg/s) was only increased when treatment was initiated after 30 min (9.0±0.7), 3 h (8.5±0.3) and 24 h (8.0±0.7) compared 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 decreased 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 induction of MI, heart weight/body weight ratio was significantly decreased, indicating reduced cardiac hypertrophy. When treatment started 7 days after MI, cariporide did not exert any beneficial actions on structural and functional 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 for the start of treatment was between 30 min and 3 h post MI.
KEYWORDS NHE, Na+/H+-exchanger; MI, myocardial infarction; LVP, left ventricular pressure; LVEDP, left ventricular end-diastolic pressure; dP/dtmax, myocardial contractility; MAP, mean arterial pressure; HR, heart rate; Car, cariporide; THW/BW, total heart weight to body weight ratio; IS, infarct size; nIML, non infarcted muscle length; mLVC, mean left ventricular circumference; dLV, inner left ventricular diameter; aS, average septal thickness
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