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

doi:10.1016/S0008-6363(99)00428-9

Cardiovascular Research 2000 46(1):102-110; doi:10.1016/S0008-6363(99)00428-9
© 2000 by European Society of Cardiology

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

Heidi Spitznagel^a, Oliver Chung^a, Qin-Gui Xia^a, Birthe Rossius^a, Sascha Illner^a, Gunnar Jähnichen^a, Steffen Sandmann^a, Alexander Reinecke^a, Mat J.A.P. Daemen^b and Thomas Unger^a^,*

^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 withthe new Na⁺/H⁺-exchange inhibitor, cariporide, on cardiac functionand remodelling 6 weeks after myocardial infarction (MI) inrats. Methods: Treatment with cariporide was commenced either1 week pre or 30 min, 3 h, 24 h or 7 days after ligation ofthe left ventricular artery and was continued until haemodynamicparameters were obtained 6 weeks after MI in conscious rats.Results: Compared to sham animals, untreated MI-controls developedpronounced heart failure after 6 weeks. Basal left ventricularend-diastolic pressure (in mmHg) was reduced in the groups inwhich cariporide was started 1 week pre (16.0±1.7) or30 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±2.1in MI-controls and was decreased when treatment was begun after30 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 inductionof MI, heart weight/body weight ratio was significantly decreased,indicating reduced cardiac hypertrophy. When treatment started7 days after MI, cariporide did not exert any beneficial actionson structural and functional cardiac parameters. Conclusion:Our results show for the first time that chronic treatment withthe Na⁺/H⁺-exchange inhibitor cariporide engendered marked cardioprotectiveeffects when commenced before and up to 24 h after MI. The optimaltime for the start of treatment was between 30 min and 3 h postMI.

KEYWORDS NHE, Na⁺/H⁺-exchanger; MI, myocardial infarction; LVP, left ventricular pressure; LVEDP, left ventricular end-diastolic pressure; dP/dt_max, 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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