Effects of SM-20550 against myocardial infarction-induced arrhythmias, late infarct expansion, and left ventricular dysfunction.
The aim of the study was to evaluate the cardioprotective and antiarrhythmic effects of intravenous Na+/H+ blockers (cariporide and SM-20550) in a rat model of ischemia and a long period reperfusion (14 days). This model allowed study of the role of Na+/H+ exchanger against late myocardial infarct expansion and left ventricular dysfunction. Each compound was administered 5 min before ischemia. Cariporide (from 0.16 mg/kg) and SM-20550 (from 0.04 mg/kg) significantly and dose-dependently reduced the number of ventricular premature beats during ischemia. The duration of ventricular tachycardia was importantly shortened in the presence of cariporide (0.63 mg/kg) and SM-20550 (0.16 mg/kg). Furthermore, cariporide (0.63 mg/kg) and SM-20550 (from 0.04 mg/kg) significantly reduced the infarct expansion: 43 +/- 2% in the cariporide group and 42 +/- 2% at 0.16 mg/kg SM-20550 versus 48 +/- 1% in the vehicle group. Cariporide and SM-20550 significantly prevented the left ventricular free wall thinning associated with the thickness ratio, suggesting a significant reduction of the ventricular dilation. Cariporide and SM-20550 significantly improved the negative dP/dtmax, suggesting a partial restoration of the cardiac relaxation. Collectively, Na+/H+ blockers administered before ischemia reduced arrhythmias and also prevented the remodeling process of the heart during postinfarction.
Grosjean
Noëlle
N
Centre de Recherche Pierre Fabre, Divisions of Cardiovascular Diseases, Castres, France.
Vié
Bruno
B
Létienne
Robert
R
Le  Grand
Bruno
B
D000578:Amidines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000187:drug effects*
D000578:Amidines; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D006146:Guanidines; D007211:Indoles; C121094:SM 20550; D013450:Sulfones; D004280:Dobutamine; C093373:cariporide