Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure

摘要: Objective : Experimental evidence suggests that modulation of myocardial substrate metabolism can markedly affect the progression chronic heart failure (HF). We tested whether inhibition carnitine palmitoyl transferase-I (CPT-I), enzyme regulating mitochondrial fatty acid oxidation, slows left ventricular remodeling and deterioration function in pacing-induced HF. Methods Normal dogs ( n =9) were compared to untreated with HF treated 65 mg/kg/day oxfenicine (HF+Oxf, =9), a CPT-I inhibitor. Results HF+Oxf reached terminal (LV end-diastolic pressure=25 mm Hg) 6 days later than P <0.05). At 28 pacing, hemodynamic alterations LV dilation significantly attenuated 25% decrease wall thickness was completely prevented vs. HF, as activation matrix metalloproteinase-2 -9, markers tissue remodeling. Oxfenicine also HF-induced transcriptional down-regulation CPT-I, medium chain acyl-CoA dehydrogenase, GAPDH citrate synthase, key enzymes cardiac energy metabolism. In addition, mRNA, but not protein levels nuclear receptor peroxisome proliferator-activated receptor-α reduced while they did change HF+Oxf, control. Conclusions early development thinning delayed time end-stage failure. While these results are limited an experimental model disease, nevertheless suggest might be effective for slowing clinical HF.