Severity of regional myocardial dysfunction is not affected by cardiomyocyte apoptosis in non-ischemic heart failure

The role of myocardial apoptosis during the development of heart failure (HF), in the absence of coronary artery stenosis, is still debated. The aim of the study was to evaluate whether (similar to functional impairment) the activation of myocardial apoptosis follows a regional pattern in an established model of pacing-induced HF. HF was induced in adult male minipigs by rapid and sustained left ventricular (LV) epicardial pacing (n=8; n=5 healthy controls). Progressive regional derangement of the contractile function and perfusion was assessed by magnetic resonance imaging as LV end-systolic wall thickening (LVESWT) and relative upslope of signal intensity (LVRUSI, %) in the anterior/anterior-lateral (pacing site, PS) and infero-septal LV region (opposite site, OS). LV tissue from PS and OS was analyzed for biomarkers of cell apoptosis and injury. After 21 days of LV pacing, LVESWT was lower in the PS compared to OS (7.6 +/- 3.7 vs 24.16 +/- 3.6%, p < 0.05), and LV ejection fraction was 24.0 +/- 3.7 (p < 0.05 vs control). The mRNA expression of caspase (Casp)-3 was significantly higher in the PS of HF hearts than in controls (1.28 +/- 0.125 vs 0.82 +/- 0.10), but not Casp-9. Bcl-2 and Hsp72 expression was significantly increased in PS compared to control (0.90 +/- 0.60 vs 0.63 +/- 0.033; 0.72 +/- 0.10 vs 0.28 +/- 0.098), in the presence of a TNF-alpha level increased by 50.7%. The regional myocardial apoptotic index, assessed by TUNEL, was unchanged in HF. In conclusion, the activators and inhibitors of cell apoptosis are equally expressed without affecting the survival of cardiomyocytes and the magnitude of regional myocardial dysfunction during development of non-ischemic HF. (C) 2010 Elsevier Ltd. All rights reserved.