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BACKGROUND: Repetitive brief myocardial ischemia has been implicated in the pathogenesis of the ventricular dysfunction associated with ischemic cardiomyopathy and myocardial hibernation. In this study we examine the effects of repetitive ischemia and reperfusion (I/R) on murine myocardium. METHODS: C57/BL6 mice underwent daily 15 min left anterior descending coronary occlusions followed by reperfusion. After 3, 5, 7, 14, 21 and 28 days, echocardiographic studies were performed, and hearts of I/R and sham-operated animals were processed for histological examination. RESULTS: Histological studies showed no evidence of myocardial necrosis in the ischemic region. Quantitative assessment of collagen revealed a marked persistent interstitial deposition of collagen after seven days I/R in the anterior left ventricular wall (sham 4.6 +/- 2.0 %, I/R 21.5 +/- 6.5 %, p < 0.05). Echocardiographic studies showed persistent regional anterior wall dysfunction in I/R animals. Histological evaluation showed absence of neovessel formation. After discontinuation of the I/R protocol, fibrosis and regional ventricular dysfunction decreased within 60 days. CONCLUSIONS: Repetitive brief murine myocardial I/R induces reversible fibrotic remodeling and ventricular dysfunction, without myocardial infarction and necrosis, and may play a role in the pathogenesis of ischemic cardiomyopathy and myocardial hibernation.

Aims: Repetitive brief ischemia and reperfusion (I/R) is associated with ventricular dysfunction in development of ischemic cardiomyopathy. We investigated the role of matricellular protein and macrophage maturation marker osteopontin-1 (OPN) in our closed-chest murine model of repetitive I/R. Methods: Daily 15 minutes LAD-occlusion followed by reperfusion was performed for 3, 5 and 7 consecutive days in C57/Bl6 wildtype (WT) and OPN-/–mice (n=8/group). Hearts were examined echocardiographically and processed for histological and mRNA studies. Results: OPN mRNA-expression was induced 15-fold in Taqman-RT-PCR after 3d I/R in WT-mice followed by a transient chemokine induction and macrophage infiltration. This led to extensive interstitial fibrosis with global and regional left ventricular dysfunction and without myocardial infarction after 7d I/R. In contrast, OPN-/–mice showed microinfarctions in the ischemic region after 3d I/R followed by a scar formation. Total collagen area was comparable between the strains. The microinfarctions in OPN-/–mice showed dense collagen deposition and a strong macrophage infiltration after 5d I/R (27.9±12.7 cells/field, F4/80). The non-infarcted ischemic area in OPN-/–mice showed only loose interstitial collagen deposition and lower macrophage density (7.0±1.6/field) when compared to WT-mice (33.3±8.2/field; p

We report the case of a 54-year old man with end-stage heart disease in whom the malfunctioning valves of a Novacor LVAS needed to be replaced after 490 days of circulatory support. This procedure could be performed without cardiopulmonary bypass.