Multivariate analysis demonstrated that LVEF <= 45% was the independent predictor for cardiac events. Nevertheless, Delta EDV >= 5ml was also an independent parameter, in addition GPCR Compound Library to LVEF <= 45%, to predict the combined endpoint of cardiac death, myocardial infarction, and revascularization, but excluding heart failure.\n\nConclusions: These results indicate that post-ischemic stunning, as assessed by gated SPECT, is a marker for poor prognosis, particularly for ischemic cardiac events. (Circ J 2010; 74: 1591-1599)”
“As our understanding of inflammatory resolution increases, drugs that trigger proresolution pathways

may become significant in treating chronic inflammatory diseases. However, anti-inflammatory drugs are traditionally tested during the first hours of onset (i.e., to dampen leukocyte and edema formation), and their ability to trigger proresolution processes has never been investigated. Moreover, there is no model available to screen for putative proresolving agents. In this study, we

present a new strategy to identify therapeutics for their ability to switch inflammation off and restore homeostasis. Injecting 1.0 GSK1120212 chemical structure mg of zymosan i.p. causes transient inflammation characterized by polymorphonuclear neutrophil clearance and dominated by recently described resolution-phase macrophages along with an innate-type lymphocyte repopulation, the latter being a marker of tissue homeostasis. In contrast, 10 mg of zymosan elicits find more an aggressive response characterized by classically activated macrophages leading to systemic inflammation and impaired lymphocyte repopulation. Although this latter model eventually resolves, it nonetheless represents inflammation in the

clinically relevant setting of polymorphonuclear neutrophil/classically activated macrophage dominance driving a cytokine storm. Treating such a reaction therapeutically with proresolution drugs provides quantifiable indices of resolution-polymorphonuclear neutrophil/macrophage clearance, macrophage phenotype switching (classically activated to resolution phase), and repopulation with resolution-phase lymphocytes-cardinal signs of inflammatory resolution and homeostasis in the peritoneum. As an illustration, mice bearing peritonitis induced by 10 mg of zymosan- were given ibuprofen, resolvin El, a prostaglandin D(2) receptor 1 agonist, dexamethasone, rolipram, or azithromycin, and their ability to trigger resolution and homeostasis in this new inflammatory setting was investigated. We present the first model for testing drugs with targeted proresolution properties using quantifiable parameters of inflammatory resolution and homeostasis. The Journal of Immunology, 2010, 184: 1516-1525.