Circulation
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Comparative Study
Combined tyrosine and serine/threonine kinase inhibition by sorafenib prevents progression of experimental pulmonary hypertension and myocardial remodeling.
Inhibition of tyrosine kinases, including platelet-derived growth factor receptor, can reduce pulmonary arterial pressure in experimental and clinical pulmonary hypertension. We hypothesized that inhibition of the serine/threonine kinases Raf-1 (also termed c-Raf) and b-Raf in addition to inhibition of tyrosine kinases effectively controls pulmonary vascular and right heart remodeling in pulmonary hypertension. ⋯ The multikinase inhibitor sorafenib prevents pulmonary remodeling and improves cardiac and pulmonary function in experimental pulmonary hypertension. Sorafenib exerts direct myocardial antihypertrophic effects, which appear to be mediated via inhibition of the Raf kinase pathway. The combined inhibition of tyrosine and serine/threonine kinases may provide an option to treat pulmonary arterial hypertension and associated right heart remodeling.
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Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events. ⋯ Lipid profiles at most change minimally in response to normal food intake in individuals in the general population. Furthermore, nonfasting lipid profiles predicted increased risk of cardiovascular events.
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The Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials evaluated fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST- and ST-segment elevation acute coronary syndromes, respectively. Combined results for these 2 trials on major efficacy and safety outcomes and data on the effects of fondaparinux in relation to interventional management strategy have not been previously reported. ⋯ Compared with a heparin-based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of acute coronary syndromes and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.
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Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model. ⋯ Reperfusion injury was significantly alleviated by basic modifications of the initial reperfusion period in a new in vivo model of acute limb ischemia. With this model, systematic optimizations of according protocols may eventually translate into improved clinical management of acute limb ischemia.