Myocardial expression of a dominant-negative form of Daxx decreases infarct size and attenuates apoptosis in an in vivo mouse model of ischemia/reperfusion injury.

BACKGROUND: Apoptosis has been described extensively in acute myocardial infarction and chronic heart failure. Because Daxx (death-associated protein) appears to be essential for stress-induced cell death and acts as an antisurvival molecule, we tested the hypothesis that Daxx is involved in myocardial ischemia/reperfusion-induced cell death in vivo. METHODS AND RESULTS: Transgenic mice overexpressing a dominant-negative form of Daxx (Daxx-DN) under the control of the beta-actin promoter and control wild-type mice underwent an ischemia/reperfusion protocol: 40 minutes of left coronary artery occlusion and 60 minutes of reperfusion. Area at risk and infarct size were measured after dual staining by triphenyltetrazolium chloride and phthalocyanine blue dye. Apoptosis was measured in the ischemic versus the nonischemic part of the left ventricle by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling staining, enzyme-linked immunosorbent assay, and Western blotting of caspase-3, caspase-8, and poly(ADP-ribose) polymerase. The mitogen-activated protein kinase status was investigated by Western blot analysis. Comparison between groups was assessed by ANOVA or Student t test (statistical significance: P<0.05). Left ventricle tissues from transgenic mice expressed Daxx-DN at the protein level. Area at risk/left ventricle values were comparable among groups. Infarct size/area at risk was 45% reduced in Daxx-DN versus wild-type mice (P<0.001). This cardioprotection was maintained for a 4-hour reperfusion. Ischemia/reperfusion-induced apoptosis was significantly decreased and ERK1/2 prosurvival pathway was activated in ischemic Daxx-DN hearts. CONCLUSIONS: Our study clearly indicates that Daxx participates in myocardial ischemia/reperfusion proapoptotic signaling in vivo

083: Medical hypothesis: heart rate on admission and CRP are correlated, in acute pericarditis: a link between heart rate and pericardial inflammation?

IntroductionRest is usually recommended in acute pericarditis, as it could help to lower heart rate (HR) and contribute to limit “mechanical inflammation”. Whether HR on admission could be correlated and perhaps participate to inflammation has not been reported.MethodsBetween March 2007 and February 2010, we conducted a retrospective study on all patients admitted in our center for acute pericarditis. Diagnosis criteria included 2 among the following: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical ECG findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. We evaluated also recurrences and clinical events during hospitalization and at one month.ResultsWe included 73 patients. Median age was 38.0 y (CI 25-75% 28.0-51.0) and median hospitalization duration was 2.0 d (1.5-3.0). 27% of the patients presented pericardial effusion. Heart rate on admission was 88.0 bpm (CI 25-75%: 76.0-100.0) and on discharge 72.0 (65.0-80.0)). Heart rate on admission was significantly correlated with CRP on admission (r=0.34, n=69; p=0.004), CRP peak (r=0.54; n=61; p<0.0001), CRP on discharge (r=0.32; p=0.021) and temperature on admission (r=0.40; n=39; p=0.01). Multivariate analysis showed that HR on admission is associated with an elevated CRP peak, independently of temperature on admission. Fever was scarcely observed (19.5%), and was neither correlated to HR nor CRP, after multivariate analysis.ConclusionIn acute pericarditis, HR on admission is independently correlated with CRP levels. These observations could suggest a link between HR and pericardial inflammation