2 research outputs found

    Intracoronary Levosimendan during Ischemia Prevents Myocardial Apoptosis

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    Background: Levosimendan is a calcium sensitizer that has been shown to prevent myocardial contractile depression in patients post cardiac surgery. This drug exhibits an anti-apoptotic property; however, the underlying mechanism remains elusive. In this report, we characterized the myocardial protective of levosimendan in preventing cardiomyocyte apoptosis and post-operative stunning in an experimental ischemia–reperfusion model. Methods: Three groups of pigs (n = 8 per group) were subjected to 40 min of global, cardioplegic ischemia followed by 240 min of reperfusion. Levosimendan (65 μg/kg body weight) was given to pigs by intravenous infusion (L-IV) before ischemia or intracoronary administration during ischemia (L-IC). The Control group did not receive any levosimendan. Echocardiography was used to monitor cardiac function in all groups. Apoptosis levels were assessed from the left ventricle using the terminal transferase mediated dUTP nick end labeling (TUNEL) assay and immunocytochemical detection of Caspase-3. Results: Pigs after ischemia–reperfusion had a much higher TUNEL%, suggesting that our treatment protocol was effective. Levels of apoptosis were significantly increased in Control pigs that did not receive any levosimendan (0.062 ± 0.044%) relative to those received levosimendan either before (0.02 ± 0.017%, p = 0.03) or during (0.02 ± 0.017%, p = 0.03) the ischemia phase. Longitudinal left ventricular contraction in pigs that received levosimendan before ischemia (0.75 ± 0.12 mm) was significantly higher than those received levosimendan during ischemia (0.53 ± 0.11 mm, p = 0.003) or Control pigs (0.54 ± 0.11 mm, p = 0.01). Conclusion: Our results suggested that pigs received levosimendan displayed a markedly improved cell survival post I–R. The effect on cardiac contractility was only significant in our perfusion heart model when levosimendan was delivered intravenously before ischemia

    Cardiac Function, Perfusion, Metabolism, and Innervation following Autologous Stem Cell Therapy for Acute ST-Elevation Myocardial Infarction. A FINCELL-INSIGHT Sub-Study with PET and MRI

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    Purpose: Beneficial mechanisms of bone marrow cell (BMC) therapy for acute ST-segment elevation myocardial infarct (STEMI) are largely unknown in humans. Therefore, we evaluated the feasibility of serial positron emission tomography (PET) and MRI studies to provide insight into the effects of BMCs on the healing process of ischemic myocardial damage. Methods: Nineteen patients with successful primary reteplase thrombolysis (mean 2.4 h after symptoms) for STEMI were randomized for BMC therapy (2.9 × 106 CD34+ cells) or placebo after bone marrow aspiration in a double-blind, multi-center study. Three days post-MI, coronary angioplasty, and paclitaxel eluting stent implantation preceded either BMC or placebo therapy. Cardiac PET and MRI studies were performed 7–12 days after therapies and repeated after 6 months, and images were analyzed at a central core laboratory. Results: In BMC-treated patients, there was a decrease in [11C]-HED defect size (−4.9 ± 4.0 vs. −1.6 ± 2.2%, p = 0.08) and an increase in [18F]-FDG uptake in the infarct area at risk (0.06 ± 0.09 vs. −0.05 ± 0.16, p = 0.07) compared to controls, as well as less left ventricular dilatation (−4.4 ± 13.3 vs. 8.0 ± 16.7 mL/m2, p = 0.12) at 6 months follow-up. However, BMC treatment was inferior to placebo in terms of changes in rest perfusion in the area at risk (−0.09 ± 0.17 vs. 0.10 ± 0.17, p = 0.03) and infarct size (0.4 ± 4.2 vs. −5.1 ± 5.9 g, p = 0.047), and no effect was observed on ejection fraction (p = 0.37). Conclusion: After the acute phase of STEMI, BMC therapy showed only minor trends of long-term benefit in patients with rapid successful thrombolysis. There was a trend of more decrease in innervation defect size and enhanced glucose metabolism in the infarct-related myocardium and also a trend of less ventricular dilatation in the BMC-treated group compared to placebo. However, no consistently better outcome was observed in the BMC-treated group compared to placebo
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