Early Metoprolol Administration Before Coronary Reperfusion Results in Increased Myocardial Salvage Analysis of Ischemic Myocardium at Risk Using Cardiac Magnetic Resonance
Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. Circulation
(Impact Factor: 14.43).
07/2007; 115(23):2909-16. DOI: 10.1161/CIRCULATIONAHA.106.679639
Beta-blockers improve clinical outcome when administered early after acute myocardial infarction. However, whether beta-blockers actually reduce the myocardial infarction size is still in dispute. Cardiac magnetic resonance imaging can accurately depict the left ventricular (LV) ischemic myocardium at risk (T2-weighted hyperintense region) early after myocardial infarction, as well as the extent of necrosis (delayed gadolinium enhancement). The aim of this study was to determine whether early administration of metoprolol could increase myocardial salvage, measured as the difference between the extent of myocardium at risk and myocardial necrosis.
Twelve Yorkshire pigs underwent a 90-minute left anterior descending coronary occlusion, followed by reperfusion. They were randomized to metoprolol (7.5 mg during myocardial infarction) or placebo. Global and regional LV function, extent of myocardium at risk, and myocardial necrosis were quantified by cardiac magnetic resonance imaging studies performed 4 and 22 days after reperfusion in 10 survivors. Despite similar extent of myocardium at risk in metoprolol- and placebo-treated pigs (30.9% of LV versus 30.6%; P=NS), metoprolol resulted in 5-fold-larger salvaged myocardium (32.4% versus 6.2% of myocardium at risk; P=0.015). The LV ejection fraction significantly improved in metoprolol-treated pigs between days 4 and 22 (37.2% versus 43.0%; P=0.037), whereas it remained unchanged in pigs treated with placebo (35.1% versus 35.0%; P=NS). The extent of myocardial salvage was related directly to LV ejection fraction improvement (P=0.031) and regional LV wall motion recovery (P=0.039) at day 22.
Early metoprolol administration during acute coronary occlusion increases myocardial salvage. The extent of myocardial salvage, measured as the difference between myocardium at risk and myocardial necrosis, was associated with regional and global LV motion improvement.
Available from: Dennis Ladage
- "To determine scar size, we visualised delayed enhancement (DE) 15 minutes after the administration of 0.2 mmol/kg gadopentate dimeglumine (Magnevist, Bayer Medical Solutions) in an inversion-recovery fast gradient-echo sequence . LV function analysis was performed with Argus software (Argus, Siemens Medical Solutions). "
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ABSTRACT: Mammalian myocardium has a finite but limited capacity to regenerate. Experimentally stimulating proliferation of cardiomyocytes with extracellular regeneration factors like periostin enhances cardiac repair in rodents. The aim of this study was to develop a safe method for delivering regeneration factors to the heart and to test the functional and structural effects of periostin peptide treatment in a large animal model of myocardial infarction (MI).
We developed a controlled release system to deliver recombinant periostin peptide into the pericardial space. A single application of this method was performed two days after experimental MI in swine. Animals were randomly assigned to receive either saline or periostin peptide. Experimental groups were compared at baseline, day 2, 1 month and 3 months. Treatment with periostin peptide increased the EF from 31% to 41% and decreased by 22% the infarct size within 12 weeks. Periostin peptide-treated animals had newly formed myocardium strips within the infarct scar, leading to locally improved myocardial function. In addition the capillary density was increased in animals receiving periostin. However, periostin peptide treatment increased myocardial fibrosis in the remote region at one week and 12 weeks post-treatment.
Our study shows that myocardial regeneration through targeted peptides is possible. However, in the case of periostin the effects on cardiac fibrosis may limit its clinical application as a viable therapeutic strategy.
PLoS ONE 05/2013; 8(5):e59656. DOI:10.1371/journal.pone.0059656 · 3.23 Impact Factor
Available from: Gemma Vilahur
- "2.2. Model of myocardial ischemia/reperfusion (I/R) AMI was experimentally induced as we have previously described  . Briefly, 12 h prior to the experimental induction of acute MI, a loading dose of clopidogrel was administered to all animals. "
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ABSTRACT: The extent of cardiac remodeling determines survival after acute MI. However, the mechanisms driving cardiac remodeling remain unknown. We examined the effect of ischemia and reperfusion (R) on myocardial changes up to 6 days post-MI. Pigs underwent 1.5h or 4h mid-LAD balloon occlusion and sacrificed or 1.5h occlusion followed by R and sacrificed at 2.5h, 1 day, 3 days, and 6 days. Ischemic- (IM) and non-ischemic myocardium (NIM) was obtained for molecular analysis of: 1) apoptosis (P-Bcl2, Bax, P-p53, active-caspase-3); 2) the TLR-4-MyD88-dependent and independent pathways; 3) Akt/mTOR/P70(S6K) axis activation; and, 4) fibrosis (TGF-β, collagen1-A1/A3). Histopathology for inflammation, collagen, and fibroblast content, TUNEL staining, and metalloproteinase activity was performed. Apoptosis is only detected upon R in IM cardiomyocytes and progresses up to 6 days post-R mainly associated with infiltrated macrophages. The Akt/mTOR/P70(s6K) pathway is also activated upon R (IM) and remains elevated up to 6 days-R (P<0.05). Ischemia activates the TLR-4-MyD88-dependent (cytokines/chemokines) and -independent (IRF-3) pathways in IM and NIM and remains high up to 6 days post-R (P<0.05). Accordingly, leukocytes and macrophages are progressively recruited to the IM (P<0.05). Ischemia up-regulates pro-fibrotic TGF-β that gradually rises collagen1-A1/-A3 mRNA with subsequent increase in total collagen fibrils and fibroblasts from 3 days-R onwards (P<0.005). MMP-2 activity increases from ischemia to 3 days post-R (P<0.05). We report that there is a timely coordinated cellular and molecular response to myocardial ischemia and R within the first 6 days after MI. In-depth understanding of the mechanisms involved in tissue repair is warranted to timely intervene and better define novel cardioprotective strategies.
Journal of Molecular and Cellular Cardiology 03/2011; 50(3):522-33. DOI:10.1016/j.yjmcc.2010.12.021 · 4.66 Impact Factor
Available from: Michel Ovize
- "Cardiac MRI (CMR) may be a promising imaging technique for measuring the AAR. Animal studies have reported that enhanced signal intensity on retrospective T2-weighted CMR from increased myocardial oedema  correlates with the AAR in reperfused myocardial infarcts [1, 27]. Preliminary clinical studies suggest that the enhanced T2 signal intensity on CMR scans performed in the first week following PCI correlates with the AAR as measured by the BARI coronary angiography jeopardy score  and nuclear myocardial scans . "
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ABSTRACT: Ischemic heart disease (IHD) is the leading cause of death worldwide. Novel cardioprotective strategies are therefore required to improve clinical outcomes in patients with IHD. Although a large number of novel cardioprotective strategies have been discovered in the research laboratory, their translation to the clinical setting has been largely disappointing. The reason for this failure can be attributed to a number of factors including the inadequacy of the animal ischemia-reperfusion injury models used in the preclinical cardioprotection studies and the inappropriate design and execution of the clinical cardioprotection studies. This important issue was the main topic of discussion of the UCL-Hatter Cardiovascular Institute 6th International Cardioprotection Workshop, the outcome of which has been published in this article as the "Hatter Workshop Recommendations". These have been proposed to provide guidance on the design and execution of both preclinical and clinical cardioprotection studies in order to facilitate the translation of future novel cardioprotective strategies for patient benefit.
Archiv für Kreislaufforschung 11/2010; 105(6):677-86. DOI:10.1007/s00395-010-0121-4 · 5.41 Impact Factor
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