Neutrophil-mediated accumulation of 2-ClHDA during myocardial infarction: 2-ClHDA-mediated myocardial injury

2005 ◽  
Vol 288 (6) ◽  
pp. H2955-H2964 ◽  
Author(s):  
Arun K. Thukkani ◽  
Bradley D. Martinson ◽  
Carolyn J. Albert ◽  
George A. Vogler ◽  
David A. Ford
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Damage ◽  
Neutrophil Infiltration ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Fatty Aldehyde ◽  
Infarct Zone ◽  
Ventricular Performance ◽  
Rat Hearts ◽  
Reactive Chlorinating Species

The pathophysiological sequelae of myocardial infarction include neutrophil infiltration into the infarct zone that contributes to additional damage to viable tissue and removal of cellular debris from necrosed tissue. Reactive chlorinating species produced by myeloperoxidase amplify the oxidant capacity of activated neutrophils. Plasmalogens are a major phospholipid subclass of both endothelial cells and cardiac myocytes. Recent studies have shown that plasmalogens are targeted by neutrophil-derived reactive chlorinating species that lead to the production of α-chloro fatty aldehydes. Results herein demonstrate that the α-chloro fatty aldehyde 2-chlorohexadecanal (2-ClHDA) accumulates in rat hearts subjected to left anterior descending coronary artery occlusion. Myocardia from rats subjected to surgical infarction had increased 2-ClHDA and neutrophil infiltration levels compared with myocardia from rats subjected to sham surgery. Additionally, infarcted myocardia from rats rendered neutropenic by treatments with an anti-neutrophil antibody had diminished 2-ClHDA and neutrophil infiltration levels compared with infarcted myocardia from normopenic rats; 2-ClHDA was shown to elicit myocardial damage as determined by lactate dehydrogenase release in isolated perfused rat hearts. Additionally, 2-ClHDA treatment of hearts resulted in decreased heart rate and ventricular performance. Taken together, the present results demonstrate a novel neutrophil-dependent myeloperoxidase-based mechanism that results in 2-ClHDA production in response to regional myocardial infarction that may also contribute to cardiac dysfunction.

dl-3-Hydroxybutyrate administration prevents myocardial damage after coronary occlusion in rat hearts

2002 ◽  
Vol 283 (5) ◽  
pp. H1968-H1974 ◽  
Author(s):  
Zhitian Zou ◽  
Shiro Sasaguri ◽  
Katare Gopalrao Rajesh ◽  
Ryoko Suzuki
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Rat Hearts ◽  
High Concentrations ◽  
Myocardial Infarction Size

To investigate the role of high concentrations of dl-3-hydroxybutyrate (DL-3-HB) in preventing heart damage after prolonged fasting, infarct size and the incidence of apoptosis caused by ischemia-reperfusion were determined in four groups of Wistar rats. Fed rats (±DL-3-HB group) and fasted rats (±DL-3-HB group) were subjected to 30 min of left coronary artery occlusion and 120 min of reperfusion. DL-3-HB was administered intravenously 60 min before the coronary artery occlusion. Infarct size, defined by triphenylyetrazolium chloride (TTC) staining, was reduced from 72 ± 3% (fed group), 75 ± 5% (fed + DL-3-HB group), and 70 ± 5% (fasting group), respectively, to 26 ± 4% ( P < 0.01 vs. fasting + DL-3-HB group). Apoptosis, as defined by single-stranded DNA staining, was significantly reduced in the subendocardial region in the fasting + DL-3-HB group (9 ± 2%) compared with the other groups (39 ± 6% in the fed group, 37 ± 5% in the fed + DL-3-HB group, and 34 ± 3% in the fasting group; P < 0.01). In addition, levels of ATP in the fasting + DL-3-HB group were significantly higher compared with other groups after 30 min of ischemia and 120 min of reperfusion ( P < 0.01). In conclusion, the present study demonstrates that high concentrations of DL-3-HB reduces myocardial infarction size and apoptosis induced by ischemia-reperfusion, possibly by providing increased energy substrate to the fasted rat myocardium.

Some Problems Concerning Coronary Artery Occlusion and Acute Myocardial Infarction

Circulation ◽  
1969 ◽  
Vol 40 (5s4) ◽  
Author(s):  
DONALD B. HACKEL ◽  
E. HARVEY ESTES ◽  
ABE WALSTON ◽  
STEPHEN KOFF ◽  
EUGENE DAY
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Coronary Artery ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion

Abstract 12: EMMPRIN-Targeted Magnetic Nanoparticles for in vivo Visualization and Regression of Acute Myocardial Infarction in a Model of Acute Coronary Artery Occlusion

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Irene Cuadrado ◽  
Maria Jose Garcia Miguel ◽  
Irene Herruzo ◽  
Mari Carmen Turpin ◽  
Ana Martin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Extracellular Matrix ◽  
Coronary Artery ◽  
Left Ventricle ◽  
Infarct Size ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Gadolinium Enhancement

Extracellular matrix metalloproteinase inducer EMMPRIN, is highly expressed in patients with acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including MMP-9 and MMP-13. To prevent Extracellular matrix degradation and cardiac cell death we targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles with an EMMPRIN binding peptide AP9 conjugated (NAP9), or an AP9 scramble peptide as a negative control (NAPSC). NAP9 binds to endogenous EMMPRIN as detected by confocal microscopy of cardiac myocytes and macrophages incubated with NAP and NAPSC in vitro, and in vivo in mouse hearts subjected to left anterior descending coronary artery occlusion (IV injection 50mγ/Kg NAP9 or NAP9SC). Administration of NAP9 at the same time or 1 hour after AMI reduced infarct size over a 20% respect to untreated and NAPSC injected mice, recovered left ventricle ejection fraction (LVEF) similar to healthy controls, and reduced EMMPRIN downstream MMP9 expression. In magnetic resonance scans of mouse hearts 2 days after AMI and injected with NAP9, we detected a significant gadolinium enhancement in the left ventricle respect to non-injected mice and to mice injected with NAPSC. Late gadolinium enhancement assays exhibited NAP9-mediated left ventricle signal enhancement as early as 30 minutes after nanoprobe injection, in which a close correlation between the MRI signal enhancement and left ventricle infarct size was detected. Taken together, these results point EMMPRIN targeted nanoprobes as a new tool for the treatment of AMI.

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