Exogenous high-mobility group box 1 improves myocardial recovery after acute global ischemia/reperfusion injury

Background High-mobility group box 1 (HMGB1) is a mediator of inflammation with dose-dependent effects. In the setting of regional myocardial infarction, a high-dose HMGB1 treatment decreases myocardial function, whereas low-dose HMGB1 improves function; however, it is unknown what role HMGB1 has in...

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Published in:Surgery 2011-03, Vol.149 (3), p.329-335
Main Authors: Abarbanell, Aaron M., MD, Hartley, Jacob A, Herrmann, Jeremy L., MD, Weil, Brent R., MD, Wang, Yue, PhD, Manukyan, Mariuxi C., MD, Poynter, Jeffrey A., MD, Meldrum, Daniel R., MD
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Biological and medical sciences
Cardiology. Vascular system
General aspects
HMGB1 Protein - therapeutic use
Interleukin-1 - analysis
Interleukin-10 - biosynthesis
Male
Medical sciences
Myocardial Reperfusion Injury - drug therapy
Myocardial Reperfusion Injury - physiopathology
Myocardium - pathology
Rats
Rats, Sprague-Dawley
Surgery
Vascular Endothelial Growth Factor A - biosynthesis
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Summary:Background High-mobility group box 1 (HMGB1) is a mediator of inflammation with dose-dependent effects. In the setting of regional myocardial infarction, a high-dose HMGB1 treatment decreases myocardial function, whereas low-dose HMGB1 improves function; however, it is unknown what role HMGB1 has in the setting of global ischemia/reperfusion (I/R) injury. We hypothesized that a low-dose HMGB1 treatment would improve myocardial functional recovery and decrease infarct size after global I/R injury in association with increased levels of cardioprotective paracrine factors and decreased inflammation. Methods Adult rat hearts were isolated and perfused using the Langendorff method and were subjected to global I/R and treatment with either the vehicle, 200-ng HMGB1, or 1-μg HMGB1. The treatment was administered during 1 min at the start of reperfusion, and myocardial function was measured for 60 min of reperfusion. At the end of reperfusion, the hearts were sectioned and incubated in triphenyltetrazolium chloride to assess myocardial infarct size or homogenized to measure levels of inflammatory cytokines and growth factors. Results Postischemic treatment with 200-ng HMGB1 significantly improved myocardial functional recovery after global I/R in association with decreased infarct size and decreased interleukin-1 (IL-1), IL-6, IL-10, and vascular endothelial growth factor (VEGF) levels. In addition, 1-μg HMGB1 decreased myocardial inflammation but did not result in subsequent improvement in functional recovery. Conclusion In the setting of global I/R, 200-ng postischemic HMGB1 treatment improves myocardial function and decreases infarct size in association with suppressed myocardial inflammation. These results suggest a potential role for exogenous HMGB1therapy in the acute postischemic period.
ISSN:0039-6060
1532-7361
DOI:10.1016/j.surg.2010.07.002