Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Experimental Investigation
High Mobility Group Box 1 Induces a Negative Inotropic Effect on the Left Ventricle in an Isolated Rat Heart Model of Septic Shock
A Pilot Study
Satoshi HagiwaraHideo IwasakaTomoko UchinoTakayuki Noguchi
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2008 Volume 72 Issue 6 Pages 1012-1017

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Abstract

Background Sepsis can be exacerbated by an inappropriate immune response and the severe impact of this disease on the cardiovascular system is well documented. High mobility group box 1 (HMGB1) protein is an important mediator in the pathogenesis of sepsis and its role in cardiovascular system dysfunction was investigated in an lipopolysaccharide (LPS)-induced rat model of sepsis. Methods and Results Twelve hours after intravenous bolus injections of LPS (5 mg/kg), rats were killed and heart samples were harvested. Immunoblot analysis was performed to assess expression levels of HMGB1 in cardiac myocytes. Left ventricular developed pressure (LVDP) served as a measure of systolic function. LPS administration was associated with an increase in the expression of HMGB1 in cardiac myocytes and a decrease in cardiac function. Hearts from the LPS-treated rats were also perfused with recombinant HMGB1 and cardiac function measured. The dose-dependent effects observed with elevated HMGB1 included decreased LVDP, decreased left ventricular (LV) + dP/dtmax, decreased absolute value of LV- dP/dtmin, and increased LV end-diastolic pressure. Conclusions HMGB1 stimulation produces a negative inotropic effect during septic shock, suggesting an important role for this molecule in cardiovascular system dysfunction during sepsis. (Circ J 2008; 72: 1012 - 1017)

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© 2008 THE JAPANESE CIRCULATION SOCIETY
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