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

概要

論文の詳細を見る
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 HMGB 1 in cardiac myocytes and a decrease in cardiac function. Hearts from the LPS-treated rats were also perfused with recombinant HMGB 1 and cardiac function measured. The dose-dependent effects observed with elevated HMGB 1 included decreased LVDP, decreased left ventricular (LV)+dP/dt_<max>, decreased absolute value of LV-dP/dt_<min>, and increased LV end-diastolic pressure. Conclusions HMGB 1 stimulation produces a negative inotropic effect during septic shock, suggesting an important role for this molecule in cardiovascular system dysfunction during sepsis.
2008-05-20