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

Circ J. 2008 Jun;72(6):1012-7. doi: 10.1253/circj.72.1012.

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/dt(max), decreased absolute value of LV- dP/dt(min), 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.

MeSH terms

  • Animals
  • Disease Models, Animal
  • HMGB1 Protein / metabolism*
  • Heart Rate
  • Lipopolysaccharides / toxicity
  • Male
  • Myocardial Contraction / physiology*
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Pilot Projects
  • Rats
  • Rats, Wistar
  • Shock, Septic / chemically induced
  • Shock, Septic / metabolism*
  • Shock, Septic / physiopathology*
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Pressure

Substances

  • HMGB1 Protein
  • Lipopolysaccharides