Hyperglycemia contributes to cardiac dysfunction in a lipopolysaccharide-induced systemic inflammation model *.
Hagiwara, Satoshi MD, PhD; Iwasaka, Hideo MD, PhD; Hasegawa, Akira MD; Asai, Nobuhiko MD; Noguchi, Takayuki MD, PhD
Critical Care Medicine.
37(7):2223-2227, July 2009.
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Objectives: Hyperglycemia is frequently observed in nondiabetic patients during acute illness. Furthermore, intensive insulin therapy significantly reduces mortality and morbidity due to several critical illnesses, including cardiac or infectious diseases. The purpose of this study was to determine whether cardiac function is affected by hyperglycemia and its treatment with insulin.
Design: Lipopolysaccharide (LPS) was administered intravenously to rats, with or without the administration of insulin with glucose.
Setting: University Medical Center research laboratory.
Subjects: Male Wistar rats.
Interventions: In this study, we determined the effect of hyperglycemia and insulin therapy on cardiac function in an LPS-induced systemic inflammation model.
Measurements and Main Results: Levels of serum cytokines, nitrate/nitrite, and high-mobility group box 1 protein after LPS treatment were measured in hyperglycemic rats and those treated with insulin. The following parameters were examined to assess cardiac function in Langendorff-perfused hearts: left ventricular developed pressure, left ventricular end-diastolic pressure, and left ventricular pressure development during isovolumetric contraction ( dP/dtmax) and relaxation (-dP/dtmin). We observed that levels of cytokines, nitrate/nitrite, and high-mobility group box 1 significantly increased. However, treatment of hyperglycemic rats with insulin was associated with significantly less severe disease as assessed by cytokine levels. Furthermore, hyperglycemia was associated with decreased dP/dtmax and -dP/dtmin in Langendorff-perfused hearts of hyperglycemic rats, whereas insulin treatment improved these parameters.
Conclusions: Hyperglycemia was associated with the induction of various inflammatory mediators and an inhibition of cardiac function. Treatment of hyperglycemia with insulin protected against inflammation and cardiac dysfunction in a rat model of LPS-induced systemic inflammation. This improvement is likely because of the neutralization of deleterious effects associated with hyperglycemia and the specific actions of insulin on the inflammatory response.
(C) 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins