title: Hyperglycemia contributes to cardiac dysfunction in a lipopolysaccharide-induced systemic inflammation model.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Lipopolysaccharide (LPS) was administered intravenously to rats, with or without the administration of insulin with glucose.
  
  
  METHODS
  University Medical Center research laboratory.
  
  
  METHODS
  Male Wistar rats.
  
  
  METHODS
  In this study, we determined the effect of hyperglycemia and insulin therapy on cardiac function in an LPS-induced systemic inflammation model.
  
  
  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.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, Yufu City, Oita, Japan. saku@med.oita-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Akira
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Asai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000097:blood; D006943:Hyperglycemia / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D009206:Myocardium / Q000473:pathology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume / Q000502:physiology*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D017725:Ventricular Pressure / Q000502:physiology*
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; D007004:Hypoglycemic Agents; D007328:Insulin; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites