title: Hyperglycemia raises the threshold of levosimendan- but not milrinone-induced postconditioning in rat hearts.
abstract: BACKGROUND
  The authors examined whether milrinone and levosimendan could exert cardiac postconditioning effects in rats under normoglycemia and hyperglycemia, and whether the effects could be mediated by mitochondrial permeability transition pore (mPTP).
  
  
  METHODS
  Wistar rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received milrinone or levosimendan just before reperfusion under normoglycemic or hyperglycemic conditions with or without atractyloside, an mPTP opener.
  
  
  RESULTS
  Under normoglycemia, both 30 μg/kg milrinone (29 ± 12%) and 10 μg/kg levosimendan (33 ± 13%) reduced infarct size compared with that in the control (58 ± 7%). Under hyperglycemia, milrinone (34 ± 13%) reduced infarct size at the same dose as under normoglycemia. In contrast, neither 10 nor 30 μg/kg levosimendan protected hyperglycemic hearts, and only 100 μg/kg levosimendan (32 ± 9%) reduced infarct size compared with that in the hyperglycemic control (58 ± 13%). All of these cardioprotective effects under normoglycemia and hyperglycemia are abolished by atractyloside.
  
  
  CONCLUSIONS
  Milrinone and levosimendan exert postconditioning effects via inhibition of mPTP opening. Hyperglycemia raises the threshold of levosimendan-induced postconditioning, while milrinone-induced postconditioning is not influenced by hyperglycemia.
authors.affiliation: Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan. shumtmt@nagasaki-u.ac.jp
authors.forename: Shuhei
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Sungsam
authors.initials: S
authors.lastname: Cho
authors.forename: Shinya
authors.initials: S
authors.lastname: Tosaka
authors.forename: Ushio
authors.initials: U
authors.lastname: Higashijima
authors.forename: Takuji
authors.initials: T
authors.lastname: Maekawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hara
authors.forename: Koji
authors.initials: K
authors.lastname: Sumikawa
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology*; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D008297:Male; D020105:Milrinone / Q000494:pharmacology*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077464:Simendan; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D006835:Hydrazones; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011724:Pyridazines; D000077464:Simendan; D020105:Milrinone