title: The effect of levosimendan on lung damage after myocardial ischemia reperfusion in rats in which experimental diabetes was induced.
abstract: BACKGROUND
  It is known that diabetic complications and lipid peroxidation are closely associated. During ischemia and reperfusion (IR), injury may occur in distant organs, as well as in tissues next to the region exposed to the ischemia, and the lungs can be one of the most affected of these organs. Therefore, this study investigated the effects of levosimendan on lung tissue and the oxidant-antioxidant system in diabetic rats.
  
  
  METHODS
  The study was conducted in 24 Wistar albino rats that were separated into four groups (C, control; DC, diabetic control; DIR, diabetic IR; and DIRL, diabetic IR levosimendan). Diabetes was induced in 18 rats using streptozotocin (55 mg/kg), and the animals were randomly separated into three groups after the effects of the diabetes became apparent. After a left thoracotomy, ischemia was performed on the myocardial muscle with the left main coronary artery (LAD) for 30 min in the DIR and DIRL groups. After ischemia, the LAD ligation was removed, and reperfusion was applied for 120 min. Single-dose intraperitoneal 12 μg/kg levosimendan was administered to group DIRL before the ischemia. Group DC was evaluated as the diabetic control group, and six rats were considered to be the control group (group C), in which thoracotomy was performed and then closed with no induction of myocardial ischemia. We measured the levels of malondialdehyde, as a lipid peroxidation end product, as well as catalase and glutathione S-transferase activities, as antioxidant enzymes in the lung tissue. Tissue samples were also examined histopathologically.
  
  
  RESULTS
  Neutrophil infiltration or aggregation in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.003, P = 0.026, and P = 0.026, respectively). Alveolar wall thickening in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.002, P = 0.002, and P = 0.006, respectively). In addition, the lung tissue damage score was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.001, P = 0.004, and P = 0.007, respectively). Finally, catalase and glutathione S-transferase activity levels were significantly higher in the DIR group compared with those observed in the C, DC, and DIRL groups.
  
  
  CONCLUSIONS
  Although diabetes increases lipid peroxidation, it suppresses antioxidant activity. Our results showed that levosimendan had a protective effect against lung damage secondary to IR in the rats with induced diabetes. We recommend that experimental and clinical studies be conducted to examine the effects of levosimendan at different doses and different IR durations on various organs for clinical use.
authors.affiliation: Department of Anaesthesiology and Reanimation, Gazi University School of Medicine, Ankara, Turkey.
authors.forename: Metin
authors.initials: M
authors.lastname: Alkan
authors.affiliation: Department of Thoracic Surgery, Gazi University School of Medicine, Ankara, Turkey. Electronic address: alicelik78@gmail.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Çelik
authors.affiliation: Department of Biochemistry, Gazi University School of Medicine, Ankara, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Bilge
authors.affiliation: Department of Anaesthesiology and Reanimation, Canakkale Onsekiz Mart University School of Medicine, Çanakkale, Turkey.
authors.forename: Hasan Ali
authors.initials: HA
authors.lastname: Kiraz
authors.affiliation: Department of Paediatric Dentistry, Gazi University Faculty of Dentistry, Ankara, Turkey.
authors.forename: Gülay
authors.initials: G
authors.lastname: Kip
authors.affiliation: Department of Cardiovasculary Surgery, Gazi University School of Medicine, Ankara, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Özer
authors.affiliation: Department of Anaesthesiology and Reanimation, Gazi University School of Medicine, Ankara, Turkey.
authors.forename: Volkan
authors.initials: V
authors.lastname: Şıvgın
authors.affiliation: Department of Pathology, Gazi University School of Medicine, Ankara, Turkey.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Erdem
authors.affiliation: Department of Anaesthesiology and Reanimation, Gazi University School of Medicine, Ankara, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Arslan
authors.affiliation: Department of Biochemistry, Gazi University School of Medicine, Ankara, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kavutçu
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004353:Drug Evaluation, Preclinical; D006835:Hydrazones / Q000627:therapeutic use*; D055370:Lung Injury / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D011724:Pyridazines / Q000627:therapeutic use*; D011897:Random Allocation; D017208:Rats, Wistar; D000077464:Simendan; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan
keywords: Antioxidant system; Diabetes mellitus; Distant organ damage; Ischemia–reperfusion; Levosimendan; Rat