title: Levosimendan attenuates multiple organ injury and improves survival in peritonitis-induced septic shock: studies in a rat model.
abstract: BACKGROUND
  The aim of this study was to investigate the effects of levosimendan on rodent septic shock induced by cecal ligation and puncture (CLP).
  
  
  METHODS
  Three hours after peritonitis-induced sepsis, male Wistar rats were randomly assigned to receive an intravenous infusion of levosimendan (1.2 μg/kg/min for 10 min and then 0.3 μg/kg/min for 6 h) or an equivalent volume of saline and vehicle (5% dextrose) solution.
  
  
  RESULTS
  The levosimendan-treated CLP animals had significantly higher arterial pressure and lower biochemical indices of liver and kidney dysfunction compared to the CLP animals (P < 0.05). Plasma interleukin-1β, nitric oxide and organ superoxide levels in the levosimendan-treated CLP group were less than those in CLP rats treated with vehicle (P < 0.05). In addition, the inducible nitric oxide synthase (iNOS) in lung and caspase-3 expressions in spleen were significantly lower in the levosimendan-treated CLP group (P < 0.05). The administration of CLP rats with levosimendan was associated with significantly higher survival (61.9% vs. 40% at 18 h after CLP, P < 0.05). At postmortem examination, the histological changes and neutrophil filtration index in liver and lung were significantly attenuated in the levosimendan-treated CLP group (vs. CLP group, P < 0.05).
  
  
  CONCLUSIONS
  In this clinically relevant model of septic shock induced by fecal peritonitis, the administration of levosimendan had beneficial effects on haemodynamic variables, liver and kidney dysfunction, and metabolic acidosis. (1) Lower levels of interleukin-1β, nitric oxide and superoxide, (2) attenuation of iNOS and caspase-3 expressions, and (3) decreases of neutrophil infiltration by levosimendan in peritonitis-induced sepsis animals suggest that anti-inflammation and anti-apoptosis effects of levosimendan contribute to prolonged survival.
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan. cm.cmtsao@gmail.com.|Department of Anesthesiology, Tri-Service General Hospital, National Defence Medical Centre, Taipei, Taiwan. cm.cmtsao@gmail.com.
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Tsao
authors.affiliation: Department of Pharmacology, National Defence Medical Centre, Neihu PO Box 90048-504, Taipei, 114, Taiwan. keilee1108@yahoo.com.tw.
authors.forename: Kai-Yi
authors.initials: KY
authors.lastname: Li
authors.affiliation: Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan. sjchen@knjc.edu.tw.|Department of Physiology, National Defence Medical Centre, Taipei, Taiwan. sjchen@knjc.edu.tw.
authors.forename: Shiu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Aerospace and Undersea Medicine, National Defence Medical Centre, Taipei, Taiwan. shukmanka@gmail.com.
authors.forename: Shuk-Man
authors.initials: SM
authors.lastname: Ka
authors.affiliation: Department of Anesthesiology, Tri-Service General Hospital, National Defence Medical Centre, Taipei, Taiwan. siculiaw@gmail.com.|Department of Pharmacology, National Defence Medical Centre, Neihu PO Box 90048-504, Taipei, 114, Taiwan. siculiaw@gmail.com.|Department of Anesthesiology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan. siculiaw@gmail.com.
authors.forename: Wen-Jinn
authors.initials: WJ
authors.lastname: Liaw
authors.affiliation: Department of Anesthesiology, Cheng-Hsin General Hospital, Taipei, Taiwan. 85757067huang@gmail.com.|Department of Anesthesiology and Pain Clinics, Cheng-Hsin Rehabilitation Medical Centre, 45, Cheng-Hsin St, Taipei, 112, Taiwan. 85757067huang@gmail.com.
authors.forename: Hsieh-Chou
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, National Defence Medical Centre, Neihu PO Box 90048-504, Taipei, 114, Taiwan. ccwu@mail.ndmctsgh.edu.tw.|Department of Pharmacology, Taipei Medical University, Taipei, Taiwan. ccwu@mail.ndmctsgh.edu.tw.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Wu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006835:Hydrazones / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D009102:Multiple Organ Failure / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010538:Peritonitis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011724:Pyridazines / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077464:Simendan; D015996:Survival Rate / Q000639:trends
chemical_list: D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan