title: Simvastatin reduces wasting and improves cardiac function as well as outcome in experimental cancer cachexia.
abstract: BACKGROUND
  Chronic inflammation is common in cancer cachexia (CC) and directly involved in the atrophy seen in this condition. Recently, several groups have described a form of cardiomyopathy in CC animal models. Hence, we investigated the effect of simvastatin with its known anti-inflammatory and cardioprotective effects in a rat model of CC.
  
  
  METHODS
  Juvenile Wister Han rats (weight approx. 200 g) were inoculated with Yoshida AH-130 hepatoma cells and treated once daily with 0.1, 1, 10 or 20 mg/kg/d simvastatin or placebo for 14 days. Body weight and body composition (NMR) were assessed at baseline and at the end of the study. Cardiac function was analysed by echocardiography at baseline and day 11.
  
  
  RESULTS
  Tumour-bearing, placebo-treated rats lost 47.9±3.8 g of their initial body weight. Treatment with 0.1, 1, 10 or 20 mg/kg/d simvastatin significantly reduced wasting by 39.6%, 47.6%, 28.5% and 35.4%, respectively (all p<0.05 vs. placebo). This was mainly due to reduced atrophy of lean mass, i.e. muscle mass. Cardiac function was significantly improved, e.g. cardiac output (untreated sham: 78.9 mL/min) was severely impaired in tumour-bearing rats (42.4 mL/min) and improved by 1, 10 or 20 mg/kg/d simvastatin (62.2, 59.0 and 57.0 mL/min, respectively, all p<0.05 vs. placebo). Most importantly, 10 or 20 mg/kg/d simvastatin reduced mortality (HR:0.16, 95%CI:0.04-0.76, p=0.021 and HR:0.16, 95%CI:0.03-0.72, p=0.017 vs placebo, respectively).
  
  
  CONCLUSIONS
  Simvastatin attenuated loss of body weight as well as muscle mass and improved cardiac function leading to improved survival in this CC model. Simvastatin may be beneficial in a clinical setting to treat CC.
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany; Center for Cardiovascular Research, Charite Medical School, Berlin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Palus
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Flach
authors.forename: Anika
authors.initials: A
authors.lastname: Tschirner
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Jochen
authors.initials: J
authors.lastname: Springer
mesh_terms: D000818:Animals; D002100:Cachexia / Q000188:drug therapy* / Q000503:physiopathology; D002302:Cardiac Output / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D019821:Simvastatin
keywords: Body composition; Cancer cachexia; Cardiac function; Hepatoma; Simvastatin; Survival