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-inflammat...

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Published in:International journal of cardiology 2013-10, Vol.168 (4), p.3412-3418
Main Authors: Palus, Sandra, von Haehling, Stephan, Flach, Valerie C, Tschirner, Anika, Doehner, Wolfram, Anker, Stefan D, Springer, Jochen
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Body composition
Cachexia - drug therapy
Cachexia - physiopathology
Cancer cachexia
Cardiac function
Cardiac Output - drug effects
Cardiac Output - physiology
Cardiology. Vascular system
Cardiovascular
Dose-Response Relationship, Drug
Gastroenterology. Liver. Pancreas. Abdomen
Heart
Heart Rate - drug effects
Heart Rate - physiology
Hepatoma
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Neoplasms - drug therapy
Neoplasms - physiopathology
Random Allocation
Rats
Rats, Wistar
Simvastatin
Simvastatin - pharmacology
Simvastatin - therapeutic use
Stroke Volume - drug effects
Stroke Volume - physiology
Survival
Treatment Outcome
Tumors
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Summary: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). Conclusion 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.
ISSN:0167-5273
1874-1754
DOI:10.1016/j.ijcard.2013.04.150