The role of Actovegin in muscle injuries

Muscle injuries are one of the most common sports related injuries. An audit published by The Football Association (FA) in 2004, suggested that 12% of all injuries were hamstring injuries, which are 2.5 times more common than quadriceps injuries (Woods et al., 2004). Recent figures published by Ekstrand et al suggested that, in a professional male football team of 25 players, about 5 hamstring injuries occur each season, equivalent to more than 80 lost football days (Ekstrand et al., 2011). In terms of professional elite athletes, shortened recovery time could mean continuing with training, increased game play and benefit to the team and club. Therefore, further research is needed to analyse the new techniques in treating muscle injuries. In 2008, an article in the British Journal of Sports Medicine titled "The early management of muscle strains in the elite athlete: Best practice in the world with a limited evidence", summarised that currently almost all our socalled knowledge has a basis of level 4 or level 5 (Orchard et al., 2008a). The panel of experts continued to highlight the importance of Dr. Mueller- Wohlfahrt's injection treatment regimen for treating muscle injuries. In brief, the treatment protocol involves multiple local injections and associated back injections with a mixture of a homeopathic and pharmacological cocktail (Wohlfahrt, 2008). Therefore, the biochemical property, pharmacodynamics and pharmacokinetics of each drug are altered and unpredictable. The only potential “active” substance in Dr. Mueller-Wohlfahrt’s cocktail could be a drug called “Actovegin” which is a licenced clinically used drug with a track record of over 60 years. Therefore in this PhD thesis, in order to avoid the unpredictable nature of poly-pharmacy as discussed above, only Actovegin will be investigated. In order to investigate the potential therapeutic effect or efficacy of Actovegin on muscle injury, basic muscle structures, histology and pathophysiology of the healing process were discussed. The biochemical 10 events following skeletal muscle injuries and repair are driven by cytokines, monocytes and leukocytes. The speed and quality of muscle healing are dependent on the inflammatory process. In order to alter the speed or quality of muscle repair, Actovegin must be able to modulate the inflammatory process. The in-vitro study in this PhD thesis was the first study to investigate the role of Actovegin in the inflammatory process and demonstrated significant results. It confirmed that Actovegin could modulate the inflammatory process by influencing the CD68+ and CD163+ macrophages and CD163+ THP-1 cells, which could influence the muscle healing process. Based on the findings from the in vitro studies and data from previous literature, a stand-alone single drug intramuscular Actovegin injection therapy regimen was developed to treat acute muscle injuries. The first clinical study using this stand-alone Actovegin treatment regimen was conducted in this PhD in professional footballer players and translated the in vitro findings to clinical practice, which confirmed that Actovegin could influence clinical outcome in treating acute muscle injuries. This thesis summarises the current evidence on Actovegin. Compared with conventional conservative RICE and NSAID therapy, Actovegin proposes an exciting and legal alternative for high performance athletes. From the studies, Actovegin injection therapy seems safe and well tolerated. Overall, this PhD has suggested that Actovegin has an active role in the treatment of muscle strain injuries biochemically and clinically.