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shock waves (Speed 2013). RPWs are capable of treating a larger area than focused extracorporeal shock waves, making it less necessary to use ultrasound or other imaging techniques to guide the exact location of therapy (Loske 2017). However, RPWs are not true shockwaves. Due to this and their superficial nature, RPW therapy (RPWT) may not be as effective in treating focal, deeper musculoskeletal pathologies in the horse. Table 1 provides a brief comparison of different types of ESWT and RPWT machines. The energy transmitted per unit pulse in a shockwave
treatment is termed the energy flux density (EFD) and is expressed in mJ/mm2 (Loske 2017). Focused shockwave sources generate a high EFD at the target tissue, whereas radial pressure wave sources generate a lower EFD at the target tissue (Loske 2017). What truly defines EFD as low, medium or high varies widely between authors and no standard has been set. The highest energy deposition and greatest biological effects of shock waves are achieved in anatomical regions with differing tissue mediums, such as a bone-soft tissue interface (Ogden et al. 2001). The total energy applied to the tissue is equal to the number of pulses multiplied by the energy per pulse (Ogden et al. 2001).
Review of molecular changes
Changes to the molecular composition of tendons and ligaments by ESWT have been studied in man and animals. A recent in vivo study demonstrated that radial ESWT used on human Achilles tendons promoted proinflammatory and catabolic processes, which are associated with removing damaged tendon matrix after injury (Waugh et al. 2015). An in vitro study evaluated rat tenocytes after treatment with two ESWT energy levels (0.36 mJ/mm2 and 0.68 mJ/mm2) and each level was used for 50, 100, 250 and 500 shockwaves, respectively (Chao et al. 2008). This study showed a dose-dependent decrease in cell viability immediately after shockwave in the groups receiving the highest EFD, vs. positive stimulatory effects in cell viability in groups treated with lower EFD. In addition, shockwave stimulation at 0.36 mJ/ mm2 significantly increased collagen synthesis by tenocytes (Chao et al. 2008), indicating that using substantially higher ESWT energy levels may be detrimental to some tissues. One study in ponies used a focused ESWT source with an EFD of 0.14 mJ/mm2 to show a stimulating effect on tenocyte metabolism, characterised by an increased synthesis of glycosaminoglycan (GAG) and total protein 3 h following
TABLE 1: Examples of focused shock wave (SW) and radial pressure wave (RPW) systems available to practitioners (this is not an inclusive list)
SW or RPW
Focused SW – electromagnetic Focused SW – electrohydraulic
Focused SW – piezoelectric RPW
Machine Storz Duolith Vet1
PulseVet VersaTron2 Equitron2 NeoVet3
Wolf Piezoson4
Swiss Dolorclast5 Storz Duolith Vet1 Storz Masterpuls MP50 Vet1 Storz Masterpuls MP100 Vet1 Storz Masterpuls MP200 Vet1
ESWT (Bosch et al. 2007). Collagenase-induced suspensory ligament lesions in horses were treated with three treatments of focused ESWT with an EFD of 0.15 mJ/mm2 and a total of 1500 shocks per treatment. This study showed an increase in the number of small collagen fibrils in treated limbs and increased expression of transforming growth factor b1
(TGF-b1), which enhances fibroblast synthesis of collagen, fibronectin and glycosaminoglycan (Caminoto et al. 2005). These findings should be kept in mind when performing shockwave therapy, and the practitioner should be aware of the maximum energy setting of the machine in use. In addition to tendon and ligament injuries, effects of
ESWT have also been studied on injured muscle. Zissler et al. (2016) used a rat model to study the effects of a single dose of ESWT on cardiotoxin-induced muscle injury. ESWT was applied only one day after the muscle injury was induced, and muscle was harvested and evaluated at Days 4 and 7 post-injury. Results showed that ESWT increased the growth rate of regenerating muscle fibres, increased number of nuclei in muscle fibres, and increased proliferation and differentiation rates of treated cells (Zissler et al. 2016). Extracorporeal shockwave therapy was also shown to
increase angiogenesis when applied to the Achilles tendon (near the tendon–bone junction) in rabbits. The rabbits were treated with a single shockwave treatment and the formation of neovessels was noted initially 4 weeks after treatment and persisted for at least 12 weeks (Wang et al. 2003). A similar study in dogs showed an increase in new capillary formation at 4 weeks after a single shockwave treatment to the Achilles tendon–bone junction (Wang et al. 2002). Ha et al. (2013) showed that shockwave energy levels between 0.9 mJ/mm2 and 0.16 mJ/mm2 directed at endothelial cells in vitro could cause cell apoptosis and death. However, this same study used lower energy levels (0.045 mJ/mm2) in vitro and in vivo to show that shockwaves activate expression of angiogenic genes via mechanosensory complexes, indicating that lower EFD may be more beneficial for angiogenesis than higher EFD treatments. Similarly, in rats with experimentally-induced spinal cord injury that were treated with low-energy ESWT, an increase in VEGF protein expression (a protein associated with angiogenesis) was found in affected neural cells, again indicating a potential beneficial use for ESWT to increase angiogenesis (Yahata et al. 2016).
ESWT and biological therapies
The possibility of a symbiotic relationship between biological therapies and shockwaves has clinicians wanting to perform both therapies simultaneously. Currently, few studies have evaluated the use of ESWT with concurrent stem cell therapy for treatment of tendon or ligament injuries in horses. Using ESWT-treated equine adipose-derived mesenchymal stem cells (ASCs) ex vivo, Raabe et al. (2013) showed that ASCs treated with ESWT had a higher proliferation rate and increase in kinases involved in cell growth and differentiation, and increased expression of cell-cell contact proteins. However, the study did show that excessive doses of ESWT could lead to increased cell damage and even cell death (Raabe et al. 2013). There are several human studies investigating the use of ESWT with concurrent stem cell therapy. ASCs treated with unfocused, low energy (0.09 mJ/ mm2) ESWT in vitro, were able to maintain capacity for both adipogenic and osteogenic differentiation (Schuh et al.
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