Ultrasonographic Evaluation of Extracorporeal Shock Wave Therapy on Collagenase-Induced Superficial Digital Flexor Tendonitis

Extracorporeal shock wave therapy decreased the percent lesion at the maximum injury zone compared with controls.

1. Introduction

Injuries involving the superficial digital flexor tendon (SDFT) are common in performance horses of many disciplines. These lesions require considerable periods of rest to allow healing, often re-occur when the horse goes back into full work, and in many instances, never heal adequately to allow return to the previous level of competition. Many treatment modalities have been used to facilitate healing of these lesions, but there are currently no treatments that stimulate healing to proceed in a timely manner on a consistent basis. The methods that have been employed include prolonged periods of inactivity, controlled exercise programs, anti-inflammatory therapy, intra-lesional injections, peri-tendinous injection of counter-irritants, sclerosing agents, tendon splitting, annular ligament desmotomy, superior check ligament desmotomy, and numerous other therapies [1,2]. As one would suspect by the number of therapies that have been tried, none promote healing in a timely fashion to allow earlier return to normal function. Long convalescence seems to be the most effective treatment, but even with it, there is a high rate of re-occurrence when the horse returns to its normal workload. The goal of treatment with extracorporeal shock wave therapy (ESWT) is not just to get horses back to work sooner but to promote a greater degree of healing to more closely approximate pre-injury collagen alignment of the tendon.

Extracorporeal shock waves are pressure waves generated outside the body that can be focused at a specific site within the body. Shock waves are characterized by high positive pressures, up to 80 MPa, and negative pressures of 5 - 10 MPa [3]. They have a rapid rise time of 30 - 120 ns and a short, 5-μs pulse duration [3]. They are differentiated from ultrasound waves by a lower frequency, minimal tissue absorption, and no thermal effects. The pressure waves travel through fluid and soft tissue, and their effects occur at sites where there is a change in impedance, such as the bone-soft tissue interface. The common use for shock wave therapy is to break up renal and ureteral uroliths into fragments that can be passed [3,4].

When the shock wave meets an interface of different impedance, pressure and shear loads develop [3]. Additionally, cavitation, which is the development of gas bubbles as a result of the rapid interaction between pressure and shear, occurs [3]. The collapse of the gas bubbles leads to the development of fast flow or jet streams, which contribute to the effect on tissue. In addition to these mechanical effects, there are also cellular effects. Shock waves can increase cellular permeability, stimulate cellular division, and stimulate cytokine production by cells [5,6]. However, at this time, the mechanism or mechanisms that shock waves use to stimulate healing in vivo is unknown.

Shock waves are now routinely used to treat common orthopedic conditions in humans, including plantar calcaneal spurs (heel spurs), epicondylopathic humeri radialis (tennis elbow), and non-union fractures [7]. The Food and Drug Administration has approved ESWT for the treatment of heel spurs in the United States.

Recent studies have shown that shock waves induce neovascularization at the tendon-bone junction, which in turn relieves pain and improves tissue regeneration and repair [8]. ESWT was also found to have a positive effect on the concentration of transforming growth factor beta-1, which has a chemotactic and mitogenic effect on osteoblastic cells [5]. In Europe and the United States, shock wave technology is being used for the treatment of equine musculoskeletal diseases. ESWT is a minimally invasive, safe method of treatment that would seem scientifically beneficial in cases of tendonitis.

The goal of this project was to use the collagenase model to induce lesions and to assess the healing characteristics of the lesions treated with ESWT versus untreated lesions to gain insight to the healing properties afforded by the use of ESWT. The reason for the experiment was to determine if ESWT is a viable treatment option for this type of lesion and whether it will shorten convalescent time and improve quality of healing of SDFT lesions.

2. Materials and Methods

Six sound mature horses with a mean age of 7.17 yr (range, 3 - 18 yr) and a mean weight of 470.53 kg (range, 411.36 - 510 kg) with ultrasonographically normal superficial digital flexor tendons were used for this study. Tendons were considered ultrasonographically normal if there was no disruption of the echogenicity and fiber alignment and their cross-sectional area did not exceed 1.2 cm2 [9]. The SDF tendon was ultrasonographically evaluated every 2 cm from 2 cm distal to the accessory carpal bone (CMDACB) to 24 CMDACB. A focal tendonitis of both front legs was induced in the center of the SDFT at 10 and 12 CMDACB. A 26-gauge needle was inserted into the tendon with ultrasonographic guidance to confirm needle placement, and 1000 IU of collagenase [a] was injected in each tendon to create the lesions. The horses received phenylbutazone as needed to control any discomfort after the procedure. Horses were maintained in a stall for the first week after collagenase injection. For the remainder of the project, they were allowed 2 h of turnout daily in a small paddock.

An ultrasound exam was performed on day 7 after injection and weekly thereafter through day 98. Transverse section images were obtained every 2 cm from 2 to 24 CMDAC, and longitudinal images were obtained at 4-cm intervals starting 2 CMDACB. The images were digitally captured, and an image analysis system [b,c,d] was used to measure the (1) percent lesion at the maximum injury zone (MIZ), (2) the gray scale of the SDFT at the MIZ in the cross-sectional image and, (3) the percent disruption of the fibers at the MIZ in the longitudinal image. The data were also summed for each of the 12 2-cm increments from 2 to 24 CMDACB to determine the (1) sum percent lesions, (2) sum gray scale, and (3) sum percent disrupted longitudinal fibers.

The lesions were allowed to mature for 31 days before the first ESWT was performed. The second and third treatments were given on 49 and 70 days, respectively, after induction of the lesions. Each ESWT was performed on the standing sedated horse with 1500 pulses at 0.14 mJ/mm2 using a focused shock wave generator [e] at the site of the lesion in one randomly assigned forelimb, and the other forelimb was used as an untreated control. The ultrasonographer was blinded as to the treatment and control groups.

Statistical analysis was performed on the outcome variables. Each variable was measured before the initial treatment and repeated at 3-wk intervals; therefore, the data are repeated measures. The analyses for the continuous data were multivariate analysis of variance (ANOVA) to accommodate the repeated measures. The assumption of sphericity for repeated measures ANOVA was not satisfied. First, the time by group interaction was checked to verify that the groups (treatment and control) maintained the same relationship over time, and the main effect (group) was checked for significance. Treatment and control outcomes were not statistically correlated pre-treatment or post-treatment, and horse effect was not included in the model. A final post-hoc ANOVA was done to test group difference between days 21 and 98. Significance was set at 0.05.

3. Results

There were no significant group by time interactions for any of the three variables (percent lesion, gray scale, percent fiber disruption) at the MIZ or the sums of each variable. The post-hoc ANOVA showed a significant (p = 0.02) group interaction, with a decrease in percent lesion at the MIZ (Figure 1).

Figure 1. The graph shows the changes in the percent lesion at the maximum injury zone as mean ± the SEM. At day 98, there was a significant difference between the treated and control tendons.

4. Discussion

The only significant finding was a small but significant decrease in percent lesion at the MIZ. The clinical significance of this difference is unknown. The difference was not found when the percent lesion was summed over the entire tendon, likely because it was diluted because of the multiple sites evaluated. We elected to evaluate the tendon at 12 sites at 2-cm intervals to provide a thorough investigation, even though most lesions were about 12 cm long from ~6 to 18 CMDACB.

Ultrasonography provides a mechanism to evaluate the tendon fibers non-invasively. Ultrasonograms can provide a mechanism to evaluate fiber alignment, but collagen type and tendon strength cannot be determined. Further evaluation of mechanical and histological effects of ESWT are indicated. We used the image analysis software for all of the variables to reduce the subjectivity associated with grading scales. The subjectivity of cursor placement remains when measuring the lesions, but the previously described fiber alignment score based on the estimation of longitudinal fiber alignment and the echogenicity scoring based on the density of the reflection from the lesion were replaced with direct measurements from the images.

ESWT is used to treat numerous tendon diseases in people. Compared with bone, tendons and ligaments are more at risk of damage from excess energy or number of pulses [10]. While the results of laboratory studies in rabbits cannot be directly extrapolated to horses, treatment with high energy equipment set at 0.89 mJ/mm2 resulted in increased inflammation in tendons and ligaments. Additionally, too few pulses or too little energy may not lead to the desired outcome. The energy (0.14 mJ/mm2) and number of pulses (1500) was based on clinical experience. Changing the energy or number of pulses may provide a greater improvement in healing.

Because it takes time for collagenase-induced lesions to stabilize, we could not initiate ESWT until the lesions were stable, which occurred between 21 and 28 days after injection. Clinically, it has been reported that early treatment of tendons with ESWT will help remove the initial fluid accumulation and improve the ultrasonograms faster than expected [11]. This study could not address the clinical report. The time interval between treatments and the total number of treatments administered could also have an effect on healing. These two variables were not accounted for in this study; the treatment regimen was based on previous clinical experience of one of the authors. With a collagenase model, the inflammatory reaction is the result of the digestion of collagen fibers rather than tearing as in the clinical situation. The model is a frequently used research tool; however, the results must be interpreted knowing the model may be different than clinical disease. Additional studies including the histologic and mechanical aspects of tendon healing after ESWT are indicated.

The authors thank HMT for providing the ESWT equipment.

Footnotes

1. Type 1-S, c1639; Sigma-Aldrich, St. Louis, MO 63103.
2. Pie Medical, Indianapolis, IN 46250.
3. Classic Metron-Lite, version 1.02; EponaTech, Creston, CA 93432.
4. Version 4.0.2; Scion Imaging, Frederick, MD 21701.
5. High Medical Technologies, Lengwil, Switzerland S-CH-8574.