Physical Therapy in the Treatment of Venous Leg Ulcers: Biophysical Mechanisms

  Abstract: The present study sought to estimate the hemodynamic effects inside wounds after applying infrared thermography. Clinical results were analyzed to evaluate any correspondence with hemodynamic events occurring inside the wounds. Methods. Group 1 consisted of 20 patients with venous leg ulcers (12 women, 8 men). Patients from group 1 received 1 high-voltage stimulation (HVS) procedure. Group 2 consisted of 23 patients (16 women, 7 men). Patients from group 2 received 1 ultrasound (US) procedure. Group 3 consisted of 21 patients (13 women, 8 men). Patients from group 3 received 1 low-level laser therapy (LLLT) procedure. Group 4 consisted of 23 patients (15 women, 8 men). Patients from group 4 received 1 compression therapy (CT) procedure. Group 5 consisted of 19 patients (11 women, 8 men). Patients from group 5 received 1 quasi-CT procedure. Infrared thermography was used to monitor arterial hemodynamic effects for each ulcer. Infrared thermography, based on analysis of wound surface temperatures, was used to reflect normal or abnormal arterial circulation in capillaries. The average and maximal temperatures before and after each physical procedure were measured 5, 10, 15, and 30 minutes afterward. Results. The application of HVS and LLLT did not change the temperature inside the wounds. A significant temperature increase was noted after application of US and CT. The quasi-CT induced a thermal effect (only for a few minutes), but was not as intense as the effect of the compression stockings. The measurements showed a prolonged and steady thermal effect. Conclusion. The hemodynamic effect (improvement of arterial microcirculation inside the venous leg ulcer) is one of the most significant biophysical mechanisms of healing after clinically efficient compression therapy. Hemodynamic reactions are not basic mechanisms of high voltage stimulation and ultrasound therapy during the healing of venous leg ulcers. Computed thermography is a simple and useful tool to measure hemodynamic effects in wound healing.

Introduction

  Management of venous leg ulcers should be based on understanding pathophysiologic abnormalities. The pathophysiology of venous ulceration is controversial¹; however, it is believed that these ulcers result from venous occlusion or valvular incompetence and subsequent superficial venous hypertension. Venous leg ulcers occur as a result of underlying venous disease where damage has occurred to the superficial, deep, or perforating veins. Although the etiology of venous ulceration is unclear, it has been suggested that ulceration results from increased intraluminar pressure in the capillaries, which results in fibrin deposition around the capillaries. White blood cells are activated and release proteolytic enzymes that cause further tissue destruction. The alternative “trap” hypothesis proposes that fibrin and macromolecules eventually leak into the dermis where they bind with growth factors, making them unavailable to the tissue repair process.   More recent theories have associated the pathogenesis of venous ulcers with microcirculatory abnormalities. Physical therapies improve arterial blood circulation inside the wound^2–4 by reaching capillaries near the surface, which transports heat via blood flow into deeper layers and increases capillary blood flow near the surface of the skin, while expanding the blood flow areas. Better blood microcirculation produces a therapeutically usable field of heat within the tissue and accelerates the healing process.   Based on the results of a clinical study,⁵ the authors concluded that compression therapy (CT) is the most effective physical method in venous leg ulcer healing. High voltage stimulation (HVS) and ultrasound therapy (US) are useful only in patients who are treated conservatively. The authors also concluded that laser therapy (LLLT) is not helpful in the treatment of venous leg ulcers.   The present study sought to estimate the hemodynamic effects inside venous leg ulcers using infrared thermography. Clinical results were analyzed to determine any correspondence with hemodynamic events inside the wound.

Methods

  The experimental protocol was approved by the local Bioethics Commission. All participating subjects provided both written and oral consent to participate in the study.   The study was conducted between 2006 and 2008 among 106 patients with venous leg ulcers who were treated in the General, Vascular, and Transplant Surgery Department at the Medical University of Silesia (Katowice, Poland). The patients were allocated into 5 comparative groups (Figure 1).   Group 1 consisted of 20 patients (12 women, 8 men). The average age was 61.81 years (41–75 years). The average weight was 70.92 kg (51 kg–90 kg). The average height was 165.61 cm (161 cm–182 cm). The average initial wound surface area was 24.89 cm² (4.10 cm²–33.64 cm²). The average ulcer chronicity was 34.04 months (4–72 months). In this group, 4 patients smoked cigarettes and 5 were obese. Patients in group 1 received 1 HVS procedure.   Group 2 consisted of 23 patients (16 women, 7 men). The average age was 62.20 years (47–80 years). The average weight was 74.52 kg (56 kg–91 kg). The average height was 170 cm (162 cm–188 cm). The average initial wound surface area was 26.01 cm² (4.54 cm²–48.60 cm²). The average ulcer chronicity was 35.08 months (3–96 months). In this group, 5 patients smoked cigarettes and 5 were obese. Patients in group 2 received 1 US procedure.   Group 3 consisted of 21 patients (13 women, 8 men). The average age was 61.60 years (44–78 years). The average weight was 72.88 kg (55 kg–90 kg). The average height was 165.65 cm (158 cm–182 cm). The average initial wound surface area was 23.78 cm² (4.44 cm²–34.71 cm²). The average ulcer chronicity was 34.04 months (6–74 months). In this group, 5 patients smoked cigarettes and 4 were obese. Patients in group 3 received 1 LLLT procedure.   Group 4 consisted of 23 patients (15 women, 8 men). The average age was 61.47 years (43–80 years). The average weight was 72.87 kg (57 kg–104 kg). The average height was 166.61 cm (156 cm–182 cm). The average initial wound surface area was 23.78 cm² (4.44 cm²–34.71 cm²). The average ulcer chronicity was 32.12 months (12–120 months). In this group, 6 patients smoked cigarettes and 4 were obese. Patients in group 4 received 1 CT procedure.   Group 5 consisted of 19 patients (11 women, 8 men). The average age was 60.73 years (43–79 years). The average weight was 76.17 kg (58 kg–98 kg). The average height was 168.18 cm (161 cm–189 cm). The average initial wound surface area was 27.01 cm² (3.81 cm²–34.22 cm²). The average ulcer chronicity was 33.21 months (6–96 months). In this group, 4 patients smoked cigarettes and 5 were obese. Patients in group 5 received 1 quasi-CT procedure.   All patients were evaluated using the Clinical, Etiologic, Anatomic, Pathophysiologic (CEAP) classification for chronic venous insufficiency (Table 1). Patients from all comparative groups received a single physical therapy procedure.   For HVS in group 1, a constant current generator was used (Ionoson, Physiomed Electromedizin AG, Germany). Double peak, monophasic impulses of 100 µs and a frequency of 100 Hz were applied. The voltage was set at 100. Stimulation was performed with a current that produced no motion effects, only a tingling sensation. Electrodes were made of conductive carbon rubber. The active electrode (cathode) size was matched to wound size, and placed on saline soaked gauze directly on the wound. The passive electrode (anode) was positioned above the knee joint, on the frontal surface of the patient’s thigh. The duration of procedure was 50 minutes (Figure 2).   Patients in group 2 received the US procedure. A Sonicator 730 apparatus (Mettler Electronics Corp, Anaheim, CA) was used to generate the acoustic beam. The power density was 0.5 W/cm² (spatial average, temporal average). A pulsed wave with a duty cycle of 1/5 (impulse time = 2 ms, interval = 8 ms) set at 1 MHz frequency was used. The procedures were performed in a water bath with a temperature of 34˚C. The ultrasound probe had an area of 10 cm² and was placed 2 cm above the wound. The duration of a single procedure was dependent upon the ulcer size—1 minute for each 1 cm² of ulcer area (Figure 3).   For LLLT in group 3, a 810 nm semiconductor GaAlAs laser (CTL-1106MX, Elektronika i Elektromedycyna sp., Poland) emitting a continuous wave was used. The laser head contained a single diode (High Power Devices, Inc, North Brunswick, NJ). The cross section of the beam emitted from the head was rectangular in shape (2 mm x 5 mm, or 10 mm²). The laser was wired to a CTL-1202S scanner (Elektronika i Elektromedycyna sp., Poland). The laser beam scanned the surface at the following frequencies: in the ordinate axis at a frequency of 20 Hz, and in the abscissa axis at a frequency of 0.5 Hz. The average output of the radiation was 65 mW. The output power was checked every week with a Mentor MA10 apparatus (ITAM, Zabrze, Poland). The scanning frequency was set at 0.5 Hz. The scanner was placed 50 cm from the ulcer surface. The duration of a single procedure was relative to wound size, and was adjusted in order to obtain an average dose of 4 J/cm² (Figure 4).   Patients in group 4 received medical compression stockings (Sigvaris 702, Gianzoni & Cie AG, Switzerland) providing 25 mmHg–32 mmHg of pressure at the ankle. The stockings were placed on the leg at the outpatient clinic in the morning and were worn the entire day (about 10–12 hours). The stockings were taken off at night.   In group 5, common stockings (noncompression) were used for quasi-CT. The stockings were placed on the leg, applying the same methodology as in group 4. Quasi-CT was employed in order to estimate the role of convection and evaporation streams.   The MobIR 3 (Wuhan Guide Infrared Technology, China) infrared camera was used in this study, and is an uncooled long wave detector UFPA (third generation uncooled micro bolometer sensor 8 µm–14 µm) with a thermal sensitivity of 80 mK. The infrared camera was connected to a portable computer through a special interface. All images were stored on the computer for further analysis (Figure 5). Image analysis was performed with Guide IrAnalyser V1.4 researcher software (Test-Therm, Poland). Infrared thermography was used to monitor the arterial hemodynamic effects on each ulcer. Infrared thermography was based on analysis of wound surface temperatures. The reaction is a result of normal or abnormal arterial circulation in capillaries. The measurements were conducted in 24˚C. The distance from camera to the ulcer remained constant (120 cm). The average and maximal temperatures immediately before and after each physical therapy procedure, and then 5, 10, 15, 30 minutes later, were measured. The percentage of error for assessments was 2%.

Statistical Analysis

  Analysis of variance (ANOVA) for countable variables, and chi-square test for quality variables were used to compare individual parameters that characterized the study groups. Comparisons of thermal effects among groups were estimated based upon ANOVA and Tukey’s post hoc test (P < 0.05).

Results

  The groups were matched for age, weight, height, sex, ulcer location, ulcer chronicity, ulcer size, CEAP classification, and number of smokers (Table 1; P > 0.05).   The application of HVS (group 1) and LLLT (group 3) did not change the temperature inside the wounds (Tables 2, 3). A significant increase in temperatures was noted after application of UD and CT. Quasi-CT induced the thermal effect (only for a few minutes), but was not as intense as actual medical compression stockings.   In group 2, initial temperatures increased from 30.56˚C to 32.75˚C (P = 0.006), and to 31.09˚C (P = 0.03) at 5 minutes after the UD procedure ended. The maximal temperature increased from 31.89˚C before the procedure to 33.67˚C after the procedure (P = 0.006), and to 32.13˚C (P = 0.04) 5 minutes after the procedure ended. The thermal effect was brief, because measurements after 10, 15, and 30 minutes were comparable with initial measurements (P > 0.05).   In group 4, initial temperatures increased from 30.21˚C to 32.66˚C (P = 0.006), and to 32.29˚C (P = 0.03) 5 minutes after, 32.09˚C (P = 0.01) 10 minutes after, 31.78˚C (P = 0.03) 15 minutes after, and to 31.49˚C (P = 0.03) 30 minutes after the CT procedure. The maximal temperature increased from 32.24˚C before to 34.09˚C after the procedure (P = 0.006), 34.01˚C (P = 0.006) 5 minutes after, 33.56˚C (P = 0.01) 10 minutes after, 33.33˚C (P = 0.03) 15 minutes after, and 33.26˚C (P = 0.03) after 30 minutes. The measurements revealed a long and steady thermal effect when using compression stockings.   In group 5, initial temperatures increased from 30.44˚C to 31.12˚C (P = 0.03) after 1 quasi-CT procedure. The maximal temperature increased from 32.01˚C to 32.64˚C after treatment (P = 0.04). The thermal effect after quasi-CT was very brief; after 5 minutes the temperatures decreased to their initial values (P > 0.05).

Discussion

  Traditionally, evaluation of skin temperature has been studied using systems involving 1 or more single point measurements, such as with thermocouples. It is only since the availability of infrared imagers that efficient, noncontact temperature recording has become possible. In a fraction of a second, a large area of the human body can be imaged with a thermal resolution approaching 50 mK, as well as a spatial resolution of 25 µm–50 µm.⁶   Infrared imaging also simplifies documenting dynamic responses to stimuli.^7,8 Thirty years of clinical use and hundreds of peer-reviewed studies in the medical literature have established that thermography is a safe and effective means to examine the human body.   Today, infrared thermal imaging has become one of the most efficient techniques for evaluating skin temperature. Modern infrared digital cameras, employing advanced focal-plane array technology, provide a sensitive diagnostic tool for a multitude of clinical situations, ranging from breast cancer screening to open heart surgery.   The present study is the first clinical experiment to use infrared imaging to assess the thermal effect, as a result of increased blood flow in the ulceration, after physical therapy treatments. Only 1 other study in the literature has measured thermal effect as a hemodynamic reaction inside venous leg ulcers.² In their opinion, thermography from the video sequences is a clear indication of the extent of skin heating during treatment. In larger, deeper ulcers, there is a characteristic warm area along the ulcer rim, which is presumably due to increased blood flow of the tissue in this area.   The CT is thought to restore valvular competence and reduce or suppress superficial and deep venous reflux. There are various methods of CT, including specialized compression stockings, elastic and inelastic compression bandages, and intermittent pneumatic compression systems. Blood flow will vary greatly according to the compression system applied and types of materials used. The precise mode of action of compression is not fully understood, but numerous perceived benefits have been proposed,^9–11 including decrease in edema, softening of lipodermatosclerosis, acceleration of venous flow back toward the heart, decrease in venous volume, reduction in venous reflux, and improvement in lymph drainage.   Partsch et al¹¹ investigated the decrease of venous filling index (VFI) after various methods of CT. In their study, the initial values of VFI without compression were in the pathological range (median 8.45 mL/sec), and were consistent with massive refluxes in all cases. The short-stretch bandage applied with a pressure of 20 mmHg diminished VFI to a median of 3.25 mL/sec, while the elastic bandage approached 4.25 mL/sec with a pressure of 40 mmHg. At 40 mmHg, this nonelastic bandage produced values that are nearly normal (2.2 mL/sec), and a further increase of compression pressure to 60 mmHg provided relatively minimal improvement (1.3 mL/sec). The elastic bandage had to be applied with 60 mmHg to obtain normal values (2.0 mL/sec).   The present findings show that one biophysical mechanism of CT is improvement of arterial blood circulation inside the wound with the use of medical compression stockings that provide pressure 25 mmHg–32 mmHg at the ankle (eg, in venous leg ulcer therapy, capillaries near the surface transport heat via blood flow into deeper layers, and increased capillary blood flow near the surface of the skin expands blood flow areas). Better blood microcirculation produces a therapeutically usable field of heat in the tissue and accelerates the healing process. Based on the results of a previous clinical study,⁵ the authors concluded that CT is the most effective physical method in venous leg ulcer healing. The clinical results strongly correspond with results obtained regarding hemodynamic events inside the wound.   The authors maintain that the biophysical mechanisms of wound healing after HVS are: enhanced local blood circulation, increased proliferation of capillaries, and lymphatic vessels, as well as increased production of DNA, and collagen and fibroblast proliferation.¹²   The present results did not confirm that improved blood flow in the wound is a significant mechanism after application of HVS. Theoretical interpretation of the effects of HVS is a complicated issue. One phenomenon contributing to the explanation of wound healing is the so-called “skin battery.” The sodium pump drives the “skin battery.” The surface between the positively charged wound surface and the negatively charged undamaged skin surrounding the wound generates an electrical current that travels through the tissues in the moist wound environment. This is a precondition for proper tissue reconstruction. Absence or reduction of the potential difference may delay the regenerative process. By stimulating the wound with the positive pole, the potential difference may be increased or restored, thus restimulating the healing process.⁴ Further research is needed, in the authors’ opinion.   The biophysical effects of ultrasound are traditionally separated into thermal and nonthermal effects (cavitation, acoustic streaming). Changes in blood flow due to heating at clinically acceptable doses are probably confined to the skin.   In a study using duplex ultrasound scans (with the option of gray-scale or Doppler mode) to measure saphenous vein cross-sectional area, heat stress (via a thermal suit perfused with water at 49˚C) resulted in doubling of the cross-sectional area, and therefore blood volume, in this vein. An increase in blood flow facilitated rapid turnover of warm blood, which assisted cooling.¹³   In muscle, the use of radioactive tracers in human subjects showed that heating agents, including ultrasound, do not cause an increase in blood flow that is comparable to that caused by even moderate exercise.¹³ This finding was confirmed recently using venous occlusion plethysmography and laser Doppler flowmetry before and after the administration of continuous ultrasound (1.5 W/cm² for 5 minutes). A reasonable explanation for the discrepancy between these studies and studies demonstrating that muscle blood flow increased with heating is that the latter studies used only plethysmography to measure blood flow. This technique, however, does not measure tissue-specific changes in blood flow in tissues, such as muscle.¹³   Robinson and Buono¹⁴ noted that researchers using the Xenon-33 washout technique to measure muscle blood flow concluded that continuous ultrasound at an intensity of 1.5 W/cm² applied for 5 minutes to the forearm did not increase blood flow. It is possible, however, that ultrasound at higher intensities may increase muscle blood flow. For example, although no increase in muscle blood flow was found at tolerable ultrasound intensities, increased muscle blood flow did occur at intolerable ultrasound intensities (high intensity continuous ultrasound is intolerable due to pain caused by excessive heating). The contention that high temperatures are necessary to increase muscle blood flow is supported by a study that used microwave heating to achieve temperatures in excess of 44.5˚C. Muscle blood flow increased from a pretreatment value of 10 mL/min/100 g to 44 mL/min/100 g. However, this increase was far less than the increase from 2 to 4 mL/min/100 g at rest to 80 mL/min/100 g of muscle achieved with extreme exercise. Moreover, this increase is not achievable in a clinical setting due to the intolerably high intensity of ultrasound that is required.   The present results did not confirm that improved blood flow in the wound is a significant mechanism after application of ultrasound. The thermal effect was significant, but extremely short. The events were not connected with a hemodynamic effect inside the wound.   It has been reported that LLLT can accelerate wound healing. These findings are supported by in vitro examinations confirming that low-level laser irradiation significantly increases cell proliferation and collagen deposition.^15–17 Based on the results of a clinical study,⁵ the authors concluded that LLLT is not an effective physical therapy method for treating venous leg ulcers. Improvement of arterial blood circulation inside the wound was not observed.

Conclusion

  The present findings suggest that the hemodynamic effect (improvement of arterial microcirculation inside the venous leg ulcer) is one of the most significant biophysical mechanisms of healing after clinically efficient compression therapy. Hemodynamic reactions are not basic mechanisms of high voltage stimulation or ultrasound therapy during the healing of venous leg ulcers. Computed thermography is a simple and useful tool for measuring hemodynamic effects in wound healing.

References

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