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Electrical stimulation in wound healing
LITERATURE REVIEW
Electrical Stimulation in Wound Healing The authors present a review of the current literature regarding electrical stimulation with special focus on the merits of its uses in wound healing. Literature from a basic science, animal studies and clinical investigations are reviewed. The literature seems to suggest that electrical stimulation can effect wound healing, but the method of delivery remains uncertain. (The Journal of Foot & Ankle Surgery 36(6):457-461, 1997) Key words: ulcer, wound healing, electrical stimulation
John G. Fleischli, DPM, AACFAS 1 Terese J. Laughlin, DPM, AACFAS2 The use of electrical stimulation as adjunctive therapy for wound healing dates back to the 1700s when gold leafs were placed over open wounds to facilitate healing (1). The current literature presents various laboratory and clinical investigations of electrical stimulation as a wound treatment modality. Basic science investigations have primarily concentrated on cellular migration in the presence of an electric field, while animal investigations have concentrated on vascular supply, epithelialization, and wound healing. Most clinical studies in this area, however, are descriptive case series with ill-defined patient populations. There are also wide variations in the dose, frequency, and method of delivery of the electrical stimulation. A thorough review of the literature reveals anecdotal evidence for the use of electrical stimulation in wound healing, but strong scientific evidence has not been documented. The current review also demonstrates the need for further study in this area.
From the University of Texas Health Science Center at San Antonio, San Antonio, TX. t Assistant Instructor and Research Fellow, Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Address correspondence to: Foot & Ankle Associates of Jacksonville, 1515 W. Walnut, No.4, Jacksonville, Il 62650. 2 Chief Resident, Department of Orthopaedics, University of Texas Health Science Center at San Antonio, San Antonio, TX. The Journal of Foot & Ankle Surgery 1067-2516/97/3606-0457$4.00/0 Copyright © 1997 by the American College of Foot and Ankle Surgeons
Literature Review Basic Science
While the evaluation of electric stimulation at a basic science level can be a confusing process, it provides the necessary foundation for understanding its potential in the wound healing process. Several studies have evaluated the effect of in vitro cellular behavior when exposed to an electrical field. These investigations show that the application of an electric field can promote some important components of the wound healing process, including angiogenesis, fibroblastic proliferation, collagen synthesis, and epithelial cell migration (2-6). Ameia Yen-Patton found that when human and bovine vascular epithelial cells were exposed to an electromagnetic field, "sprouting" (an early stage of in vitro vascularization) could be increased up to 30 times that of controls. The amount of sprouting seen over a 5-hour period in an electrically stimulated sample would require 2 to 3 weeks in an unexposed sample. The authors concluded that pulsed electromagnetic fields might provide a mechanism to increase angiogenesis and augment healing (7). It has also been demonstrated that epidermal cells (keratocytes) and fibroblasts exposed to an electric field migrate toward the cathode (2, 5). Brown found that rabbit skin exposed to electrical stimulation demonstrated an epidermal layer that was on average twice as thick as controls (4). Additionally, it has been found that electrical stimulation increases collagen synthesis in both swine skin and human fibroblasts (3, 6). Not all VOLUME 36, NUMBER 6, 1997
457
authors, however, were successful in the duplication of these results. In an investigation using rats , Harrington et al. found that incisions treated with electrical stimulation demonstrated slower epidermal cell migration than wounds of the controls. The treatment group did however, demonstrate an increased development and organization of the dermal layer of skin with greater angiogenesis. This was attributed to the magnitude of the electric current. They felt that the higher magnitude affected cellular migration patterns rather than cellular proliferation patterns (8). These studies demonstrate that at the cellular level, the application of an electrical field can alter epithelialization, fibroblast migration, collagen synthesis, and angiogenesis; all are important components in wound healing . The antimicrobial effects of electrical stimulation have been investigated by several methods. The application of an extracellular electric field has produced a chemotactic effect on macrophages. The macrophages develop extensions of pseudopodia in the direct ion of the positive pole in much the same fashion as demonstrated by fibroblasts (9). Rowley et al. found that in vitro growth rates of Escherichiacoli and Pseudomonas aeruginosa were affected by exposure to an electric field (10). The authors noted that the application of a negative electrode to the wound site in a rabbit model served to suppress not only healing but also the infection process. In their treatment protocol, the negative electrode was kept over the wound until infection was no longer present clinically (11). Laboratory investigations of Staphylococcus aureus revealed that electrical fields can diminish growth in vitro (12). Anecdotal reports have claimed similar results in human studies (13). Wolcott et al. found a decrease in the number of pathogens cultured from 75 decubitus ulcerations treated with electrical stimulation. Unfortunately, no description of the means by which the cultures were obtained was given (14). Not all investigators have found an antimicrobial affect. Alvarez and coworkers failed to demonstrate any significant decrease in bacterial colony formation using a swine model. The investigation was limited in that the animals served as their own controls, and therefore, some residual effect of the previous treatment may have inhibited bacterial growth (3). Animal Studies
Studies using animals have demonstrated that electrical stimulation increases both perfusion and the healing rate of skin wounds (13-20) . To date, no correlation of these results to human subjects has been made (21). Unfortunately, these animal investigations demonstrate no consistency in study design and treatment methodology (3, 21-23). 458
THE JOURNAL OF FOOT & ANKLE SURGERY
Several authors speculate that changes seen with the use of electrical stimulation are attributable to an increase in tissue perfusion (16, 21, 24). Kjartansson et al., in an attempt to increase tissue perfusion, created a skin flap on the back of rats that was immediately sutured back in place. The animals then received different doses of electrical stimulation from transcutaneous electrical nerve stimulation (TENS) units. Animals treated multiple times with TENS had significantly better flap survival rates then those treated with only one stimulation. The authors theorized that electrical stimulation may improve flap survival through the release of vasodilatory neurotransmitters from small to medium sized sensory neurons, or through the activation of large diameter sensory nerves that could subsequently inhibit sympathetic vasoconstrictory neuron activity (22). Stimulation also seems to increase muscle perfusion (25-28). Myrhage and Hudlicka found increased capillary diameter and surface area in stimulated rat and rabbit musculature. They theorized this was the reason for the boost in blood flow during electrical stimulation (29). Animal models also demonstrated that cellular components of wound healing increase in the presence of an electrical field. In 1989, Cruz et al. found that electrical stimulation of bums in swine resulted in an increase in fibroblastic response, and thus faster rates of wound contracture. She also noted that at the conclusion of the 4-week investigation, 40% of the treatment group had healed wounds while none of the control animals had healed (30). Brown et al. also demonstrated an increased rate of epithelialization in 18 rabbits treated with high voltage stimulation (4). Clinical Studies
The investigations of electrical stimulation involving human subjects have primarily concentrated on wound healing, but have failed to show any consistent methodology (13-17, 24, 31, 32). Little uniformity exists in the literature with regards to duration, frequency, location of polarity, and other factors. The lack of operational definitions concerning patient selection further clouds the issue. It is interesting to note that several authors excluded patients with evidence of peripheral vascular disease, yet do not offer any description of the criteria used to define peripheral vascular disease (15, 24, 31). The lack of consistency in treatment methodology is troublesome in that it is difficult to arrive at any conclusion that is adaptable to patient use. Several authors felt that changes in polarity are important (13-15 , 17, 24, 33). Still other authors have developed specific time protocols for the application of electric stimulation [(13,16,17,24,31,33,34) Fig. 1]. A hyperemic response to electrical stimulation has been
AUTHOR _ _100 lH8 Wolcott It II
lH8
APPLICATIONTIME
DOSAGE
Not repco1ed.
SO- 100 ",", 0.2 - 0.5 v.
2 hours then 4 hours off three t:irneI 8 d a y . _ .... _ - 400-800 mIcrcMlporoo. heeling hu plot_.
NegatIve._
POLARITY
-_. -_. -_. ulcer.
Nogllllvo._ ovortho ulcer. Ctw1ge .. wound
2 hours on, 4 hours; seven days •
1878
_k.
200-1000 ,.A.
ulcer. Chongod o s _
NegatIve_ _ ovortho 2 hour atlmul8lion twice a day; 5 days COrleyend Wain_I a _ _ a 2-4 hour rocovory 300- 7OO,.A. Current rongod ""'" 30 • ulcer. Chongoos_ 1885 1101lAlan2· period. FInN"." 1888
30 _
twice dolly; 2 _
poat-
op. once a day; 5 days a
TENS: 7 pu_, 100 Hz, durotlonof 90 """,,1wtcoo_.
_,_1Not repco1ed.
PosItMt electrode • the
Kloth and FHdllr
4S _
lH8
_k.
Lundllberg lit .1
pu_, durotlon 2h.... tho __by8-10hourslater _ appIIod. Controlgroup 010.4 rna ond Irequency 0180 Hz _ on _ _ pIacabot'or 2 houn twice a -.oIty at _ _ _ whlchtlngllng ..,utionilfelt. day untlllrnprovwnent or 7 days.
Not reportad.
1 houroll8-10houn. T h e n _ StmuI8lion at 0.2 ..... ond frequencyof of . _ o s 101_ by 2 hours 90Hz.
Not reportad.
Froquencyoll05Hz, InInIpMH_of SO_ vobgaloo-175V. ~
1888
Kja .... nuon and Lu_rg 1880
....net.1 1880
FHd.,out 1881
LundaMrgatol 1882
_wave
~.
a day; no longer thon 90
hours _
_.
4- 8 MonophasIc pulaad oulTOlll_ a pulaad traalmento lor 7 days. Iroquency of 129 ppoampllluda 0135 mAo
20 minuta 1wtcoa day lor up 10 11
AIIem8tian conll8nt lquar&-WllVe pulses (pullo width 1.....) at intano~ poroothasIIa.
78 _
poIIonts_
RESULTS
WOUND
V....,._ ulconllk>n8
-
ulconllk>n8 (not
_(not _lOCI)
106 ulcera.
Report o f _ COOlI reporto oNof tho ulconl-.. repco1ed os <:OIl1lIOI01y healed in 7, 32 ond 42 days. 40% of thou_ _ complotoly.
NagatIvoat tho ulcer. Then changed as-.nd
progrouad
_in_group_ollgn_ _1n-,,_(1.5102.5_)In_1
Treatment group of 15:
I_u_ (not_,
Treatment group of 18;
Pook>p~ IU8 ond g _ 0 ' - higher Inaoue in ..... intho_group. (Symo's, BKA, 11<) _
canlroI 0133.
Treatment group 9: control group of 7.
Troatmenlgroup 0118: control group 0119.
Not repco1ed.
A. . . . hooIklg_ofU_intho_ 48 of tho _ _ complotoly_1Il oddlllonol 11 _ a ' * ' - in .... ofgrooterthlllts'll>.
canlroI 0115.
Treatment group of 12;
75Hz_Ill ImpulHwidUlof 1.3 mI.
30 mlnuta twice dally_
83 ulconl.
control group 018.
Single pullo _ourront~ a . . . . . - fIaId 0I2.8mT atolrequency of
87 poIIonts_
Treatment group of 14; canlroI group of 10.
twice a day undlllgnl of lId'lemla.
3-4 _ days.
Three cue reports .
doIInod)
NegatIve _ _ ovortho
Gault and G_na
POPULATION
ovortho
Treatment group of 28: control group of 24.
PoIor1ly changad -.. oach Treatment group of 32; control group 0132.
treatment.
-.._
Treatment group 11II_ by 7.3_, ata Stage IV decubltuo haaIIng _ 01_ per_ contnll group had ond _ in -.rid slleof29.9'll>. Pook>p
. . - in_
...-y
'ParftlX' _dopplar-.otor.
--
group had oIgn-.uy higher .. meuurod by tho
blood _ _ tho 8th _
Pook>p skin flap
Treatment group _
V....,._ u_
No IIgnIllcantdllleronce _ days.
Mull/plo(otaolo,
T_group _ a grooterd_ In"" at oach _1<1 moaouromontlor 4 weeki.
deoutlIIus,ourgIcal, traumatic)
Venousstull ulcllratlons
a slgnlllcant Incroa8e in _Immedlatoly ond at 2-8 days.
groupo ""'" 0-90
Two groupo _ _ s oIgnlllcantdllleronos In pon>entago of poIIontsheslad at 8 and 12 _1<1. IUooallgnlllcant dllloronce In docroaoo In ulcer"" _th.groupo.
Not reportad.
HIgh vobga galvanic__1atIon.
Not reportad.
ToIaIof 14 pat_ dlvldod into3_andono oontrolgroup.
Preuure 80nII 01 Graataol chango Inwound sIz..... in group naiad groal«then3_ wMh.-':ll1imulatlonoJono. durotlon
Alan at stl888
1 hour 3 days per_k.
Monophaolcpulaad HV alImulator oat at oontInuouomodo at puloo _ of 80 ppo.
PoaIlIveelectrodeover the ulcllratlon.
15 ambul8lory poIIonts;no oontn>I group.
0 _ foot
Bokor at stl997
1.5 hours dally.
Variable (asymmotrIc b1phao1c atlmul8lion). Pooltlvo_.dlslally.
Ake... and Oablalaon
1984
ulcanlllono
80 toIaI patIontoIn4 groupo: DIobatlc lag and including20 palIant oontn>I foot ulcerations group.
12 poIIonts_ In a moon period of 2.8 months. No IIgnll'lc8nt difference In the healing time or ulcer .... _ tho UOIof tho oIoc:trical alImulollon.
No oIgnlllcentdllloronce _
groupo.
FIGURE 1 A review of some of the literature using electrical stimulation as an adjunct therapy for wound healing. Little constancy is seen throughout.
suggested by several authors (35). Increased perfusion to the lower extremity by stimulation of the gastrocnemeous or spinal nerve roots have been achieved in test subjects (36, 37). Several authors reported accelerated healing of "ischemic ulcerations" with the use of electrical stimulation. These results are questionable, because the authors state that patients with peripheral vascular disease were excluded. No explanation of the criteria for exclusion or definition of ischemic ulcers was offered (15,35). Gault found that ischemic wound healing rates could be "doubled" with the use of electrical stimulation. Unfortunately, no analysis or description of wound selection was reported (33). Additionally, Baker et al., in a prospective study, found that diabetic wound healing could be accelerated with the use of electrical stimulation, but the operational definitions and methodology of this report are also suspect (35). Lundeberg et al. and Kjartansson et al. both investigated the use of external electrical stimulation as a means to combat ischemia of
skin flaps. They found a significant increase in the perfusion, as measured with a laser doppler flowmeter (18, 34). It is interesting to note that while both studies were conducted by the same authors, the method of delivering the electrical stimulation was different. Conclusion
There are a number of reports in the medical literature that suggest that the application of electrical current may enhance wound healing through proliferation and migration of both epithelial cells and connective tissue cells, which are pivotal components in the pathway of wound healing. Unfortunately, there is a lack of continuity of device and means of application, which make it difficult to apply these findings to patients. The literature is devoid of a sound investigation of electrical stimulation and its effect on the diabetic foot. Decreased local tissue perfusion and the resultant localized tissue hypoxia are contributing factors in many cases of diaVOLUME 36, NUMBER 6, 1997
459
betic neuropathic ulceration and resultant amputations (38). Once a wound has formed, there is an increased oxygen requirement to allow healing to occur (39). If the electrical stimulation device could help combat these factors, then ulcer healing times would be reduced and the risk of amputation diminished. It is clear that a well designed investigation is needed to aid in the development of criteria for treatment of all wound types. The diabetic wound, with its diverse pathological components, could benefit most from the advantages this therapy seems to offer. The potential increase in perfusion should be evaluated more thoroughly as a means of promoting soft tissue healing in high-risk diabetic patients. Carley and Wainapel point out that both the protocol and the bulky equipment need to be redesigned in an effort to allow ease of use and to increase their practical applications (13). To that end, the development of a dacron garment as described by Dimitrijevic might allow ease of application, and thus, ease of treatment (40).
21.
References
22.
1. Kanof, N. Gold leaf in treatment of cutaneous ulcers . J. Invest. Dermatology 43:441-442, 1964. 2. Cooper, M. S., Schliwa, M. El ectrical and ionic controls of tissue cell locomotion in DC electric fields. J. of Neurosci. Res . 13:223244, 1985. 3. Alvare z, O. M., Mertz, P. M., Smerbeck, R. V., Eaglstein, W. H . The healing of superficial skin wound s is stimulated by extern al electrical current. J. Invest. Dermatol. 81:144-148, 1983. 4. Brown, M., McDonnell, M. K., Menton, D. N. Polarity effects on wound healing using electric stimulation in rabbits. Arch . of Phys. Med . Rehabil. 70:624-627, 1989. 5. Erickson, C. A., Nuccitelli, R. Embryonic fibroblast motility and orientation can be influenced by physiological electric fields . J. Cell BioI. 98:296-307, 1984. 6. Bourguignon, G. J., Bourguignon , M., Bourguignon, L. Y. Effect of high voltage pulsed galvanic stimulation on human fibroblasts in cell culture-a model system of soft tissue healing. J. Am. Phys. Ther. Assoc. 1:9, 1986. 7. Arneia Yen-Patton, G. P., Patton, W. F ., Beer, D. M., Jacobson, B. S. Endothelial cell response to pulsed electromagnetic field: Stimulation of growth rate and angiogenesis in vitro. J. Cell . Physiol. 134:37-46, 1988. 8. Harrington, D . B., Meyer, R., Klein, R. M. Effects of small amounts of electric current at the cellular level. Ann. N. Y. Acad. Sci. 238:300-306, 1974. 9. Orida, N. Directional protrusive pseudopodial activity and motility in macrophages induced by extr acellular electric fields. Cell Motil . 2:243- 255, 1982. 10. Rowley, B. A. Electrical current effects on E. coli growth rates. Proc. Soc. Exp. BioI. Med . 139:929-934, 1972. 11. Rowley, B. A., McKenna, J. M., Chase, G. R. The influence of electrical current on an infecting microorganism in wounds. Ann. N. Y. Acad. Sci. 238:543-551, 1974. 12. Barranco, S. D., Spadaro, J. A., Berger, T . J., Becker, R. O.In Vitro effect of weak direct current on Staphylococcus aureus. Clin . Orthop. ReI. Res. 100:250-255, 1974. 13. Carley, P. J., Wainapal, S. F . Electrotherapy for acceleration of
460
THE JOURNAL OF FOOT & ANKLE SURGERY
14.
15.
16.
17. 18.
19.
20.
23. 24.
25.
26.
27. 28.
29.
30.
31.
32.
33. 34.
wound healing: Low intensity direct current. Arch . Phys. Med . Rehabil. 66:443-446, 1985. Wolcott, L. E., Wheeler, P. c, Hardwicke, H. M., Rowley, B. A. Accelerated healing of skin ulcers by electrotherapy: Preliminary clinical results. South. Med. J. 62:795-801, 1969. Feedar, J. A., Kloth, L. C., Gentzkow, G . D. Chronic dermal ulcer healing enhanced with monophasic pulsed electrical stimulation . Phys. Ther. 71:639-649, 1991. Finsen, V., Persen, L., Lovlien, M., Veslegaard, E. K., Simensen, M., Gasvann, A. K., Benum, P. Transcutaneous electr ical nerve stimulation after major amputation. J. Bone Joint Surg. 70B:109112, 1988. Kloth, L. C; Feedar, J. A. Acceleration of wound healing with high voltage, monophasic, pulsed current. Phys. Ther. 68:503-508 , 1968. Lundeberg, T., Kjartansson, J., Samuelsson, U. Effect of elec trical nerve stimulation on healing of ischaemic skin flaps. Lancet 24:712-714, 1988. U.S. Department of Health and Human Services PHS, Agency for Health Care Policy and Research. Pressure Ulcer Treatment, Quick Reference Guide for Clinicians. Vol. 15, AHCPR, Rockville , MD ,1994. Thurman, B. F., Christian, E . L. Response of a serious circulatory lesion to electrical stimulation. Phys. Ther. 51:1107-1110, 1971. Kjartansson, J., Lundeberg, T ., Samuelson, U. E. Transcutaneous electrical nerve stimulation (TENS) increases survival of ischaemic musculocutaneous flaps . Acta Physiol. Scand. 134:95-99, 1988. Kjartansson, J., Lundenberg, T., Samuelson, U. E., Dalsg aard , C. J., Heden, P. Calcitonin gene-related peptide (CG RP) and transcutaneous electrical nerve stimulation (TENS) musculocutaneous flap in the rat. Acta Physiol. Scand. 134:89-94, 1988. Im, M. J., Lee, W. P., Hoopes, J. E. Effects of electrical stimul ation on survival of skin flaps in pigs. Phys. Ther. 70:37-40, 1990. Lundeberg, T. C., Eriksson, S. Y., Malm, M. Electrical nerve stimulation improves healing of diabetic ulcers. Ann. Plast. Surg . 29:328- 331, 1991. Crayton, S. C., Aung-Din, R., Fixler, D . E., Mitchell, J. H. Distribution of cardiac output during induced isometric exercise in dogs. Am . J. Physiol. 236:H 218 - H 224, 1979. Folkow, B., Gaskell, P., Waaler, B. A. Blood flow through limb muscles during heavy rhythmic exercise. Acta Physiol. Scand. 80:61-72, 1970. Clement, D. L., Shepherd, J. T. Influence of muscle afferents on cutaneous and muscle vessels in the dog. Circ. Res. 35:177-183,1974. Clement, D. L., Pannier, J. L. Cardiac output distribution during induced static muscular contractions in the dog. Eur. J. Appl. Physiol. 45:199-207, 1980. Myrhage, R., Hudlicka, O . Capillary growth in chronically stimulated adult skeletal muscle as studied by intravital microscopy and histological methods in rabbits and rats. Microvasc. Res. 16:73-90, 1978. Cruz, N. 1., Bayron, F . E ., Suarez, A. J. Accelerated healing of full-thickness burns by the use of high-voltage pulsed galvan ic stimulation in the pig. Ann. Plast. Surg . 23:49-55, 1988. Ieran, M. Effect of low frequency pulsing electromagnetic fields on skin ulcers of venous origin in humans: A double-blind study. J. Orthop. Res . 8:276 -282, 1990. Akers, T. K., Gabrielson, A. L. The effect of high voltage galvanic stimulation on the rate of healing of decubitus ulcers. Biom ed. Sci. Instrum. 20:99-100, 1984. Gault, W. R. Use of low intensity direct current in management of ischemic skin ulcers . Phys. Ther. 56:256-269, 1976. Kjartansson, J., Lundeberg, T . Effects of electrical nerve stimulation (ENS) in ischemic tissue. Scand. J. of Plast. Reconstr. Surg. Hand Surg. 24:129-134, 1990.
35. Baker, L. L., Chambers, R., DeMuth, S. K., Villar, F. Effects of electrical stimulation on wound healing in patients with diabetic ulcers. Diabetes Care 20:405-412, 1997. 36. Currier, D. P. Electrical stimulation effect on localized blood (Abstract). Phys. Ther. 63:761, 1983. 37. Dooley, D. M., Kasprak, M. Modification of blood flow to the extremities by electrical stimulation of the nervous system. South. Med. J. 69:1309-1311, 1976.
38. Hauser, C. J., Klein, S. R., Mehringer, C., Appel, P., Shoemaker, W. C. Assessment of perfusion in the diabetic foot by regional transcutaneous oximetry. Diabetes 33:527-531, 1984. 39. La Van, F. B., Hunt, T. K. Oxygen and wound healing. Clin. Plast. Surg. 17:463-472, 1990. 40. Dimitrijevic, M. M. Mesh-Glove. A method for whole-hand electrical stimulation in upper motor neuron dysfunction. Scand. J. Rehabil. Med. 26:183-186, 1994.
VOLUME 36, NUMBER 6, 1997
461
Electrical Stimulation in Wound Healing The authors present a review of the current literature regarding electrical stimulation with special focus on the merits of its uses in wound healing. Literature from a basic science, animal studies and clinical investigations are reviewed. The literature seems to suggest that electrical stimulation can effect wound healing, but the method of delivery remains uncertain. (The Journal of Foot & Ankle Surgery 36(6):457-461, 1997) Key words: ulcer, wound healing, electrical stimulation
John G. Fleischli, DPM, AACFAS 1 Terese J. Laughlin, DPM, AACFAS2 The use of electrical stimulation as adjunctive therapy for wound healing dates back to the 1700s when gold leafs were placed over open wounds to facilitate healing (1). The current literature presents various laboratory and clinical investigations of electrical stimulation as a wound treatment modality. Basic science investigations have primarily concentrated on cellular migration in the presence of an electric field, while animal investigations have concentrated on vascular supply, epithelialization, and wound healing. Most clinical studies in this area, however, are descriptive case series with ill-defined patient populations. There are also wide variations in the dose, frequency, and method of delivery of the electrical stimulation. A thorough review of the literature reveals anecdotal evidence for the use of electrical stimulation in wound healing, but strong scientific evidence has not been documented. The current review also demonstrates the need for further study in this area.
From the University of Texas Health Science Center at San Antonio, San Antonio, TX. t Assistant Instructor and Research Fellow, Department of Orthopaedics, University of Texas Health Science Center at San Antonio, Address correspondence to: Foot & Ankle Associates of Jacksonville, 1515 W. Walnut, No.4, Jacksonville, Il 62650. 2 Chief Resident, Department of Orthopaedics, University of Texas Health Science Center at San Antonio, San Antonio, TX. The Journal of Foot & Ankle Surgery 1067-2516/97/3606-0457$4.00/0 Copyright © 1997 by the American College of Foot and Ankle Surgeons
Literature Review Basic Science
While the evaluation of electric stimulation at a basic science level can be a confusing process, it provides the necessary foundation for understanding its potential in the wound healing process. Several studies have evaluated the effect of in vitro cellular behavior when exposed to an electrical field. These investigations show that the application of an electric field can promote some important components of the wound healing process, including angiogenesis, fibroblastic proliferation, collagen synthesis, and epithelial cell migration (2-6). Ameia Yen-Patton found that when human and bovine vascular epithelial cells were exposed to an electromagnetic field, "sprouting" (an early stage of in vitro vascularization) could be increased up to 30 times that of controls. The amount of sprouting seen over a 5-hour period in an electrically stimulated sample would require 2 to 3 weeks in an unexposed sample. The authors concluded that pulsed electromagnetic fields might provide a mechanism to increase angiogenesis and augment healing (7). It has also been demonstrated that epidermal cells (keratocytes) and fibroblasts exposed to an electric field migrate toward the cathode (2, 5). Brown found that rabbit skin exposed to electrical stimulation demonstrated an epidermal layer that was on average twice as thick as controls (4). Additionally, it has been found that electrical stimulation increases collagen synthesis in both swine skin and human fibroblasts (3, 6). Not all VOLUME 36, NUMBER 6, 1997
457
authors, however, were successful in the duplication of these results. In an investigation using rats , Harrington et al. found that incisions treated with electrical stimulation demonstrated slower epidermal cell migration than wounds of the controls. The treatment group did however, demonstrate an increased development and organization of the dermal layer of skin with greater angiogenesis. This was attributed to the magnitude of the electric current. They felt that the higher magnitude affected cellular migration patterns rather than cellular proliferation patterns (8). These studies demonstrate that at the cellular level, the application of an electrical field can alter epithelialization, fibroblast migration, collagen synthesis, and angiogenesis; all are important components in wound healing . The antimicrobial effects of electrical stimulation have been investigated by several methods. The application of an extracellular electric field has produced a chemotactic effect on macrophages. The macrophages develop extensions of pseudopodia in the direct ion of the positive pole in much the same fashion as demonstrated by fibroblasts (9). Rowley et al. found that in vitro growth rates of Escherichiacoli and Pseudomonas aeruginosa were affected by exposure to an electric field (10). The authors noted that the application of a negative electrode to the wound site in a rabbit model served to suppress not only healing but also the infection process. In their treatment protocol, the negative electrode was kept over the wound until infection was no longer present clinically (11). Laboratory investigations of Staphylococcus aureus revealed that electrical fields can diminish growth in vitro (12). Anecdotal reports have claimed similar results in human studies (13). Wolcott et al. found a decrease in the number of pathogens cultured from 75 decubitus ulcerations treated with electrical stimulation. Unfortunately, no description of the means by which the cultures were obtained was given (14). Not all investigators have found an antimicrobial affect. Alvarez and coworkers failed to demonstrate any significant decrease in bacterial colony formation using a swine model. The investigation was limited in that the animals served as their own controls, and therefore, some residual effect of the previous treatment may have inhibited bacterial growth (3). Animal Studies
Studies using animals have demonstrated that electrical stimulation increases both perfusion and the healing rate of skin wounds (13-20) . To date, no correlation of these results to human subjects has been made (21). Unfortunately, these animal investigations demonstrate no consistency in study design and treatment methodology (3, 21-23). 458
THE JOURNAL OF FOOT & ANKLE SURGERY
Several authors speculate that changes seen with the use of electrical stimulation are attributable to an increase in tissue perfusion (16, 21, 24). Kjartansson et al., in an attempt to increase tissue perfusion, created a skin flap on the back of rats that was immediately sutured back in place. The animals then received different doses of electrical stimulation from transcutaneous electrical nerve stimulation (TENS) units. Animals treated multiple times with TENS had significantly better flap survival rates then those treated with only one stimulation. The authors theorized that electrical stimulation may improve flap survival through the release of vasodilatory neurotransmitters from small to medium sized sensory neurons, or through the activation of large diameter sensory nerves that could subsequently inhibit sympathetic vasoconstrictory neuron activity (22). Stimulation also seems to increase muscle perfusion (25-28). Myrhage and Hudlicka found increased capillary diameter and surface area in stimulated rat and rabbit musculature. They theorized this was the reason for the boost in blood flow during electrical stimulation (29). Animal models also demonstrated that cellular components of wound healing increase in the presence of an electrical field. In 1989, Cruz et al. found that electrical stimulation of bums in swine resulted in an increase in fibroblastic response, and thus faster rates of wound contracture. She also noted that at the conclusion of the 4-week investigation, 40% of the treatment group had healed wounds while none of the control animals had healed (30). Brown et al. also demonstrated an increased rate of epithelialization in 18 rabbits treated with high voltage stimulation (4). Clinical Studies
The investigations of electrical stimulation involving human subjects have primarily concentrated on wound healing, but have failed to show any consistent methodology (13-17, 24, 31, 32). Little uniformity exists in the literature with regards to duration, frequency, location of polarity, and other factors. The lack of operational definitions concerning patient selection further clouds the issue. It is interesting to note that several authors excluded patients with evidence of peripheral vascular disease, yet do not offer any description of the criteria used to define peripheral vascular disease (15, 24, 31). The lack of consistency in treatment methodology is troublesome in that it is difficult to arrive at any conclusion that is adaptable to patient use. Several authors felt that changes in polarity are important (13-15 , 17, 24, 33). Still other authors have developed specific time protocols for the application of electric stimulation [(13,16,17,24,31,33,34) Fig. 1]. A hyperemic response to electrical stimulation has been
AUTHOR _ _100 lH8 Wolcott It II
lH8
APPLICATIONTIME
DOSAGE
Not repco1ed.
SO- 100 ",", 0.2 - 0.5 v.
2 hours then 4 hours off three t:irneI 8 d a y . _ .... _ - 400-800 mIcrcMlporoo. heeling hu plot_.
NegatIve._
POLARITY
-_. -_. -_. ulcer.
Nogllllvo._ ovortho ulcer. Ctw1ge .. wound
2 hours on, 4 hours; seven days •
1878
_k.
200-1000 ,.A.
ulcer. Chongod o s _
NegatIve_ _ ovortho 2 hour atlmul8lion twice a day; 5 days COrleyend Wain_I a _ _ a 2-4 hour rocovory 300- 7OO,.A. Current rongod ""'" 30 • ulcer. Chongoos_ 1885 1101lAlan2· period. FInN"." 1888
30 _
twice dolly; 2 _
poat-
op. once a day; 5 days a
TENS: 7 pu_, 100 Hz, durotlonof 90 """,,1wtcoo_.
_,_1Not repco1ed.
PosItMt electrode • the
Kloth and FHdllr
4S _
lH8
_k.
Lundllberg lit .1
pu_, durotlon 2h.... tho __by8-10hourslater _ appIIod. Controlgroup 010.4 rna ond Irequency 0180 Hz _ on _ _ pIacabot'or 2 houn twice a -.oIty at _ _ _ whlchtlngllng ..,utionilfelt. day untlllrnprovwnent or 7 days.
Not reportad.
1 houroll8-10houn. T h e n _ StmuI8lion at 0.2 ..... ond frequencyof of . _ o s 101_ by 2 hours 90Hz.
Not reportad.
Froquencyoll05Hz, InInIpMH_of SO_ vobgaloo-175V. ~
1888
Kja .... nuon and Lu_rg 1880
....net.1 1880
FHd.,out 1881
LundaMrgatol 1882
_wave
~.
a day; no longer thon 90
hours _
_.
4- 8 MonophasIc pulaad oulTOlll_ a pulaad traalmento lor 7 days. Iroquency of 129 ppoampllluda 0135 mAo
20 minuta 1wtcoa day lor up 10 11
AIIem8tian conll8nt lquar&-WllVe pulses (pullo width 1.....) at intano~ poroothasIIa.
78 _
poIIonts_
RESULTS
WOUND
V....,._ ulconllk>n8
-
ulconllk>n8 (not
_(not _lOCI)
106 ulcera.
Report o f _ COOlI reporto oNof tho ulconl-.. repco1ed os <:OIl1lIOI01y healed in 7, 32 ond 42 days. 40% of thou_ _ complotoly.
NagatIvoat tho ulcer. Then changed as-.nd
progrouad
_in_group_ollgn_ _1n-,,_(1.5102.5_)In_1
Treatment group of 15:
I_u_ (not_,
Treatment group of 18;
Pook>p~ IU8 ond g _ 0 ' - higher Inaoue in ..... intho_group. (Symo's, BKA, 11<) _
canlroI 0133.
Treatment group 9: control group of 7.
Troatmenlgroup 0118: control group 0119.
Not repco1ed.
A. . . . hooIklg_ofU_intho_ 48 of tho _ _ complotoly_1Il oddlllonol 11 _ a ' * ' - in .... ofgrooterthlllts'll>.
canlroI 0115.
Treatment group of 12;
75Hz_Ill ImpulHwidUlof 1.3 mI.
30 mlnuta twice dally_
83 ulconl.
control group 018.
Single pullo _ourront~ a . . . . . - fIaId 0I2.8mT atolrequency of
87 poIIonts_
Treatment group of 14; canlroI group of 10.
twice a day undlllgnl of lId'lemla.
3-4 _ days.
Three cue reports .
doIInod)
NegatIve _ _ ovortho
Gault and G_na
POPULATION
ovortho
Treatment group of 28: control group of 24.
PoIor1ly changad -.. oach Treatment group of 32; control group 0132.
treatment.
-.._
Treatment group 11II_ by 7.3_, ata Stage IV decubltuo haaIIng _ 01_ per_ contnll group had ond _ in -.rid slleof29.9'll>. Pook>p
. . - in_
...-y
'ParftlX' _dopplar-.otor.
--
group had oIgn-.uy higher .. meuurod by tho
blood _ _ tho 8th _
Pook>p skin flap
Treatment group _
V....,._ u_
No IIgnIllcantdllleronce _ days.
Mull/plo(otaolo,
T_group _ a grooterd_ In"" at oach _1<1 moaouromontlor 4 weeki.
deoutlIIus,ourgIcal, traumatic)
Venousstull ulcllratlons
a slgnlllcant Incroa8e in _Immedlatoly ond at 2-8 days.
groupo ""'" 0-90
Two groupo _ _ s oIgnlllcantdllleronos In pon>entago of poIIontsheslad at 8 and 12 _1<1. IUooallgnlllcant dllloronce In docroaoo In ulcer"" _th.groupo.
Not reportad.
HIgh vobga galvanic__1atIon.
Not reportad.
ToIaIof 14 pat_ dlvldod into3_andono oontrolgroup.
Preuure 80nII 01 Graataol chango Inwound sIz..... in group naiad groal«then3_ wMh.-':ll1imulatlonoJono. durotlon
Alan at stl888
1 hour 3 days per_k.
Monophaolcpulaad HV alImulator oat at oontInuouomodo at puloo _ of 80 ppo.
PoaIlIveelectrodeover the ulcllratlon.
15 ambul8lory poIIonts;no oontn>I group.
0 _ foot
Bokor at stl997
1.5 hours dally.
Variable (asymmotrIc b1phao1c atlmul8lion). Pooltlvo_.dlslally.
Ake... and Oablalaon
1984
ulcanlllono
80 toIaI patIontoIn4 groupo: DIobatlc lag and including20 palIant oontn>I foot ulcerations group.
12 poIIonts_ In a moon period of 2.8 months. No IIgnll'lc8nt difference In the healing time or ulcer .... _ tho UOIof tho oIoc:trical alImulollon.
No oIgnlllcentdllloronce _
groupo.
FIGURE 1 A review of some of the literature using electrical stimulation as an adjunct therapy for wound healing. Little constancy is seen throughout.
suggested by several authors (35). Increased perfusion to the lower extremity by stimulation of the gastrocnemeous or spinal nerve roots have been achieved in test subjects (36, 37). Several authors reported accelerated healing of "ischemic ulcerations" with the use of electrical stimulation. These results are questionable, because the authors state that patients with peripheral vascular disease were excluded. No explanation of the criteria for exclusion or definition of ischemic ulcers was offered (15,35). Gault found that ischemic wound healing rates could be "doubled" with the use of electrical stimulation. Unfortunately, no analysis or description of wound selection was reported (33). Additionally, Baker et al., in a prospective study, found that diabetic wound healing could be accelerated with the use of electrical stimulation, but the operational definitions and methodology of this report are also suspect (35). Lundeberg et al. and Kjartansson et al. both investigated the use of external electrical stimulation as a means to combat ischemia of
skin flaps. They found a significant increase in the perfusion, as measured with a laser doppler flowmeter (18, 34). It is interesting to note that while both studies were conducted by the same authors, the method of delivering the electrical stimulation was different. Conclusion
There are a number of reports in the medical literature that suggest that the application of electrical current may enhance wound healing through proliferation and migration of both epithelial cells and connective tissue cells, which are pivotal components in the pathway of wound healing. Unfortunately, there is a lack of continuity of device and means of application, which make it difficult to apply these findings to patients. The literature is devoid of a sound investigation of electrical stimulation and its effect on the diabetic foot. Decreased local tissue perfusion and the resultant localized tissue hypoxia are contributing factors in many cases of diaVOLUME 36, NUMBER 6, 1997
459
betic neuropathic ulceration and resultant amputations (38). Once a wound has formed, there is an increased oxygen requirement to allow healing to occur (39). If the electrical stimulation device could help combat these factors, then ulcer healing times would be reduced and the risk of amputation diminished. It is clear that a well designed investigation is needed to aid in the development of criteria for treatment of all wound types. The diabetic wound, with its diverse pathological components, could benefit most from the advantages this therapy seems to offer. The potential increase in perfusion should be evaluated more thoroughly as a means of promoting soft tissue healing in high-risk diabetic patients. Carley and Wainapel point out that both the protocol and the bulky equipment need to be redesigned in an effort to allow ease of use and to increase their practical applications (13). To that end, the development of a dacron garment as described by Dimitrijevic might allow ease of application, and thus, ease of treatment (40).
21.
References
22.
1. Kanof, N. Gold leaf in treatment of cutaneous ulcers . J. Invest. Dermatology 43:441-442, 1964. 2. Cooper, M. S., Schliwa, M. El ectrical and ionic controls of tissue cell locomotion in DC electric fields. J. of Neurosci. Res . 13:223244, 1985. 3. Alvare z, O. M., Mertz, P. M., Smerbeck, R. V., Eaglstein, W. H . The healing of superficial skin wound s is stimulated by extern al electrical current. J. Invest. Dermatol. 81:144-148, 1983. 4. Brown, M., McDonnell, M. K., Menton, D. N. Polarity effects on wound healing using electric stimulation in rabbits. Arch . of Phys. Med . Rehabil. 70:624-627, 1989. 5. Erickson, C. A., Nuccitelli, R. Embryonic fibroblast motility and orientation can be influenced by physiological electric fields . J. Cell BioI. 98:296-307, 1984. 6. Bourguignon, G. J., Bourguignon , M., Bourguignon, L. Y. Effect of high voltage pulsed galvanic stimulation on human fibroblasts in cell culture-a model system of soft tissue healing. J. Am. Phys. Ther. Assoc. 1:9, 1986. 7. Arneia Yen-Patton, G. P., Patton, W. F ., Beer, D. M., Jacobson, B. S. Endothelial cell response to pulsed electromagnetic field: Stimulation of growth rate and angiogenesis in vitro. J. Cell . Physiol. 134:37-46, 1988. 8. Harrington, D . B., Meyer, R., Klein, R. M. Effects of small amounts of electric current at the cellular level. Ann. N. Y. Acad. Sci. 238:300-306, 1974. 9. Orida, N. Directional protrusive pseudopodial activity and motility in macrophages induced by extr acellular electric fields. Cell Motil . 2:243- 255, 1982. 10. Rowley, B. A. Electrical current effects on E. coli growth rates. Proc. Soc. Exp. BioI. Med . 139:929-934, 1972. 11. Rowley, B. A., McKenna, J. M., Chase, G. R. The influence of electrical current on an infecting microorganism in wounds. Ann. N. Y. Acad. Sci. 238:543-551, 1974. 12. Barranco, S. D., Spadaro, J. A., Berger, T . J., Becker, R. O.In Vitro effect of weak direct current on Staphylococcus aureus. Clin . Orthop. ReI. Res. 100:250-255, 1974. 13. Carley, P. J., Wainapal, S. F . Electrotherapy for acceleration of
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THE JOURNAL OF FOOT & ANKLE SURGERY
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35. Baker, L. L., Chambers, R., DeMuth, S. K., Villar, F. Effects of electrical stimulation on wound healing in patients with diabetic ulcers. Diabetes Care 20:405-412, 1997. 36. Currier, D. P. Electrical stimulation effect on localized blood (Abstract). Phys. Ther. 63:761, 1983. 37. Dooley, D. M., Kasprak, M. Modification of blood flow to the extremities by electrical stimulation of the nervous system. South. Med. J. 69:1309-1311, 1976.
38. Hauser, C. J., Klein, S. R., Mehringer, C., Appel, P., Shoemaker, W. C. Assessment of perfusion in the diabetic foot by regional transcutaneous oximetry. Diabetes 33:527-531, 1984. 39. La Van, F. B., Hunt, T. K. Oxygen and wound healing. Clin. Plast. Surg. 17:463-472, 1990. 40. Dimitrijevic, M. M. Mesh-Glove. A method for whole-hand electrical stimulation in upper motor neuron dysfunction. Scand. J. Rehabil. Med. 26:183-186, 1994.
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