Evidence is reviewed (8 studies involving 215 clinical patients with ischemic skin ulcers and 7 animal tissue or tissue culture studies) that electrical stimulation of fibroblast cells accelerates the intracellular biosynthesis necessary to form new granulation tissue in a healing wound, and that both a direct local tissue effect and a circulatory improvement occur.
A model is presented in which transmembrane currents open voltage-controlled calcium channels in fibroblast cells, causing ATP resynthesis, activation of protein kinase mechanisms to synthesize new cellular protein, and the DNA replication necessary for mitotic cell division. Stimulation efficacy appears to be determined by a number of basic electrical parameters, and judicious waveform control is desirable.
AkermanKEONichollsDG: Physiological and bioenergetic aspects of mitochondrial calcium transport. Rev Physiol Biochem Pharmacol95:149-201,1983
2.
AlonGAzariaMSteinH: Diabetic ulcer healing using high voltage TENS. Phys Ther66,775. 1986
3.
AlvarezOMMertzPMSmerbeckRVEaglsteinWH, The healing of superficial skin wounds is stimulated by external electrical current. J Invest Dermatol81(2); 144-148. 1983
4.
AssimacopoulosD: Low intensity negative electric current in the treatment of ulcers of the leg due to chronic venous insufficiency. A report of three cases. Am J Surg115:683-687, 1968.
5.
AugustinssonLECarlssonCAHolmJJivegardL: Epidural electrical stimulation in severe limb ischemia. Pain relief, increased blood flow, and a possible limb saving effect. An Surg202(1 ) : 104-110, 1985
6.
BarkerATJaffeLFVanableJWJr: The glabrous epidermis of cavies contains a powerful battery. Am J Physiol242 :R358-R366, 1982.
7.
BarronJJJacobsonWETiddG: Treatment of decubitus ulcers. A new approach. Minn Med68(2): 103-106, 1985
8.
BourguignonGJBourguignonLYW: Electric stimulation of protein and DNA synthesis in human fibroblasts. FASEB J. 1(5):398-402. 1987
9.
BourguignonLYWWenoheJMajercikMHBourguignonGJ: Lymphocyte activation and capping of hormone receptors. J Cell Biochem37:131-150,1988
10.
BourguignonLYW, J. Cell. Physiol, (in press)
11.
CampbellAK: Intracellular Calcium. John Wiley and Sons, New York, 1983
12.
CarleyPJWainapelSF: Electrotherapy for acceleration of wound healing: low intensity direct current. Arch Phys Med Rehabil66(7):443-446, 1985
13.
ChenCHessP: Calcium Channels in mouse 3T3 and human fibroblasts. Biophys J. 51 :226a, 1987
14.
ChengNVan HoffHBockxEHoogmartensMJMulierJCDedijckerFJSansenWMDeLoeckerW: The effects of electric currents on ATP generation, protein synthesis and membrane transport in rat skin. Clin Orthopaedics and Rei Res171:264-272,1982
15.
CookAWOygarABaggenstosPPachecoSKlerigaE: Vascular disease of extremities. Electric stimulation of spinal cord and posterior roots. NY State J Med76:366-368,1976
16.
CookAWTahmouresieA, et al, Epidural electrical stimulation of spinal cord for intractable pain and other abnormal conditions. Acupuncture & Electro-Ther Res, Int J,2:259-270, 1977.
17.
DentonRMMcCormackJG: On the role of the calcium transport cycle in heart and other mammalian mitochondria. FEBS Letters119:1-8,1980
18.
DouvasASHarringtonCABonnerJ: Major nonhistone proteins of rat liver chromatin: Preliminary identification of myosin, actin, tubulin, and tropomyosin. Proc Natl Acad Sei USA72:3902-3906,1975
19.
Dubois-ReymondE: Untersuchungen ueber tierische elektrizitaet, Vol II, Reimer, Berlin, 1860
20.
Fitton-JacksonSFBassetCAL: in Tissue Culture in Medical Research (II), RichardsRJRajanKT, eds, pp 21-28, Pergamon Press, Oxford, 1980
21.
GaultWGatensP: Use of low intensity dipept current in management of ischemic skin ulcers. Physical Therapy56(3):-265-269. 1976
22.
GrinvaldAFarberIC: Optical recording of calcium action potentials from growth cones of cultured neurons with a laser microbeam. Science212:1164-1167. 1981
23.
JohanssonB: Circulatory responses to stimulation of somatic afferents. Acta Physiol Scand57 (Supp 198), 1-85, 1962
24.
HarringtonDB, Becker RU: Electrical stimulation of RNA and protein synthesis in the frog erythrocyte. Exp Cel Res76:95-98. 1973
25.
KaadaB: Promoted healing of chronic ulceration by transcutaneous nerve stimulation TNS. VASA Band12, 262-269, 1983
26.
KleyN: Multiple regulation of proenkephalin gene expression by protein kinase C, J Biol Chern263(4):2003-2008. 1988
27.
KorensteinRSomjenDFischlerHBindermanI: Capacitive pulsed electric stimulation of bone cells: induction of cyclic-AMP changes and DNA synthesis. Biochim et Biophys Acta803:302-307. 1984
28.
KlothLCFeedarJA: Acceleration of wound healing with high voltage, monophasic, pulsed current. Phys Ther68(4):503-508. 1988
29.
LaneJF, Electrical impedances of superficial limb tissues: epidermis, dermis and muscle sheath, Ann NY Acad Sci170:812-825. 1970.
30.
LiboffARWilliamsTJrStrongDMWistarRJr: Time-varying magnetic fields: effect on DNA synthesis. Science223:818-820. 1984
31.
LokhaMJMasuiY: Effects of Ca2+ ions on the formation of metaphase chromosomes and sperm pronuclei in cell-free preparations from unactivated Rana pipiens eggs. Dev Biol103:434-442. 1984
32.
MarcumJMDedmanJRBrinkleyBRMeansAR: Control of microtubule assembly-disassembly by calcium-dependent regulation protein. Proc Natl Acad Sci, USA75:3771-3775, 1978
33.
McCormackJG: Characterization of the effects of Ca2+ on the intramitochondrial Ca2+-sensitive enzymes from rat liver and within intact rat liver mitochondria. Biochem J231:581-595. 1985
34.
OmuraY: The relationship between the transmembrane action potential and the voltage-time-dependent, negative resistance characteristics of the voltagecurrent curves of excitable pacemaker’and nonpacemaker cell membranes. Transactions of the New York Academy of Sciences. Series II 33 No. 5:467-518,1971
35.
OmuraYLeeKJeronimoM: Stimulation of excitable cell membranes by capacitive current and rapidly changing electro-magnetic field without direct contact between electrodes and the cells. Fed Proc, 31 : presented at the annual scientific meeting of the FASEB, Atlantic City, April14, 1972
36.
OmuraYLeeK: The effects of acupuncture (AC) on cardiovascular and nervous systems, p 48, Abstracts 2:48 of the 19th Ann Scientific Meeting of the Am Soc for Artificial Internal Organs, Boston, Mass, April7-9, 1973
37.
OmuraY: Pathophysiology of acupuncture treatment: effects of acupuncture on cardiovascular and nervous systems. Acupuncture & Electro-Therapeutics Research, Int J1:51-141,1975
38.
OmuraY: Electro-acupuncture: its electro-physiological basis and criteria for effectiveness and safety—Part 1. Acupuncture & Electro-Ther Res, Int J1:157-181,1975
39.
OmuraY: Editorial: Simple custom-made disposable surface electrode system for non-invasive “electroacupuncture” or TNS and its clinical applications including treatment of cephalic hypertension and hypotension syndromes as well as temporo-mandlbular joint problems, tinnitus, shoulder and lower back pain, etc. Acupuncture & Electro-Ther Res, Int J6:109-134, 1981.
40.
OmuraY, Editorial: Non-invasive circulatory evaluation and electro-acupuncture & TES treatment of diseases difficult to treat in Western medicine: 1) abnormal brain circulation and blood pressure: cephalic hypertension or cephalic hypotension syndromes and their related conditions—headache, insomnia, blindness due to macular degeneration & retinitis pigmentosa, and some psychiatric problems; 2) severe lower extremity circulatory disturbances with intractable pain, intermittent claudication, ulceration and/or severe diabetic neuropathy. Acupuncture & Electro-Ther Res, Int J8:177-255,1983
41.
OmuraY: Electrical parameters for safe and effective electro-acupuncture and transcutaneous electrical stimulation: threshold potentials for tingling, muscle contraction and pain; and how to prevent adverse effects of electro-therapy—Part 1. Acupuncture & Electro-Ther Res, Int J10:335-337,1985
42.
OmuraY: Electrical parameters for safe and effective electro-acupuncture and transcutaneous electrical stimulation, Acupuncture and Electro-ther Res, Int J, 10:335-337, 1985
43.
OmuraY: Basic electrical parameters for safe and effective electro-therapeutics. Acupuncture & Electrother Res, Int J12:201-225, 1987
44.
PfennlngerKH: Of nerve growth cones, leukocytes and memory: second messenger systems and growth-regulated proteins. Trends Neurosci9:562-565,1986
45.
PoonCSChoyTTC: Transient response studies of biological cell impedance. Med Biol Eng & Comp16, 633-640, 1978
46.
ReillyJPFreemanVTLarkinWD: Sensory effects of transient electrical stimulation-evaluation with a neuroelectric model. IEEE Trans Blomed Engr BME-32, 1001-1011, 1985
47.
RosendalT: Studies on the conducting properties of human skin to direct current Acta Physiol Scand. 5:130-151, 1943
48.
SeppaHGrotendorstGSeppaSSchiffmannEMartinGR: Platelet-derived growth factor is chemotactic for fibroblasts. J Cell Biol92:584-588. 1982
49.
ShepherdGM: Neurobiology, 2nd Ed, Oxford University Press, New York, 1988
50.
SikorskaMWhitfieldJFWalkerPR: The regulatory and catalytic subunits of cAMP-dependent protein kinases are associated with transcriptionally active chromatin during changes in gene expression. J Biol Chern263(6):3005-3011. 1988
51.
ShteyerANortonLA, Rodan GA: Electromagnetically induced DNA synthesis in calveria cells. J Dent Res59:362 (Abstr) 1980
52.
TsukamotoYHelselWEWahlSM: Macrophage production of fibronectin, a chemoattractant for fibroblasts. J Immunol127:673-678,1981
53.
WolcottLEWheelerPCHardwickeHMRowleyBA: Accelerated healing of skin ulcers by electrotherapy: preliminary clinical results. Southern Med J62:795-801, 1979
54.
YamamotoY: Electrical properties of the epidermal stratum corneum. Med Biol Eng14:151-158,1976
55.
YoungHG: Electric impulse therapy aids wound healing. Mod Vet Pract47:60-62,1966
