A Review of Microvascular Measurements in Wound Healing

Abstract

The microcirculatory evaluation in patients affected by arteriopathic or venous ulcers is usually carried out using laser Doppler flowmetry, transcutaneous oxygen (transcutaneous pressure of oxygen, TcPO₂), and carbon dioxide (transcutaneous pressure of carbon dioxide, TcPCO₂) measurements and capillaroscopy. These techniques provide significant pathophysiologic and prognostic information. TcPO₂ and TcPCO₂ diagnose and classify the extent of arterial disease in the leg ulcers caused by arterial disease; the prognostic value is recognized, though doubts about its prognostic potential exist in the case of leg ulcer. Laser Doppler flowmetry is able to identify the first functional impairment in the early stages of the arterial disease and in the complicated venous insufficiency. Capillaroscopy gives us morphological and quantitative parameters of the capillary bed that is damaged in arteriopathic and venous ulcers; nevertheless, it does not provide us with definite prognostic indexes. Combining the 3 methods may contribute to yield objective measures in the clinical management of lower extremity ulcers.

Keywords

microcirculation laser Doppler flowmetry TcPO2 TcPCO2 capillaroscopy leg ulcers arterial ulcers venous ulcers

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References

Curri SB. Microvascular anatomy of the skin and its appendages . Phlebologie 1990;43(3): 407-430.

Braverman IM. The cutaneous microcirculation . J Invest Dermatol Symp Proc 2000;5(1): 3-9.

Braverman IM. The role of blood vessels and lymphatics in cutaneous inflammatory processes: an overview . Br J Dermatol 1983;109(Suppl. 25): 89-98.

Stern MD. In vivo evaluation of microcirculation by coherent light scattering . Nature 1975;254(5495): 56-58.

Nilsson GE , Tenland T , Oberg PA. Evaluation of a laser Doppler flowmeter for measurement of tissue blood flow. IEEE Trans Biomed Eng 1980;27: 597-604.

Braverman IM , Keh A , Goldminz D. Correlation of laser Doppler wave patterns with underlying microvascular anatomy. J Invest Dermatol 1990;95(3): 283-286.

Braverman IM , Schechner JS , Silvermann DG , et al. Topographic mapping of the cutaneous microcirculation using two output of laser-Doppler flowmetry: flux and the concentration of moving blood cells. Microvasc Res 1992;44(1): 33-48.

Braverman IM. The cutaneous microcirculation: ultrastructure and microanatomical organization . Microcirculation 1997;4(3): 329-340.

Colantuoni A , Bertuglia S , Intaglietta M. Microvascular vaso-motion: origin of laser Doppler flux motion. Int J Microcirc Clin Exp 1994;14(3): 151-158.

10.

Van den Brande P , Derde MP , Von Kemp K , et al. Laser-Doppler resting fluxes, flux motion frequencies and amplitudes at the skin of the dorsum of the foot in healthy young humans. Int Angiol 1993;12(1): 40-46.

11.

Zeghal K , Geslin P , Maurel A , et al. Laser-Doppler velocimetry: a new technic for evaluating of microcirculation. A reproducibility study. Press Med 1986;15(40): 1997-2000.

12.

Hassan AA , Tooke JE. Mechanism of the postural vasoconstrictor response in the human foot. Clin Sci 1988;75: 379-387.

13.

Mellander S , Oberg B , Odelram H. Vascular adjustments to increased transmural pressure in cat and man with special reference to shifts in capillary fluid transfer. Acta Physiol Scand 1964;61: 34-48.

14.

Mahy IR , Tooke JE , Shore AC. Capillary pressure during and after incremental venous pressure elevation in man. J Physiol 1995;485: 213-219.

15.

Henriksen O , Sejrsen P , Paaske WP , et al. Effect of chronic sympathetic denervation upon the transcapillary filtration rate induced by venous stasis. Acta Physiol Scand 1983;117: 171-176.

16.

Henriksen O , Nielsen SL , Paaske WP , et al. Autoregulation of blood flow in human cutaneous tissue. Acta Physiol Scand 1973; 89: 538-543.

17.

Noddeland H , Aukland K , Nicolaysen G. Plasma colloid osmotic pressure in venous blood from the human foot in orthostasis. Acta Physiol Scand 1981;113: 447-454.

18.

Iabichella ML , Dell’Omo G , Melillo E , et al. Calcium channel blockers blunt postural cutaneous vasoconstriction in hypertensive patients. Hypertension 1997;29(3): 751-756.

19.

Williams SA , Rayman G , Tooke JE. Dependent oedema and attenuation of postural vasoconstriction associated with nifedipine therapy for hypertension in diabetic patients. Eur J Clin Pharmacol 1989;37: 333-335.

20.

Henriksen O. Local sympathetic reflex mechanism in regulation of blood flow in human subcutaneous adipose tissue . Acta Physiol Scand 1977;(Suppl. 450): 1-48.

21.

Gustafsson D , Grande PO , Borgstrom P , et al. Effects of calcium antagonists on myogenic and neurogenic control of resistance and capacitance vessels in cat skeletal muscle. J Cardiovasc Pharmacol 1988;12: 413-422.

22.

Tooke JE , Ostergren J , Fagrell B. Synchronous assessment of human skin microcirculation by laser Doppler flowmetry and dynamic capillaroscopy. Int J Microcirc Clin Exp 1983;2: 277-284.

23.

Grant RT , Bland EF. Observations on arteriovenous anastomoses in human skin and the bird’s foot with special reference to the reaction to cold. Heart 1931;15: 385-407.

24.

Hassan AAK , Rayman G , Tooke JE. Effect of indirect heating on the postural control of skin blood flow in the human foot. Clin Sci 1986;70: 577-582.

25.

Charkoudian N , Eisenach JH , Atkinson JL , et al. Effects of chronic sympathectomy on locally mediated cutaneous vasodilation in humans. J Appl Physiol 2002;92(2): 685-690.

26.

Golay S , Haeberli C , Delachaux A , et al. Local heating of human skin causes hyperemia without mediation by muscarinic cholinergic receptors or prostanoids. J Appl Physiol 2004;97(5): 1781-1786. Epub 2004 Jul 9.

27.

Wilson TE , Cui J , Crandall CG. Mean body temperature does not modulate eccrine sweat rate during upright tilt. J Appl Physiol 2005;98(4): 1207-1212. Epub 2004 Dec 3.

28.

Arora S , Smakowski P , Frykberg RG , et al. Difference in foot and forearm skin microcirculation in diabetic patients with and without neuropathy. Diabetes Care 1998;21(8): 1339-1344.

29.

Minson CT , Holowatz LA , Wong BJ , et al. Decreased nitric oxide- and axon reflex-mediated cutaneous vasodilation with age during local heating. J Appl Physiol 2002;93(5): 1644-1649.

30.

Savage MV , Brengelmann GL. Reproducibility of the vascular response to heating in human skin. J Appl Physiol 1994;76(4): 1759-1763.

31.

Iabichella ML , Mariotti R , Giannini D , et al. Dermal microcirculatory response to various stimulation tests assessed with Doppler laser. Minerva Cardioangiol 1999;47(12): 613-614.

32.

Bollinger A , Hoffmann U , Franzeck UK. Evaluation flux motion in man by the laser-Doppler technique. Blood Vessels 1991;28(Suppl. 1): 21-26.

33.

Hoffmann U , Franzeck UK , Geiger M , et al. Variability of different patterns of skin oscillatory flux in healthy controls and patients with peripheral arterial occlusive disease. Int J Microvasc Clin Exp 1993;12(3): 255-273.

34.

Hoffmann U , Franzeck UK , Bollinger A. Low frequency oscillations of skin blood flux in peripheral arterial occlusive disease. Vasa 1994;23(2): 120-124.

35.

Vracko R. Skeletal muscle capillaries in diabetics. A quantitative analysis . Circulation 1970;41: 271-283.

36.

Jeffrey S , Schechner JS , Braverman IM. Syncronous vasomotion in the human cutaneous microvasculature provides evidence for central modulation. Microvasc Res 1992;44: 27-32.

37.

Chittenden SJ , Shami SK , Cheatle T , et al. Vasomotion in the leg skin of patients with chronic venous insufficiency. Vasa 1992;21(2): 138-142.

38.

Cheatle TR , Shami SK , Stibe E , et al. Vasomotion in venous disease. J R Soc Med 1991;84(5): 261-263.

39.

Shami SK , Cheatle TR , Chittenden SJ , et al. Hyperemic response in the skin microcirculation of patients with chronic venous insufficiency. Br J Surg 1993;80(4): 433-435.

40.

Myers RR , Murakami H , Powell HC. Reduced nerve blood flow in edematous neuropathies: a biomechanical mechanism. Microvasc Res 1986;32: 145-151.

41.

Christensen NJ. Spontaneous variations in resting blood flow, postischaemic peak flow and vibratory perception in the feet of diabetics . Diabetologia 1969;5: 171-178.

42.

Abu-Own A , Scurr JH , Coleridge Smith PD. Effect of leg elevation on the skin microcirculation in chronic venous insufficiency. J Vasc Surg 1994;20(5): 705-710.

43.

Melillo E , Catapano G , Ferrari M , et al. Transcutaneous oxygen tension measurement in patients with chronic arterial obstructive disease: reliability and long term variability of the method. Angiology 1994;45(6): 469-475.

44.

Rooke TW , Osmundson PJ. Variabilità and reproducibility of transcutaneous oxygen tension measurements in the assessment of peripheral vascular disease. Angiology 1989;40(8): 695-700.

45.

Mani R. Transcutaneous measurements of oxygen tension in venous ulcer disease . Vasc Med Rev 1995;6: 121-131.

46.

Gaylarde PM , Fonseca VA , Llewellyn G , et al. Transcutaneous oxygen tension in legs and feet of diabetic patients. Diabetes 1988;37(6): 714-716.

47.

Creutzig A , Dau D , Caspary L , et al. Transcutaneous oxygen pressure measured at two different electrode core temperatures in healthy volunteers and patients with arterial occlusive disease. Int J Microcirc Clin Exp 1987;5(4): 373-380.

48.

Hauser CJ , Appel P , Shoemaker WC. Pathophysiologic classification of peripheral vascular disease by positional changes in regional transcutaneous oxygen tension. Surgery 1984;95(6): 689-693.

49.

Scheffler A , Rieger H. Clinical information content of transcutaneous oxymetry (tcpO2) in peripheral arterial occlusive disease (a review of the methodological and clinical literature with a special reference to clinical limb ischemia). Vasa 1992;21: 111-126.

50.

Fife CE , Buyukcakir C , Otto GH , et al. The predictive value of transcutaneous oxygen tension measurement in diabetic lower extremity ulcers treated with hyperbaric oxygen therapy: a retrospective analysis of 1,144 patients. Wound Repair Regen 2002;10(4): 198-207.

51.

Cheatle TR , Stibe EC , Shami SK , et al. Vasodilatory capacity of the skin in venous disease and its relationship to transcutaneous oxygen tension. Br J Surg 1991;78(5): 607-610.

52.

Malanin K , Havu VK , Kolari PJ. Dynamics of cutaneous laser Doppler flux with concentration of moving blood cells and blood cell velocity in legs with venous ulcers and in healthy legs. Angiology 2004;55(1): 37-42.

53.

Junger M , Hahn U , Bort S , et al. Significance of cutaneous microangiopathy for the pathogenesis of dermatitis in venous congestion due to chronic venous insufficiency. Wien Med Wochenschr 1994;144(10-11): 206-210.

54.

Mani R , White JE , Barrett DF , et al. Tissue oxygenation, venous ulcers and fibrin cuffs. J R Soc Med 1989;82(6): 345-346.

55.

Fagrell B.

Microcirculatory disturbances-the final cause of leg ulcers?

Vasa 1982;11: 101-103.

56.

Bollinger A , Junger M , Martz MN. Fluorescence video microscopy techniques for the evaluation of human skin micro-circulation. Prog Appl Microcirc 1986;11: 767-797.

57.

Falanga V , Moosa HH , Nameth AF , Alstadt SP , Eaglestein WH. Dermal pericapillary fibrin in venous disease and venous ulceration. Arch Dermatol 1987;123: 620-624.

58.

Browse NL , Burnand KG. The cause of venous ulceration. Lancet 1982;2(8292): 243-245.

59.

Vanscheidt W , Stengele K , Wokalek H , et al.

Peri-capillary fibrin cuffs-an O2 diffusion block?

Vasa 1991;20(2): 142-146.

60.

Nemeth AJ , Eaglstein WH , Falanga V. Clinical parameters and transcutaneous oxygen measurements for the prognosis of venous ulcers. 1989;20(2 Pt 1): 186-190.

61.

Roszinski S , Schmeller W. Differences between intracutaneous and transcutaneous skin oxygen tension in chronic venous insufficiency. J Cardiovasc Surg (Torino) 1995;36: 407-413.

62.

Michel CC. Oxygen diffusion in oedematous tissue and through pericapillary cuffs . Phlebology 1990;5: 223-230.

63.

Kolari PJ , Pekenmaki K , Pokiola RT. Transcutaneous oxygen tension in patients with post thrombotic leg ulcers: treatment with pneumatic compression. Cardiovasc Res 1988;22: 138-141.

64.

Abu-Own A , Cheatle T , Scurr JH , Coleridge Smith PJ. Effects of intermittent pneumatic compression of the foot on the micro-circulatory function in arterial disease. Eur J Vasc Surg 1993;7: 488-492.

65.

Prasad A , Ali Khan AA , Mortimer PS. Leg ulcers and oedema: a study exploring the prevalence, aetiology and possible significance of oedema in venous ulcers. Phlebology 1990;5: 181-187.

66.

Teins A , Hahn M , Junger M. Venous leg ulcers and microcirculation. Clin Hemorheol Microcirc 2001;24(3): 147-153.

67.

Junger M , Steins A , Hahn M , Hafner HM. microcirculatory dis-function in chronic venous insufficiency (CVI). Microcirculation 2000;7: S3-S12.

68.

Nicolaides AN. Chronic venous disease and the leukocyteendothelium interaction: from symptoms to ulceration . Angiology 2005;56(Suppl. 1): S11-S19.

69.

Melillo E , Iabichella L , Berchiolli R , et al. Transcutaneous oxygen and carbon dioxide during treatment of critical limb ischemia with iloprost, a prostacyclin derivative. Int J Microcirc Clin Exp 1995;15(2): 60-64.

70.

Belcaro G , Christopoulos A , Nicolaides AN. Diabetic microangiopathy treated with elastic compression—a microcirculatory evaluation using laser Doppler flowmetry, transcutaneous pO2/pCO2 and capillary permeability measurements. Vasa 1990;19(3): 247-251.

71.

Melillo E , Catapano G , Iabichella ML , et al. Transcutaneous oxygen and carbon dioxide measurement in peripheral vascular disease. Vasc Surg 1995;29(4): 273-273.

72.

Andreozzi GM. Dynamic measurement and functional assessment of tcpO2 and tcpCO2 in peripheral arterial disease . J Cardiovasc Diagnos Proc 1996;13(2): 155-155.

73.

Lalka SG , Malone JM , Anderson GG , et al. Transcutaneous oxygen and carbon dioxide pressure monitoring to determine severity of limb ischemia and to predict surgical outcome. J Vasc Surg 1988;7(4): 507-514.

74.

Sandeman DD , Shore AC , Tooke JE. Relation of skin capillary pressure in patients with insulin-dependent diabetes mellitus to complications and metabolic control. N Engl J Med 1992;327(11): 760-764.

75.

Thulesius O. Capillaroscopy with fibreoptic video microscope . Vasa 1992;21: 87-88.

76.

Curri SB. Una nuova tecnica capillaroscopica per lo studio della microcircolazione cutanea in sedi corporee di interesse dermocosmetologico: la video-capillaroscopia a sonda ottica [A new capillaroscpic technique for studying skin microcirculation in specific body areas: optic probe videocapillaroscopy] . Proceedings of XIV National Meeting of Cosmetic Medicine, Rome, April 10-12, 1992.

77.

Iabichella ML , Buti G , Manusia F , et al. Un nuovo metodo di indagine nella Malattia di Kawasaki: la biomicroscopia a sonda ottica computerizzata [A new method for studying Kawasaki Disease: optic probe computerized biomicroscopy]. Ital Heart J 2002;3(Suppl. 7): 155S-155S.

78.

Iabichella ML , Mariotti R , Buttitta F , et al. Quantitative assessment of irrigation dermal microcirculation with computerized biomicroscopy. Minerva Cardioangiol 1999;47(12): 615-616.

79.

Chazan BI , Balodimos MC , Lavine RL , et al. Capillaries of the nailfold of the toe in diabetes mellitus. Macrovasc Res 1970;2: 504-507.

80.

Iabichella ML , Mariotti R , Nuti M , et al. Site specificity of bio-microscopic pattern in diabetic patients. Minerva Cardioangiol 1999;47(12): 619-621.

81.

Fagrell B. Vital capillary microscopy. A clinical method for studying changes of the nutritional skin capillaries in legs with arteriosclerosis obliterans . Scand J Clin Lab Invest 1973;(Suppl 133): 2-50.

82.

Vayssairat M , Le Devehat C. Critical analysis of vascular exploration in diabetic complications. J Mal Vasc 2001;26(2): 122-125.

83.

Melillo E , Piaggesi A , Menegato A , et al. La microangiopatia diabetica nella eziopatogenesi del piede diabetico [Diabetic microangiopathy in the pathophysiology of diabetic foot]. Min Cardiangiol 2001;49(6 Suppl. 1): 291-292.

84.

Melillo E , Ferrari M , Balbarini A , et al. Transcutaneous gases determination in diabetic critical limb ischemia. Diabetes Care 2005;28: 2081-2082.

85.

Gschwandtner ME , Koppensteiner R , Maca T , et al. Spontaneous laser Doppler flux distribution in ischemic ulcers and the effect of prostanoids: a crossover study comparing the acute action of prostaglandin E1 and iloprost vs saline. Microvasc Res 1996;51(1): 29-38.

86.

Buttitta F , Iabichella ML , Limbruno U , et al. Changes in iliac and femoral artery following percutaneous interventional procedures: preliminary report. Heart Int 2005;1(4 no 1): 73-78.

87.

Delis KT , Lennox AF , Nicolaides AN , et al. Sympathetic autoregulation in peripheral vascular disease. Br J Surg 2001;88(4): 523-528.

88.

Melillo E , Nuti M , Pedrinelli R , et al. Prognostic values of transcutaneous oxygen and carbon dioxide measurements in patients with lower limb critical ischemia. Abstr Eur Heart J 2005;26: 701-701.

89.

Samson RH , Gupta SK , Goldstein R , et al. Evaluation of peripheral arterial disease using a transcutaneous oxygen tension sersor. In: Huch R , Huch A , editors. Continuous transcutaneous blood gas monitoring. New York: Marcel Dekker; 1983. p. 698-695.

90.

Wyss CR , Matsen FA 3rd , Simmons CW , et al. Transcutaneous oxygen tension measurements on limbs of diabetic and nondiabetic patients with peripheral vascular disease. Surgery 1984;95(3): 339-346.

91.

Bongard O , Krahenbuhl B. Pedal blood flow and transcutaneous PO2 in normal subjects and in patients suffering from severe arterial occlusive disease. Clin Physiol 1984;4(5): 393-401.

92.

Becker F , Gabrielle F , Raoux MH , et al. Value of measuring transcutaneous oxygen pressure in arterial disease of the legs. Ann Cardiol Angeiol (Paris) 1989;38(8): 465-472.

93.

Ubbink DT , Spincemaille GH , Reneman RS , et al. Prediction of imminent amputation in patients with non-reconstructible leg ischemia by means of microcirculatory investigations. J Vasc Surg 1999;30(1): 114-121.

94.

Melillo E , Pedrinelli R , Nuti M , et al.

Can limb loss in patients with lower limb critical ischemia (CLI) be predicted by transcutaneous oxygen and carbon dioxide measurements?

Int Angiol 2004;23(1): 197-197.

95.

Melillo E , Ferrari M , Balbarini A , et al. Transcutaneous oxygen and carbon dioxide levers with Iloprost administration in diabetic limb ischemia. Vasc Endovasc Surg. Forthcoming.

96.

Mayrovitz HN , Larsen PB. Periwound skin microcirculation of venous leg ulcers. Microvasc Res 1994;48(1): 114-123.

97.

Coleridge Smith PD , Thomas P , Scurr JH , et al. Causes of venous ulceration: a new hypothesis. Br Med J 1988;296(6638): 1726-1727.

98.

Mlacak B , Blinc A , Gale N , Ivka B. Microcirculation disturbances in patients with venous ulcer before and after healing as assessed by laser Dopler flux-metry. Arch Med Res 2005;36(5): 480-484.

99.

Ardron ME , Helme RD , McKernan S. Microvascular skin responses in elderly people with varicose leg ulcers. Age Ageing 1991;20(2): 124-128.

100.

Reinhardt F , Wetzel T , Vetten S , et al. Peripheral neuropathy in chronic venous insufficiency. Muscle Nerve 2000;23(6): 883-887.

101.

Pryce DW , Friedmann PS. Hemodynamics of leg ulceration assessed by laser Doppler flowmetry. J Am Acad Dermatol 1993;29(5 Pt 1): 708-714.

102.

Luetolf O , Bull RH , Bates DO , et al.

Capillary underperfusion in chronic venous insufficiency: a cause for leg ulceration?

Br J Dermatol 1993;128(3): 249-254.

103.

Junger M , Hahn M , Klyscz T , et al. Influence of healing on the disturbed blood flow regulation in venous ulcers. Vasa 1996; 25(4): 341-348.

104.

Malanin K , Kolari PJ , Havu VK. The role of low resistance blood flow pathways in the pathogenesis and healing of venous leg ulcers. Acta Dermatol Venereol 1999;79(2): 156-160.

105.

Secomb TW , Fleishman GJ , Papenfuss HD , et al. Effect of reduced perfusion and hematocrit on flow distribution in capillary networks. Prog Appl Microcirc 1987;12: 205-211.

106.

Bollinger A , Leu AJ , Hoffmann U , et al. Microvascular changes in venous disease: an update. Angiology 1997;48(1): 27-32.

107.

Thum J , Caspary L , Creutzig A , et al. A new method for the assessment of tissue hemoglobin oxygenation in patients with chronic venous insufficiency. Microvasc Res 1996;51(3): 317-326.

108.

Shami SK , Cheatle TR , Chittenden SJ , et al. Hyperaemic response in the skin microcirculation of patients with chronic venous insufficiency. Br J Surg 1993;80(4): 433-435.

109.

Netten PM , Wollersheim H , Thien T , et al. Skin microcirculation of the foot in diabetic neuropathy. Clin Sci (Lond) 1996; 91(5): 559-565.

110.

Petrofsky J , Schwab E , Lo T , et al. Effects of electrical stimulation on skin blood flow in controls and in and around stage III and IV wounds in hairy and non hairy skin. Med Sci Monit 2005;11(7): CR309-CR316. Epub 2005 Jun 29.

111.

Rendell MS , Milliken BK , Finnegan MF , et al. The microvascular composition of the healing wound compared at skin sites with nutritive versus arteriovenous perfusion. J Surg Res 1998;80(2): 373-379.

112.

Rendell Ms , Milliken BK , Finnegan MF , et al. The skin blood flow response in wound healing. Microvasc Res 1997;53(3): 222-234.

113.

Falanga V , McKenzie A , Eaglstein WH. Heterogeneity in oxygen diffusion around venous ulcers. J Dermatol Surg Oncol 1991; 17(4): 336-339.

114.

Sheffield PJ. Measuring tissue oxygen tension: a review . Undersea Hyperb Med 1998;25(3): 179-188.

115.

Melillo E , Iabichella ML , Berchiolli R , et al. Transcutaneous oxygen and carbon dioxide measurements and laser-Doppler flowmetry in the assessment of periulcerous leg skin microcirculation. Phlebology ’95. Negus D, Jantet G, Coleridge Smith PD, editors. London: Springer Verlag; 1995 2(Suppl. 1): 826-828.

116.

Gschwandtner ME , Ambrozy E , Fasching S , et al. Microcirculation in venous ulcers and the surrounding skin: findings with capillary microscopy and a laser Doppler imager. Eur J Clin Invest 1999;29(8): 708-716.

117.

Gschwandtner ME , Ambrozy E , Maric S , et al. Microcirculation is similar in ischemic and venous ulcers. Microvasc Res 2001; 62(3): 226-235.

118.

Mani R , Vowden K , Nelson EA. Intermittent pneumatic compression for treating venous leg ulcers. Cochrane Database Syst Rev 2001;(4): CD001899.

119.

Roberts G , Hammad L , Collins C , et al. Some effects of sustained compression on ulcerated tissues. Angiology 2002;53(4); 451-456.

120.

Partsch H , Horakova MA. Compression stokings in treatment of lower leg venous ulcer. Wien Med Wochenschr 1994;144 (10-11): 242-249.

121.

Jorneskog G , Brismar K , Fagrell B. Low molecular weight heparin seems to improve local capillary circulation and healing of chronic foot ulcers in diabetic patients. Vasa 1993; 22(2): 137-142.

122.

Omar AA , Mavor AI , Jones AM , et al. Treatment of venous leg ulcers with Dermagraft. Eur J Vasc Endovasc Surg 2004;27(6): 666-672.

123.

Reutter H , Bort S , Jung MF , et al. Questionable effectiveness of autologous platelet growth factors (PDWHF) in treatment of venous ulcers of the leg. Hautarzt 1999;50(12): 859-865.