Models to Study Ischemia in Chronic Wounds

Abstract

Wound healing is a complex immune response designed to achieve tissue repair following injury. Imbalance of stimulating and inhibiting factors cause failure of healing. Ischemia is a major cause of wound repair dysregulation and may be limb and life threatening. Investigating ischemic wound healing using animal models minimizes the complex accompanying factors that are usually present in humans, such as age or diabetes. This paper presents a limited review on normal physiological healing and on models that are used to study compromised healing under ischemic conditions.

Keywords

wound healing ischemia animal model

Get full access to this article

View all access options for this article.

References

Schäffer M , Barbul A. Lymphocyte function in wound healing and following injury. Br J Surg 1998;85:444.

Downey GP. Mechanisms of leukocyte motility and chemotaxis . Curr Opin Immunol 1994;6:113.

Schäffer M , Becker HD. Immunregulation der Wundheilung. Chirurg 1999;70:897-908.

Leibovich SJ , Ross R. The role of the macrophage in wound repair. Am J Pathol 1975;78:71.

Subramaniam M , Saffaripou S , Van de Water L , Frenette PS. Role of endothelial selectins in wound repair. Am J Pathol 1997;150:1701.

Fishel RS , Barbul A , Beschorner WE , et al. Lymphocyte participation in wound healing. Ann Surg 1987;206:25-29.

Ross R , Beneditt EP. Wound healing and collagen formation. Fine structure in experimental surgery. J Cell Biol 1969;40:366-381.

Efron JE , Frankel HL , Lazarou SA , et al. Wound healing and T-lymphocytes. J Surg Res 1990;48:460-463.

Barbul A , Breslin RJ , Woodyard JP , et al. The effect of in vivo T helper and T suppressor lymphocyte depletion on wound healing. Ann Surg 1989;209:479-483.

10.

Davis PA , Corless DJ , Aspinall R , et al. Effect of CD4 and CD8 depletion on wound healing. Br J Surg 2001;88:298-304.

11.

Barbul A , Shaw T , Rotter SM , et al. Wound healing in nude mice: a study on the regulatory role of lymphocytes in fibroplasia. Surgery 1989;105:764-769.

12.

Schäffer M , Efron PA , Thornton FJ , et al. Nitric oxide, an autokrine regulator of wound fibroblast synthetic function. J Immunol 1997;158:2375-2381.

13.

Nwomeh BC , Liang HX , Diegelmann RF , et al. Dynamics of the matric metalloproteinases MMP-1 and MMP-8 in acute open human dermal wounds. Wound Repair Regen 1998;6:127.

14.

DiPietro LA , Nissen NN , Gamelli RL , et al. Thrombospondin 1 synthesis and function in wound repair. Am J Pathol 1996;148:1851.

15.

Gottrup F , Agren MS , Karlsmark T. Models for use in wound healing research: a survey focusing on in vitro and in vivo adult soft tissue. Wound Repair Regen 2000;8:83-96.

16.

Davidson JM. Animal models for wound repair . Arch Dermatol Res 1998;290(Suppl):S1-S11.

17.

McFarlane RM , DeYound G , Henry RA. The design of a pedicle flap in the rat to study necrosis and its prevention. Plast Reconstr Surg 1965;35:177.

18.

Dunn RM , Mancoll J. Flap models in the rat: a review and reappraisal. Plast Reconstr Surg 1992;90:319-328.

19.

Sullivan TP , Eaglstein WH , Davis SC , et al. The pig as a model for human wound healing. Wound Repair Regen 2001;9:66-76.

20.

Hahn EW , Peschke P , Mason RP , et al. Isolated tumor growth in a surgically formed skin pedicle in the rat: a new tumor model for NMR studies. Magn Reson Imaging 1993;11:1007-1017.

21.

Quirinia A , Jensen FT , Viidik A. Ischemia in wound healing. I: Design of a flap model—changes in blood flow. Scand J Plast Reconstr Surg Hand Surg 1992;26:21-28.

22.

Quirinia A , Viidik A. Ischemia in wound healing. II: Design of a flap model—biomechanical properties. Scand J Plast Reconstr Surg Hand Surg 1992;26:133-139.

23.

Schwarz DA , Lindblad WJ , Rees RS. Altered collagen metabolism and delayed healing in a novel model of ischemic wounds. Wound Repair Regen 1995;3:204-212.

24.

Martson M , Viljanto J , Laippala P , Saukko P. Cranio-caudal differences in granulation tissue formation: an experimental study in the rat. Wound Repair Regen 1999;7:119-126.

25.

Rochester JR , Brown NJ , Reed MW. Characterisation of an experimental model of chronic lower limb ischaemia in the anaesthetised rat. Int J Microcirc Clin Exp 1994;14:27-33.

26.

Goldstein B , Sanders J. Skin response to repetitive mechanical stress: a new experimental model in pig. Arch Phys Med Rehabil 1998;79:265-272.

27.

Salcido R , Fisher SB , Donofrio JC , et al. An animal model and computer-controlled surface pressure delivery system for the production of pressure ulcers. J Rehabil Res Dev 1995;32:149-161.

28.

Swaim SF , Bradley DM , Vaughn DM , et al. The greyhound dog as a model for studying pressure ulcers. Decubitus 1993;6:32-40.

29.

Peirce SM , Skalak TC , Rodeheaver GT. Ischemia-reperfusion injury in chronic pressure ulcer formation: a skin model in the rat. Wound Repair Regen 2000;8:68-76.

30.

Ahn ST , Mustoe TA. Effects of ischemia on ulcer wound healing: a new model in the rabbit ear. Ann Plast Surg 1990;24:17-23.

31.

Liechty KW , Sablich TJ , Adzick NS , et al. Recombinant adenoviral mediated gene transfer in ischemic impaired wound healing. Wound Repair Regen 1999;7:148-153.

32.

Wu L , Mustoe TA. Effect of ischemia on growth factor enhancement of incisional wound healing. Surgery 1995;117:570-576.

33.

Zhao LL , Davidson JD , Wee SC , et al. Effect of hyperbaric oxygen and growth factors on rabbit ear ischemic ulcers. Arch Surg 1994;129:1043-1049.

34.

Pittet B , Chang P , Cederna P , et al. The role of neovascularization in the survival of an arterialized venous flap. Plast Reconstr Surg 1996;97:621-629.

35.

Passaniti A , Taylor RM , Pili R , et al. A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab Invest 1992;67:519-528.

36.

Kleinman HK , McGarvey ML , Hassell JR , et al. Basement membrane complexes with biological activity. Biochemistry 1986;25: 312-318.

37.

Gibson JJ , Sheikh AY , Rollins MD , et al. Increased oxygen tension and wound fluid vascular endothelial growth factor levels. Surg Forum 1998;49:607-610.

38.

Gimbrone M-AJ , Cotran RS , Leapman SB , et al. Tumor growth and neovascularization: an experimental model using the rabbit cornea. J Natl Cancer Inst 1974;52:413-427.

39.

Muthukkaruppan V , Auerbach R. Angiogenesis in the mouse cornea. Science 1979;205:1416-1418.

40.

Lee PC , Salyapongse AN , Bragdon GA , et al. Impaired wound healing and angiogenesis in eNOS-deficient mice. Am J Physiol 1999;277:H1600-H1608.

41.

Ribatti D , Vacca A , Ranieri G , et al. The chick embryo chorioallantoic membrane as an in vivo wound healing model. Pathol Res Pract 1996;192:1068-1076.