Abstract
An in vivo model has been developed for chronic observation of the effects of ischemia on cortical bone remodeling and perfused vascularity. Diaphragm occluders were implanted around the right common iliac artery of four rabbits and inflated to produce 10 h of ischemia to the limb. Microcirculation was monitored with intravital microscopy of injected fluorescent microspheres and FITC-Dextran 70 through a bone window, the tibial bone chamber implant (BCI). Bone resorption and apposition in the BCI were indicated with mineralization dyes. Between 2 and 12 h following release of the occluder, secondary ischemia/no-reflow and other evidence of reperfusion injury were observed. Vessel damage was suggested by abnormally high leakage of FITC-D70 from the few vessels perfused during secondary ischemia. In the weeks following occluder release perfused vasculature increased beyond pre-occlusion levels. Net bone resorption reached a maximum when vascularity passed normal levels. In order to further validate the arterial occlusion model for osteonecrosis, techniques for (1) confirming bone death and (2) detecting increased leukocyte adherence to endothelial cells were added. The dead cell stain Ethidium homodimer-1 was used to tag dead osteocytes immediately after occlusion and produced a measure designated “osteonecrosis index.” To detect leukocytes adhering to vessel walls, carboxyfluorescein diacetate, succinimidyl ester was injected at occluder release. An increase in the number of adherent leukocytes was detected. © 1999 Biomedical Engineering Society.
PAC99: 8764Rr, 8717-d, 8719Tt
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Atsumi, T., and Y. Kuroki. Impairment of the hemodynamics and revascularization in Perthes' disease. In: Bone Circulation and Bone Necrosis, edited by J. Arlet and B. Mazières. New York: Springer-Verlag, 1988, pp. 295–299.
Banzo, J. I., C. de la Fuente, V. Lloréns, J. M. Carril, and C. Arnal. The value of bone scan in Legg-Calvé-Perthes disease. In: Bone Circulation and Bone Necrosis, edited by J. Arlet and B. Mazières. New York: Springer-Verlag, 1988, pp. 247–251.
Carey, L. A., A.-P. C. Weiss, and A. J. Weiland. Quantifying the effect of ischemia on epiphyseal growth in an extremity replant model. J. Hand Surg. 15A:625–630, 1990.
Glas, H. Histomorphologie und morphometrische Analysen der Knochenheilung in einem ''Optical Bone Chamber'' Modell. Gesamten Heilkunde, Vienna: Dissertation, 1997.
Gregg, P. J., and D. W. Walder. Regional distribution of circulating microspheres in the femur of the rabbit. J. Bone Jt. Surg., Br. Vol. 62:222–226, 1980.
Gute, D., and R. J. Korthus. Role of leukocyte adherence in reperfusion-induced microvascular dysfunction and tissue injury. In: Physiology and Pathophysiology of Leukocyte Adhesion, edited by D. N. Granger and G. W. Schmid-Schönbein. Oxford: Oxford Univ. Press, 1995, pp. 359–380.
Jones, J. P. Pathophysiology of osteonecrosis. In: Bone Circulation and Vascularization in Normal and Pathological Conditions, edited by A. Schoutens, J. Arlet, J. W. M. Gardeniers, and S. P. F. Hughes. New York: Plenum, 1993, pp. 249–261.
Jones, J. P. Osteonecrosis and bone marrow edema syndrome: Similar etiology but a different pathogenesis. In: Osteonecrosis, Etiology, Diagnosis and Treatment, edited by J. P. Jones and J. R. Urbaniak. Rosemont: AAOS, 1997, pp. 181–187.
Jones, L. C., and D. S. Hungerford. Models of ischemic necrosis of bone. In: Bone Circulation, edited by J. Arlet, R. P. Ficat, and D. S. Hungerford. Baltimore: Williams & Wilkins, 1984, pp. 30–34.
Kälebo, P., C. Johansson, and T. Albrektsson. Temporary bone ischemia in the hind limb of the rabbit. Acta Orthop. Trauma Surg. 105:321–325, 1986.
Kamler, M., H. Lehr, J. H. Barker, R. K. Saetzler, T. J. Galla, and K. Messmer. Impact of ischemia on tissue oxygenation and wound healing: Intravital microscopic studies on the hairless mouse ear model. Eur. Surg. Res. 25:30–37, 1993.
Kenzora, J. E., R. E. Steele, Z. H. Yosipovitch, and M. J. Glimcher. Experimental osteonecrosis of the femoral head in adult rabbits. Clin. Orthop. Relat. Res. 130:8–46, 1978.
Malizos, K. N., L. D. Quarles, A. V. Seaber, W. S. Rizk, and J. R. Urbaniak. An experimental canine model of osteonecrosis: Characterization of the repair process. J. Orthop. Res. 11:350–357, 1993.
Naito, M., P. L. Schoenecker, J. H. Owen, and Y. Sugioka. Acute effect of traction, compression, and hip joint tamponade on blood flow of the femoral head: An experimental model. J. Orthop. Res. 10:800–806, 1992.
Owen, M., and J. T. Triffitt. Extravascular albumin in bone tissue. J. Physiol. (London) 257:293–307, 1976.
Swiontkowski, M. F., and D. Senft. Cortical bone microperfusion: Response to ischemia and changes in major arterial blood flow. J. Orthop. Res. 10:337–343, 1992.
Winet, H. A horizontal intravital microscope bone chamber system for observing microcirculation. Microvasc. Res. 37:105–114, 1989.
Winet, H., and J. Y. Bao. Microvascular leakage in apposing trabeculae of a healing cortical defect: A bone chamber study in the rabbit tibia. Orthop. Trans. 15:577–578, 1991.
Winet, H., A. Hsieh, and J. Y. Bao. Approaches to the study of ischemia in bone. J. Biomed. Mater. Res. 43:410–421, 1998.
Jones, J. P. Subchondral osteonecrosis can conceivably cause disk degeneration and ''primary'' osteonecrosis. In: Osteonecrosis, Etiology, Diagnosis and Treatment, edited by J. P. Jones and J. R. Urbaniak. Rosemont: AAOS, 1997, pp. 135–142.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hsieh, A.S., Winet, H., Bao, J.Y. et al. Model for Intravital Microscopic Evaluation of the Effects of Arterial Occlusion-caused Ischemia in Bone. Annals of Biomedical Engineering 27, 508–516 (1999). https://doi.org/10.1114/1.194
Issue Date:
DOI: https://doi.org/10.1114/1.194