Langenbeck's Archives of Surgery

, Volume 388, Issue 5, pp 281–290 | Cite as

Experimental models to study microcirculatory dysfunction in muscle ischemia–reperfusion and osteomyocutaneous flap transfer

  • Michael D. Menger
  • Matthias W. Laschke
  • Michaela Amon
  • Rene Schramm
  • Henrik Thorlacius
  • Martin Rücker
  • Brigitte Vollmar
Musculoskeletal Soft Tissue Conditioning



During the past decade, experimental studies have provided convincing evidence that microcirculatory dysfunction plays a pivotal role in the manifestation of tissue injury in ischemia–reperfusion and osteomyocutaneous flap transfer. The study of the mechanisms of injury, however, requires sophisticated experimental in vivo models. With the use of microsurgical techniques, osteomyocutaneous flap transfer can successfully be performed in rat hind limbs, allowing in vivo fluorescent microscopic analysis of post-ischemic microcirculatory dysfunction in all tissues involved, including periosteum, striated muscle, subcutis and skin. The drawback of this “acute” model is that the period of analysis is restricted to a few hours only.


To overcome this limitation, the “chronic” dorsal skinfold chamber preparation, containing striated muscle and subcutis, can be used. This model allows one to study microcirculatory dysfunction after both tourniquet-induced and pressure-induced ischemia–reperfusion-induced tissue injury over a period of up to 3 weeks.


With the use of these models, recent investigations have demonstrated that ischemia–reperfusion and osteomyocutaneous flap transfer are associated with capillary perfusion failure (no-reflow), mediated by intravascular hemoconcentration, endothelial swelling and endothelin (ET)-1-mediated microvascular constriction. In addition, post-ischemic reperfusion provokes an inflammatory response (reflow paradox) in post-capillary venules, which is characterized by β2-integrin-mediated and intercellular adhesion molecule (ICAM)-1-mediated leukocyte adhesion and vascular hyperpermeability, which results in interstitial edema formation. Treatment studies have produced evidence that isovolemic hemodilution and heat shock protein induction are successful in ameliorating capillary no-reflow, while blockade of adhesion molecules, inactivation of oxygen radicals and, also, induction of heat shock proteins, are capable of reducing the post-ischemic inflammatory response.


These experimental results not only demonstrate the importance of the use of advanced in vivo methods to delineate pathophysiological mechanisms in complex disease models, but may also provide a basis for potential prospective randomized trials to test the benefit for the patient in the daily clinical routine.


Adhesion Ischemia–reperfusion Leukocyte adhesion Platelet adhesion Apoptosis Lymphatic transport Flap transfer Osteomyocutaneous flaps No-reflow Reflow paradox 


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Michael D. Menger
    • 1
  • Matthias W. Laschke
    • 1
  • Michaela Amon
    • 1
  • Rene Schramm
    • 2
  • Henrik Thorlacius
    • 3
  • Martin Rücker
    • 4
  • Brigitte Vollmar
    • 5
  1. 1.Institute for Clinical and Experimental SurgeryUniversity of SaarlandHomburg/SaarGermany
  2. 2.Department of Thoracic and Cardiovascular SurgeryUniversity of SaarlandHomburgGermany
  3. 3.Department of Surgery, Malmö University HospitalUniversity of LundMalmöSweden
  4. 4.Department of Oral and Maxillofacial SurgeryUniversity of SaarlandHomburgGermany
  5. 5.Department of Experimental SurgeryUniversity of RostockRostockGermany

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