Abstract
Background. The failure of composite flaps despite anastomotic patency is thought to be mediated
by the inflammatory response within the microvasculature, which results from unavoidable
surgical trauma and transfer-related ischemia-reperfusion. Evidence suggests that
stress conditioning may improve flap survival; however, the molecular mechanisms of
protection are far from being clear. Therefore, we analyzed whether stress conditioning-induced
heat-shock protein 32 is effective to prevent the inflammatory response in transferred
osteomyocutaneous flaps. Methods. In a rat model, leukocyte-endothelial cell interaction and endothelial integrity
disruption as early indicators of the inflammatory response were quantitatively analyzed
in muscle, subcuticular tissue, and periosteum of microvascularly transferred osteomyocutaneous
flaps by using intravital fluorescence microscopy. Twenty-four hours before flap transfer,
stress conditioning was induced by local heating of the left hindlimb up to 42.5°C
for 30 minutes. In additional animals, stress conditioning-induced activity of heat-shock
protein 32 was inhibited by tin protoporphyrin-IX. Unconditioned flaps served as controls.
Results. In all tissues analyzed, control flaps showed significant leukocyte adherence in
postcapillary venules, increased intercellular adhesion molecule-1 (ICAM-1) expression,
and endothelial integrity disruption, but a lack of heat-shock protein 32. In contrast,
stress conditioning induced marked heat-shock protein 32 expression, which was associated
with a significant reduction (P <.05) of leukocyte adherence, ICAM-1 expression, and
endothelial hyperpermeability. The inhibition of heat-shock protein 32 by tin protoporphyrin-IX
completely abolished the stress conditioning-induced amelioration of the inflammatory
response in all tissues analyzed. Conclusions. Stress conditioning by local heat-shock priming reduces the inflammatory response
in osteomyocutaneous flaps. The protective effect is predominantly mediated by the
induction of heat-shock protein 32. (Surgery 2001;129:292-301.)
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Article info
Publication history
Accepted:
August 20,
2000
Footnotes
☆Supported by a grant from the Deutsche Forschungsgemeinschaft (Me 900/1-31-4).
☆☆Reprint requests: Michael D. Menger, MD, Institute for Clinical and Experimental Surgery, University of Saarland, D-66421 Homburg/Saar, Germany.
★Surgery 2001;129:292-301.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
