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1 Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany; Department of Plastic, Reconstructive and Aesthetic Surgery, Inselspital, University of Berne, Berne, Switzerland
2 Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
3 Department of Plastic, Reconstructive and Aesthetic Surgery, Inselspital, University of Berne, Berne, Switzerland
* To whom correspondence should be addressed. E-mail: yvesharder{at}bluewin.ch.
With the use of intravital microscopy in a chronic in vivo mouse model, we studied the demarcation of myocutaneous flaps and evaluated microvascular determinants for tissue survival and necrosis. Chronic ischemia resulted in a transition zone, characterized by a red fringe and a distally adjacent white falx, which defined the demarcation by dividing the proximally normal from the distally necrotic tissue. Tissue survival in the red zone was determined by hyperemia, as indicated by recovery (day-10: 157.6±12.0cm/cm2 vs control: 197.5±20.9cm/cm2; n.s.) of the transiently reduced functional capillary density (day-7: 113.9±33.7cm/cm2 vs 208.0±20.9cm/cm2; p<0.05), and capillary remodeling, including dilation (day-10: 9.97±1.07µm vs 6.38±0.75µm), hyperperfusion (day-10: 9.96±3.60pl/s vs 3.75±0.98pl/s) and increased tortuosity (day-10: 0.82±0.22 vs 0.30±0.05). Angiogenesis and neovascularisation were not observed over the 10-day observation period. The white rim distally to the red zone, appearing as "falx lunatica", showed a progressive decrease of functional capillary density (day-10: 3.8±3.2cm/cm2 (P<0.001)) similar to that of the necrotic distal area, however, without desiccation and thus transparency of the tissue. The development of the distinct zones of the critically ischemic tissue could be predicted by ptO2 analysis already at the time of flap elevation. The "falx lunatica" evolved at a ptO2 between 6.2±1.3mmHg and 3.8±0.7mmHg, while tissue necrosis developed at <3.8±0.7mmHg. Histogical analysis within the "falx lunatica" revealed interstitial edema formation and muscle fiber nuclear rarefaction, however, absence of necrosis. We thus demonstrate that ischemia-induced necrosis does not demarcate sharply from normal tissue, but develops beside a fringe of tissue with capillary remodeling an adjacent "falx lunatica" which survives despite nutritive capillary perfusion failure, probably by direct oxygen diffusion.
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