A Novel Ex Vivo Energy-Enhanced Hypothermic Preservation of Skin-Containing Composite Tissues

Abstract

The overall objective of this project was to increase composite tissue tolerance to 24 hours of extended cold ischemia time. To achieve this, paired hindlimbs in rats were randomized to receive isolated hypothermic perfusions with either the University of Wisconsin (UW) solution (control), or the UW + ATPv solution (experimental). ATPv are nanoscale fusogenic lipid vesicles encapsulating ATP and capable of delivering ATP directly into the cytosol of cells. Upon completion of the perfusion, hindlimbs were conserved in static cold storage for either 12, 16 or 24 hours before skin and muscles were harvested for viability assessment. The extended cold ischemia times invariably degraded tissue nucleotides and countered the optimum temperature required for enzymatic actions. These effects rendered nucleotide- and enzyme-dependent tests of viability unreliable. Energy enhanced (ATPv) ex vivo hypothermic perfusions extended hindlimb composite tissue tolerance to 24h of cold ischemia without remarkable vascular or muscle damages. The vascular endothelium exhibited the least tolerance to cold ischemia relative to the skeletal muscle and skin. The addition of O2 to the crystalloid perfusion solutions does not enhance composite tissue tolerance to cold ischemia. Linking the subcellular structural changes to the prevailing proteome provided the best muscle viability index after cold ischemia.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2019
Accession Number
AD1092553

Entities

People

  • El Rasheid Zakaria

Organizations

  • University of Arizona

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Allografts
  • Animal Structures
  • Blood Vessels
  • Cells
  • Chemistry
  • Cold Storage
  • Composite Materials
  • Electron Microscopy
  • Health Care
  • Health Services
  • Mass Spectrometry
  • Proteins
  • Skeletal Muscle
  • Surgery
  • Tissues
  • Transplants
  • Vascular Endothelium

Readers

  • Molecular and Cellular Biochemistry
  • Trauma Surgery or Emergency Medicine.

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech