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Pronlonged hypothermic machine perfusion preserves hepatocellular function but potentiates endothelial cell
Hongzhi Xu1, Charles Y Lee, Mark G Clemens
1Department of Biology, University of North Carolina, Charlotte, NC 28223, USA.
Transplantation
|June 18, 2004
Summary
Extended hypothermic machine perfusion (HMP) may preserve liver hepatocyte function but can impair endothelial cell function, leading to organ damage upon reperfusion. This suggests endothelial health is critical for successful HMP liver preservation.
Area of Science:
- Organ transplantation research
- Surgical innovation
- Biomedical engineering
Background:
- Hypothermic machine perfusion (HMP) offers advantages for liver preservation, expanding donor availability.
- Current HMP technology faces challenges in maintaining optimal liver function during extended preservation.
- Investigating endothelial and hepatocellular integrity post-HMP is crucial for refining preservation protocols.
Purpose of the Study:
- To evaluate the impact of extended HMP (>24 hours) on rat liver endothelial and hepatocellular functions.
- To compare HMP with simple cold storage (SCS) for liver preservation beyond 24 hours.
- To identify potential mechanisms of organ injury following extended HMP.
Main Methods:
- Rat livers underwent 24-hour HMP using University of Wisconsin (UW) solution or 24-hour SCS.
- Livers were reperfused, and hepatocyte function was assessed via lactate dehydrogenase (LDH) release, bile production, and indocyanine green (ICG) uptake.
- Sinusoidal endothelial cell (SEC) function and permeability were evaluated using hyaluronic acid (HA) uptake and the multiple indicator dilution (MID) method.
Main Results:
- HMP livers exhibited better initial hepatocyte function (lower LDH, higher bile flow, greater ICG uptake) compared to SCS livers after 24 hours.
- Post-reperfusion, HMP livers showed significantly higher LDH levels, increased endothelial permeability, and reduced HA uptake than SCS livers.
- Greater liver edema was observed in HMP livers compared to SCS livers, as indicated by wet/dry weight ratios.
Conclusions:
- Extended HMP (24 hours) may preserve initial hepatocyte function but can induce endothelial cell dysfunction.
- Endothelial cell dysfunction during cold preservation appears to be a key factor in subsequent hepatocyte dysfunction and cell death upon reperfusion.
- Optimizing HMP strategies to protect sinusoidal endothelial cells is essential for improving outcomes in extended liver preservation.