Addition of ulinastatin to preservation solution promotes protection against ischemia-reperfusion injury in rabbit lung

Chin Med J (Engl). 2011 Jul;124(14):2179-83.

Abstract

Background: The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose (LPDG), an extracellular-type solution, has been adopted by most lung transplantation centers, due to the experimental and clinical evidences that LPDG is superior to intracellular-type solutions. Ulinastatin has been shown to attenuate ischemia-reperfusion (I/R) injury in various organs in animals. We supposed that the addition of ulinastatin to LPDG as a flushing solution, would further ameliorate I/R lung injury than LPDG solution alone.

Methods: Twelve male New Zealand white rabbits were randomly divided into 2 groups. Using an alternative in situ lung I/R model, the left lung in the control group was supplied and preserved with LPDG solution for 120 minutes. In the study group 50,000 U/kg of ulinastatin was added to the LPDG solution for lung preservation. Then re-ventilation and reperfusion of the left lung were performed for 90 minutes. Blood gas analysis (PaO₂, PaCO₂), mean pulmonary artery pressure (MPAP) and serum TNF-α level were measured intermittently. The pulmonary water index (D/W), tissue myeloperoxidase (MPO) activity, tissue malondialdehyde (MDA) content and morphologic changes were analyzed.

Results: The study group showed significantly higher PaO₂ and lower MPAP at the end of reperfusion. Serum TNF-α level, left lung tissue MPO and MDA in the study group were significantly lower than those in the control group. D/W and pathologic evaluation were also remarkably different between the two groups.

Conclusions: This study indicated that better lung preservation could be achieved with the use of an ulinastatin modified LPDG solution. Ulinastatin further attenuated lung I/R injury, at least partly by reducing oxidative reactions, inhibiting the release of inflammatory factors and neutrophils immigration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glycoproteins / pharmacology*
  • Lung / drug effects
  • Lung / metabolism
  • Lung Transplantation
  • Male
  • Organ Preservation Solutions / chemistry
  • Organ Preservation Solutions / pharmacology*
  • Rabbits
  • Random Allocation
  • Reperfusion Injury / prevention & control*

Substances

  • Glycoproteins
  • Organ Preservation Solutions
  • urinastatin