Post-mortem administration of urokinase in canine lung transplantation from non-heart-beating donors

J Heart Lung Transplant. 2006 Sep;25(9):1148-53. doi: 10.1016/j.healun.2006.07.005.

Abstract

Background: We previously reported that post-mortem heparinization by closed-chest cardiac massage within 30 minutes after cardiac arrest is beneficial in lung transplantation (LTx) from non-heart-beating donors (NHBDs) by preventing formation of microthrombi. In this study, we evaluated the effects of post-mortem administration of urokinase 60 minutes after cardiac arrest.

Methods: Left LTx was performed in 12 pairs of mongrel dogs. Donors were sacrificed and left at room temperature for 2 hours. In Group 1 (n = 6), heparin sodium (1,000 U/kg) was administered intravenously 60 minutes after cardiac arrest, then closed-chest cardiac massage was performed for 1 minute to distribute the heparin. In Group 2 (n = 6), the donors were treated as in Group 1, except, in addition to heparin sodium, urokinase (120,000 U) was administered intravenously before and at the end of cardiac massage. After 2 hours of cardiac arrest, donor lungs were flushed with low-potassium dextran glucose solution. After left LTx, the right pulmonary artery was ligated, and recipients were followed up for 3 hours. Uni- and multivariate repeat analyses were performed to obtain statistical data.

Results: Group 2 had significantly better arterial oxygen tension, lower pulmonary vascular resistance and lower wet/dry weight ratio of the transplanted lung than Group 1. d-dimer level during the warm ischemia was significantly lower in Group 2 than in Group 1.

Conclusions: Post-mortem administration of urokinase along with heparin is beneficial in LTx from NHBDs by fibrinolytic action on already formed pulmonary microthrombi in the cadaver donor lungs.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadaver
  • Dogs
  • Fibrinolysis / drug effects
  • Heart Arrest / physiopathology*
  • Heart Massage
  • Heparin / pharmacology
  • Injections, Intravenous
  • Lung / drug effects
  • Lung / physiology
  • Lung Transplantation / methods*
  • Lung Transplantation / physiology*
  • Organ Preservation / methods
  • Organ Size / drug effects
  • Organ Size / physiology
  • Postmortem Changes
  • Thrombosis / prevention & control
  • Tissue Donors*
  • Urokinase-Type Plasminogen Activator / administration & dosage
  • Urokinase-Type Plasminogen Activator / pharmacology*
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology

Substances

  • Heparin
  • Urokinase-Type Plasminogen Activator