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Increase in pulmonary endothelial permeability to water after cold ischaemia is not secondary to an increase in albumin permeability

Rooney SJ, Levine AJ, Parkes K ,Revell M, Shimada I, Farnetti P, Bonser RS

Cardiothoracic Surgical Unit, Queen Elizabeth Hospital, Birmingham.

Introduction: Oedema formation associated with poor gas exchange, increased pulmonary artery pressure and reduced compliance characterise the ischaemic-reperfusion injury seen in primary graft failure after lung transplantation. Improvements in quality of lung preservation and extension of the safe preservation period have been hampered in part by a lack of detailed understanding of the effects of cold ischaemia and reperfusion upon endothelial permeability. This study investigated the effects of cold ischaemia upon endothelial permeability by measuring the capillary filtration coefficient (Kf), which is a measure of water permeability, and the albumin permeability surface area product (PS).

Methodology: Rat lungs were flushed with University of Wisconsin solution (UW) at 4° C and 20 cm/H20 pressure and then stored at 4° C before measurement of either Kf or PS. The control groups received no flush. Kf (units g/ cm water/min/g wet lung tissue) was measured using a gravimetric technique. The lungs were suspended from a force transducer and subjected to measured hydrostatic stress using L-15 (an iso-osmotic, non-haemic solution) via a pulmonary artery catheter and the weight gain was recorded. Kf was then calculated from rate of weight gain as a function of hydrostatic stress. PS albumin (units cm3 / g wet lung tissue/ min) was measured using a single sample method. The lungs were perfused with a Tris-buffered Albumin solution until an isogravimetric state was reached. The pulmonary vascular endothelium was then exposed to I125 labelled albumin for 3 minutes followed by a 3 minute vascular washout with the original solution. Lung tissue was then analysed by scintillation counting for extravascular I125 labelled albumin and the PS calculated. Kf and PS were studied after 4 and 24 hours of cold ischaemia, Ps was also studied at 7 and 14 hours.

Results – expressed as mean + standard error of the mean

 

 

 

 

 

 

 

 

PS could not be measured at 14 and 24 hours because an isogravimetric state was unachievable, presumably due to an excessively damaged capillary endothelium

Conclusion: After 4 hours of cold ischaemia there was a significant increase in endothelial permeability to water. A significant rise in albumin permeability however was not seen until 7 hours. This suggests that initial increase in water permeability is not due to increase in albumin permeability.

 



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