Cytokine up-regulation in ischaemic/reperfused lungs perfused with University of Wisconsin solution and normal saline

Ischaemia/reperfusion (I/R) lung injury using University of Wisconsin solut ion (UW) as perfusate has not been well studied. Isolated rat lungs were ch allenged with various periods of ischaemia and/or reperfusion. Haemodynamic s, lung weight gain (LWG), capillary filtration coefficient (K-fc), tissue pathology, the concentrations of cytokines in the perfusate, and mRNAs for the various cytokines in the lung tissues were measured. I/R induced a perm eability type of pulmonary oedema, as reflected by increases in LWG and K-f c. LWG and K-fc in the I45R60(UW) group (45 min of ischaemia followed by 60 min of reperfusion with UW) were only 2% and 5% respectively of those in t he I45R60(NS) group (where NS is normal saline). LWG and K-fc in the UW gro up had both increased by 180 min, to values similar to those in the I45R60( NS) group. However, these findings show that UW was remarkably effective at preventing LWG after 60 min of reperfusion, and was more than 3-fold more effective than INS in delaying LWG. For longer ischaemic times only, or the same period of ischaemia followed by longer reperfusion periods, greater l ung injury occurred. I/R lung injury also induced increased concentrations of tumour necrosis factor-alpha (TNF-alpha), interleukin 1 and interleukin 6 in the perfusate, and increased the mRNAs for these cytokines in lung tis sue. A significant correlation was obtained between TNF-alpha concentration and LWG. TNF-alpha production in the I45R60(UW) group was only 7% of that in the I45R60(NS) group. However, TNF-alpha mRNA expression in the I45R60(U W) group was 80% of that in the I45R60(NS) group. This indicates that trans cription/translation do not correlate well with cytokine production, and al so suggests that one reason for the effectiveness of UW in delaying LWG may be because it delays TNF-alpha production. In summary, ischaemia or I/R ca used a permeability-type pulmonary oedema that was associated with leucocyt e infiltration and the up-regulation of various cytokines, regardless of th e perfusion fluid. Except for pulmonary hypertension, less severe I/R lung injury and delayed cytokine production in lungs perfused with UW, the patte rn of injury associated with I/R challenge was similar to that in lungs per fused with NS. We propose that more or long-acting protective agents are re quired as additives in order to modify UW to produce an optimal preservatio n solution.