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 solution (UW) as perfusate has not been well studied. Isolated rat lungs were challenged with various periods of ischaemia and/or reperfusion. Haemodynamics, 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 permeability type of pulmonary oedema, as reflected by increases in LWG and K(fc). LWG and K(fc) in the I(45)R(60)(UW) group (45 min of ischaemia followed by 60 min of reperfusion with UW) were only 2% and 5% respectively of those in the I(45)R(60)(NS) group (where NS is normal saline). LWG and K(fc) in the UW group had both increased by 180 min, to values similar to those in the I(45)R(60)(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 NS in delaying LWG. For longer ischaemic times only, or the same period of ischaemia followed by longer reperfusion periods, greater lung 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 tissue. A significant correlation was obtained between TNF-alpha concentration and LWG. TNF-alpha production in the I(45)R(60)(UW) group was only 7% of that in the I(45)R(60)(NS) group. However, TNF-alpha mRNA expression in the I(45)R(60)(UW) group was 80% of that in the I(45)R(60)(NS) group. This indicates that transcription/translation do not correlate well with cytokine production, and also 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 caused a permeability-type pulmonary oedema that was associated with leucocyte infiltration and the up-regulation of various cytokines, regardless of the perfusion fluid. Except for pulmonary hypertension, less severe I/R lung injury and delayed cytokine production in lungs perfused with UW, the pattern of injury associated with I/R challenge was similar to that in lungs perfused with NS. We propose that more or long-acting protective agents are required as additives in order to modify UW to produce an optimal preservation solution.
Chiang
C H
CH
Division of Pulmonary Immunology and Infectious Disease, Chest Department, Taipei Veterans General Hospital, National Yang-Ming University, No. 201, Section 2, Shih-Pai Road, Taipei, Taiwan, ROC. chiang01@vghtpe.gov.tw
Yu
C P
CP
Wu
C P
CP
Yan
H C
HC
Perng
W C
WC
D000241:Adenosine / Q000494:pharmacology*; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D008297:Male; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D016133:Polymerase Chain Reaction / Q000379:methods; D011654:Pulmonary Edema / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics; D011887:Raffinose / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D015854:Up-Regulation / Q000187:drug effects*
D016207:Cytokines; D007328:Insulin; D019188:Organ Preservation Solutions; D012333:RNA, Messenger; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose