Use of anti-(tumour necrosis factor-alpha) antibody or 3-deaza-adenosine as additives to promote protection by University of Wisconsin solution in ischaemia/reperfusion injury.
Experimental interventions that reduce ischaemia/reperfusion (I/R) lung injury can be used to improve the properties of preservation solutions. We attempted to increase the attenuation of I/R injury by University of Wisconsin solution (UW) by adding an antibody against tumour necrosis factor-alpha (TNF-alpha), to neutralize TNF-alpha, and/or by adding 3-deaza-adenosine (c3-Ado), to inhibit leucocyte adhesion and the biosynthesis of ICAM-1 (intercellular cell-adhesion molecule 1). We examined I/R injury using an isolated rat lung model. Six different solutions were perfused individually, followed by evaluation of I/R injury: (1) 0.9% NaCl (normal saline; NS), (2) NS+anti-TNF-alpha antibody, (3) UW alone, (4) UW+anti-TNF-alpha, (5) UW+c3-Ado and (6) UW+anti-TNF-alpha+c3-Ado. Haemodynamic changes, lung weight gain, capillary filtration coefficient, TNF-alpha levels and lung pathology were analysed in order to evaluate I/R injury. Compared with lungs perfused with NS, lungs treated with NS+anti-TNF-alpha showed less I/R injury. The addition of anti-TNF-alpha and/or c3-Ado to UW reduced I/R injury compared with unmodified UW. Among the six solutions tested, UW containing anti-TNF-alpha antibody reduced I/R injury to the greatest extent. We conclude that addition of anti-TNF-alpha antibody or c3-Ado protects against I/R lung injury when using UW. Further investigation of the improved properties of modified UWs would be beneficial with regard to lung transplantation research.
Chiang
C H
CH
Pulmonary Division, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. chchiang@ndmctsgh.edu.tw
Wu
C P
CP
Perng
W C
WC
Yan
H C
HC
Yu
C P
CP
D000241:Adenosine / Q000737:chemistry; D000493:Allopurinol / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal; D005978:Glutathione / Q000737:chemistry; D006439:Hemodynamics; D007328:Insulin / Q000737:chemistry; D008168:Lung / Q000098:blood supply / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D009924:Organ Culture Techniques; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions / Q000737:chemistry; D009929:Organ Size; D011887:Raffinose / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D014372:Tubercidin; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007328:Insulin; D019188:Organ Preservation Solutions; D014409:Tumor Necrosis Factor-alpha; C055206:University of Wisconsin-lactobionate solution; C018258:3-deazaadenosine; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D014372:Tubercidin; D011887:Raffinose