Hamamoto, I

Kokudo, K

Starzl, TE

Todo, S

Zhang, S

English

PubMed

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Role of xanthine-oxidase system in mucosal injury after intestinal preservation and transplantation

D-Scholarship@Pitt

Role of Xanthine-Oxidase System in Mucosal Injury After Intestinal Preservation and Transplantation I. Hamamoto. S. Zhang, K. Kokudo. S. Todo. and T.E. Starzl THE XANTHINE-OXIDASE (XO) system has been considered to be involved in warm ischemia-reperfu-sion injury of the small intestinal mucosa. 1 Briefly, during warm ischemia in the small intestine. xanthine dehydroge-nase (XD) is converted to XO, which produces superoxide radicals in the presence of its" substrate (hypoxanthine and xanthine) and oxygen.2 Meanwhile, adenosine triphos-phate (ATP) is degraded and its degradation product. hypoxanthine. accumulates in the mucosal tissue.z Upon reperfusion (rewanning and reoxygenation), the mucosal tissue is damaged by superoxide radicals produced by converted XO, oxygen, and accumulated hypoxanthine.3 In order to examine whether the XO system is the cause of cold ischemia-reperfusion injury, mucosal XD. XO hypox-anthine. and maltase (MAL) (as an index of mucosal injury) were measured in an autotransplantation model of 24-hour preserved canine intestine. MATERIALS AND METHODS Operative procedures were essentially the same as those of Lillehei et aI. 4 Twelve entire small intestines of mongrel dogs were harve'sted and 1 Land 2 L of cold lactated Ringer's (LR) solution was flushed through the superior mesenteric artery (SMA) and lumen, respectively. Six dogs were autotransplanted immediately by end-to-end anastomoses of the SMA and the superior mesen-teric vein (group A). The other six dogs were autotransplanted after preserving the intestine for 24 hours in cold LR solution (group B). Mucosal tissues were taken before and 15,30.60. and 120 minutes after reperfusion, and immediately frozen in liquid nitrogen. MAL activity of the mucosa was measured by the method of Oahlqvist.5 Tissue hypoxanthine concentration was measured by the method of Wynants and Belle6 by high-performance liquid chromatography (HPLC) equipped with a reverse phase column. Mucosal tissues of before and I hour after reperfusion were used for XO and XO measurements by the method of Wajner.7 RESULTS MAL activity, which indicates the integrity of the mucosa. was maintained within normal range during cold preserva-tion in both groups (group A = 221 and group B = 158 nmoVminimg protein). However, MAL activity in group B animals decreased to 53.8 nmollminimg protein until 60 minutes after graft revascularization, whereas MAL activ-ity of group A remained unchanged. There was no conversion of XD to XO, even after 24-hour cold preservation (Fig l). Perfusion of group A grafts caused no changes to XD and XO; however, XD and XO decreased 17% and 47%, respectively, in group B grafts, possibly by severe mucosal damage. Hypoxanthine concentration doubled immediately after cold flushing, and remained elevated during the 24-hour cold preservation period (Fig 1). Transplantation Proceedings. Vol 25. No 1 (February). 1993: p 1681 c 4 C ~ 'Qj , " -!. 0 ! 3 .. Q.S Cl E • :3 Q 2 )( ~ go Ii s:; ~ ~ .:; " ;: '8 u « Q Fig 1. XD and XO. and hypoxanthine concentration. during 24-hour cold ischemia and 1-hour repertusion .• P < .05 vs normal control; P < .05 vs 0 hours. SUMMARY Preservation of grafts for 24 hours caused severe mucosal damage after reperfusion as demonstrated by the decrease of MAL activity. However, neither XD-to-XO conversion nor hypoxanthine accumulation was detected during 24-hour cold preservation. These results indicate that super-oxide radicals from the XO system are not responsible for intestinal cold ischemia-reperfusion injury. REFERENCES I. Granger ON. Rutili G. McCord JM: Gastroenterology 81:22. 1981 2. Schoenberg MH. Fredholm BB. Haglund U. et aI: Acta Physiol Scand 124:581. 1985 3. Grisham MS, Hernandez LA, Granger ON: Am J Physiol 251:0567, 1986 4. Lillehei RC. Goott B. Miller FA: Ann Surg 150:543. 1959 5. Dahlqvist A: Anal Biochem 22:99. 1968 6. Wynants J. van BeUe H: Anal Biochem 144:258, 1985 7. Wajner M. Harkness RA: Biochim Biophys Acta 991:79. 1989 From the Pittsburgh Transplant Institute, University of Pitts-burgh, Pittsburgh, Pennsylvania. Supported by research grants from the Veterans Administration and Project Grant No OK 29961 from the National Institute of Health. Bethesda, Maryland. Address reprint requests to Thomas E. Starzl. MD, PhD, Pitts-burgh Transplant Institute. University of Pittsburgh, 5C Falk Clinic. 3601 Fifth Ave. Pittsburgh. PA 15213. © 1993 by Appleton & Lange 0041 -13451931$3.001 +0 1681 

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Role of xanthine-oxidase system in mucosal injury after intestinal preservation and transplantation

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