Allopurinol and N-Acetylcysteine Avoid 60% of Intestinal Necrosis in an Ischemia-Reperfusion Experimental Model J.V. Ferrer, J. Ariceta, D. Guerrero, T. Gomis, M.M. Larrea, E. Bale ´ n, and J.M. Lera I SCHEMIA-REPERFUSION (I-R) is a major problem for intestinal transplantation 1 and is a frequent clinical situation due to vascular disease. 2 Although its physiopa- thology is well known, a treatment able to prevent damage due to I-R has not been described. We have designed an animal study using specific antioxidants with good results: N-acetylcysteine (NAC) and allopurinol (ALP). METHODS Wistar rats (250 to 300 g) were fasted 24 hours and had free access to water. Anesthesia was induced with intramuscular ketamine, atropine, and tranxilium. Intestinal ischemia was achieved by superior mesenteric artery oclusion (1 hour). The bowel was reperfused after clamp removal. Two and a half hours later the animals were killed by exanguination. Intestinal necrosis size and plasma levels of amylase, reduced glutathione (GSH), and malon- dialdehyde (MDA) were measured. GSH and MDA were mea- sured in small bowel, lung, and heart tissue. Myeloperoxidase (MPO) was measured in intestinal and lung tissue. The animals were separated in four groups: control, I-R without treatment, I-R treated with NAC (428 mg/kg per hour IV), and I-R treated with ALP (100 mg/kg per hour IV: 50% dose in ischemia period and 50% in reperfusion period) and I-R treated with NAC + ALP. Student’s t test was used for statistical purposes. RESULTS AND DISCUSSION I-R produced an intestinal necrosis of 19  6.8 cm (n = 12), hyperamylasemia and intestinal, lung, and heart GSH de- crease (Table 1). MPO increased from 0.15  0.07 (n = 9) to 0.24  0.06 (n = 5) (P  .05) in small bowel and from 0.34  0.16 (6) to 1.4  0.70 (6) (P  .01) in lung. The size of intestinal necrosis could be reduced by up to 60% in groups treated with NAC, ALP, and NAC + ALP (data not shown). Other metabolism alterations could not be pre- vented, as shown in Table 1. Although more studies should be done, a clinical trial with NAC and/or ALP intravenously should be considered in intestinal transplantation and in- testinal vascular disease because it seems that intestinal and pulmonary injury might be prevented. 3,4 REFERENCES 1. Cicalese L, Caraceni P, Nalesnik MA, et al: Transplantation 62:161, 1996 2. Haglund U: Gut 1994 3. Koike K: Am J Physiol 1995 4. Haglind E: Circ Shock 1994 From the Department of Surgery and Biochemistry, Hospital de Navarra, Navarra, Spain. Address reprint requests to Dr J.V. Ferrer, c/Premin de Iruna 9, 3e A, 31008 Pamplona, Spain. Table 1. Control I-R I-R/NAC I-R/ALP Necrosis size (cm) — 19  6.8 (12) 9.4  3.5 (7)** 8.3  2.6 (9)** Plasma Amylase 2746  545 (12) 7524  1294 (8)** 4151  843 (8)** 7375  2679 (6)** GSH-plasma (mol/mL) 0.308  0.08 (7) 0.385  0.11 (6) 0.266  0.36 (5) 0.263  0.15 (9) MDA-plasma (mol/mL) 51  3.9 (6) 47  12 (6) 37  2.3 (11) 31  9.3 (9) GSH-Bowel (mol/g) 1.74  0.19 (6) 0.52  0.14 (8)** 0.48  0.10 (7)** 0.40  0.18 (7)** GSH-Lung (mol/g) 1.72  0.14 (5) 0.86  0.13 (7)** 0.77  0.12 (7)* 0.63  0.07 (9)** GSH-Heart (mol/g) 1.68  0.22 (5) 0.88  0.07 (6)** 0.85  0.08 (7)** 1.47  0.05 (9)** *P  .05; **P  .01. 0041-1345/98/$19.00 © 1998 by Elsevier Science Inc. PII S0041-1345(98)00784-2 655 Avenue of the Americas, New York, NY 10010 2672 Transplantation Proceedings, 30, 2672 (1998)