The effect of acadesine treatment on postischemic damage to the small intestine. Schoenberg, M. H., B. Poch, D. Moch, M. Marzinzig, E. Marzinzig, T. Mattfeldt, H. Gruber, H. G. Beger. Department of General Surgery, University of Ulm, Ulm, FRG, Institute of Pathology, University of Ulm, Ulm, FRG, Gensia Inc., La Jolla, USA
APStracts 2:0259H, 1995.
Hemorrhagic mucosal lesions are produced during intestinal ischemia and after reperfusion due at least in part to the accumulation and activation of polymorphonuclear leukocytes in the tissue. It has been shown in vitro that adenosine is instrumental in attenuating this pathophysiological process. Acadesine (5-amino-4-imidazole carboxamide riboside, AICA riboside) a purine nucleoside analogue increases the availability of adenosine in the tissue. The aim of the study was therefore to assess the influence of acadesine treatment on neutrophil accumulation, purine metabolism and mucosal damage after intestinal ischemia and reperfusion. Intestinal ischemia was induced in cats by partial occlusion of the superior mesenteric artery for two hours. Samples of the small intestine were excised before and at the end of the hypotensive period as well as 10 minutes and 60 minutes after reperfusion. Conjugated dienes, myeloperoxidase, reduced and oxidized glutathione as well as the purine metabolites were determined in the tissue samples. The tissue was also examined histologically. Six cats received saline while again six cats were treated initially before ischemia with 2.5 mg/kg b.w. acadesine over 5 minutes i.v. as a bolus, thereafter acadesine was given in a dosage of 0.5 mg/kg/min continuously i.v. during ischemia and 30 minutes after reperfusion. Acadesine treatment significantly attenuated the mucosal lesions seen during reperfusion. This improvement was due at least in part to the inhibition of neutrophil accumulation as judged by low myeloperoxidase levels. The prevention of neutrophil activation resulted most likely from increased adenosine concentrations in the intestinal tissue in the early reperfusion period. We conclude that the severe postischemic lesions which are induced by polymorphonuclear leukocytes can be prevented by increasing adenosine concentrations within the tissue by acadesine therapy. 

Received 19 August 1994; accepted in final form 4 May 1995.
APS Manuscript Number H712-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  6 July 1995.