EFFECT OF ACADESINE TREATMENT ON POSTISCHEMIC DAMAGE TO SMALL-INTESTINE

Hemorrhagic mucosal lesions are produced during intestinal ischemia an d after reperfusion due at least in part to the accumulation and activ ation of polymorphonuclear leukocytes in the tissue. It has been shown in vitro that adenosine is instrumental in attenuating this pathophys iological process. Acadesine [5-amino-4-imidazolecarboxamide (AICA) ri boside], a purine nucleoside analogue, increases the availability of a denosine in the tissue. The aim of the study was therefore to assess t he influence of acadesine treatment on neutrophil accumulation, purine metabolism, and mucosal damage after intestinal ischemia and reperfus ion. Intestinal ischemia was induced in cats by partial occlusion of t he superior mesenteric artery for 2 h. Samples of the small intestine were excised before and at the end of the hypotensive period as well a s 10 and 60 min after reperfusion. Conjugated dienes, myeloperoxidase, and reduced and oxidized glutathione, as well as the purine metabolit es, were determined in the tissue samples. The tissue was also examine d histologically. Six cats received saline, and six cats were treated initially before ischemia with acadesine (2.5 mg/kg body wt iv) over 5 min as a bolus. Thereafter, acadesine (0.5 mg . kg(-1). min(-1) iv) w as given continuously during ischemia and 30 min after reperfusion. Ac adesine treatment significantly attenuated the mucosal lesions seen du ring reperfusion. This improvement was due at least in part to the inh ibition of neutrophil accumulation, as judged by low myeloperoxidase l evels. The prevention of neutrophil activation resulted most likely fr om increased adenosine concentrations in the intestinal tissue in the early reperfusion period. We conclude that the severe postischemic les ions induced by polymorphonuclear leukocytes can be prevented by incre asing adenosine concentrations within the tissue by acadesine therapy.