Effect of acadesine treatment on postischemic damage to small intestine.
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-imidazolecarboxamide (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 2 h. Samples of the small intestine were exercised before and at the end of the hypotensive period as well as 10 and 60 min after reperfusion. Conjugated dienes, myeloperoxidase, and 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, and six cats were treated initially before ischemia with acadesine (2.5 mg/kg body wt i.v.) over 5 min as a bolus. Thereafter, acadesine (0.5 mg.kg-1.min- i.v.) was given continuously during ischemia and 30 min 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Schoenberg
M H
MH
Department of General Surgery, University of Ulm, Germany.
Poch
B
B
Moch
D
D
Marzinzig
M
M
Marzinzig
E
E
Mattfeldt
T
T
Gruber
H
H
Beger
H G
HG
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002415:Cats; D002465:Cell Movement; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D012263:Ribonucleosides / Q000494:pharmacology*
D008054:Lipid Peroxides; D011687:Purines; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D009195:Peroxidase; D005978:Glutathione