Adenine nucleotide degradation in ischemic rabbit lung tissue.
The aim of the study was to determine the pathways and site of adenosine triphosphate (ATP) catabolism during lung ischemia, which thus far are largely unknown. For this purpose we used the isolated rabbit lung. Rabbit lungs were flushed in situ with a modified Krebs-Henseleit solution (60 ml/kg), the deflated heart lung blocks were isolated, immersed in saline solution, and stored at 37 degrees C. In group I (normothermic ischemia; n = 6) tissue content of ATP decreased progressively from 9.42 +/- 0.58 mumol/g dry wt to 3.42 +/- 0.24 mumol/g dry wt after 30 min of ischemia and further to 0.51 mumol/g dry weight after 4 h. Hypoxanthine was the major catabolite (92% of the nucleoside and purine base fraction at 4 h ischemia). Adenosine did not accumulate (preischemic 0.08 +/- 0.02 mumol/g dry weight vs. 0.13 +/- 0.01 mumol/g dry weight; P > 0.05). AMP accumulated, but also inosine monophosphate (IMP), which was undetectable before ischemia, increased significantly during ischemia. To determine the breakdown pathway of AMP, 400 microM of the adenosine deaminase inhibitor EHNA was added to the flush solution in group II (n = 6). During ischemia, ATP breakdown was unaltered but adenosine became the major catabolite (2.8 times the concentration of hypoxanthine at 4 h ischemia). By pretreatment of the rabbits with the nucleoside transport inhibitor R 75231 (group III; n = 6) no effect was observed on the concentrations during ischemia of inosine and hypoxanthine and only a minor increase of adenosine was found. Cytochemical localization of nucleoside phosphorylase revealed activity predominantly in the endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
De Leyn
P
P
Division of Thoracic Surgery, Catholic University Leuven, Belgium.
Lerut
T
T
Schreinemakers
H
H
van Belle
H
H
Lauwerijns
J
J
van Lommel
F
F
Verbeken
E
E
Flameng
W
W
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D007511:Ischemia / Q000378:metabolism*; D007700:Kinetics; D008168:Lung / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D008954:Models, Biological; D010430:Pentosyltransferases / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors
D000227:Adenine Nucleotides; D011687:Purines; D010430:Pentosyltransferases; C067995:nucleoside phosphorylase