Concentrations of adenosine and its metabolites in the rat retina/choroid during reperfusion after ischemia.
OBJECTIVE
Little is known about the nature of biochemical disturbances during reperfusion after retinal ischemia. Previous studies have suggested that adenosine is responsible for regulation of retinal blood flow soon after ischemia has ended. Therefore, in this study we measured concentrations of adenosine and its metabolites in the rat retina/choroid after brief (10 min) or prolonged (60 min) periods of ischemia, and the functional consequences of inhibiting adenosine metabolism.


METHODS
Ischemia was produced in anesthetized rats by ligation of the central retinal artery. The eyes were frozen in situ and purine nucleoside concentration was determined by high performance liquid chromatography. The functional effects of pre-ischemic inhibition of xanthine dehydrogenase/xanthine oxidase were assessed by measurement of the electroretinogram before, during, and up to 7 days following 60 min ischemia.


RESULTS
Changes in the concentrations of adenosine and its metabolites were significant early in the reperfusion period, and were greater in magnitude and occurred earlier in prolonged, compared to brief, ischemic periods. Concentrations of adenosine, inosine, and hypoxanthine remained elevated for 30 min following the end of 60 min ischemia, and xanthine concentration was significantly elevated until 60 min after the end of either 10 or 60 min of ischemia. The onset of its peak value after ischemia was delayed in comparison to that of adenosine. Ischemia-evoked increases in xanthine concentration were attenuated by inhibition of adenosine deaminase or xanthine oxidase/xanthine dehydrogenase. Pre-ischemic inhibition of xanthine oxidase/xanthine dehydrogenase by oxypurinol (40 or 80 mg/kg intraperitoneally [IP]) resulted in a significant improvement in recovery of the a and b waves of the electroretinogram in comparison to a saline-treated control group.


CONCLUSIONS
These results indicate that adenosine is a major component of the biochemical changes that occur after retinal ischemia. Long-lasting increases in xanthine concentration during reperfusion after ischemia could be a source of oxygen free radicals that may contribute to delayed injury of the retina, attempts to decrease xanthine concentration would ideally be initiated within one hour after the end of ischemia.
Roth
S
S
Department of Anesthesia and Critical Care, University of Chicago, IL 60637, USA.
Park
S S
SS
Sikorski
C W
CW
Osinski
J
J
Chan
R
R
Loomis
K
K
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002829:Choroid / Q000378:metabolism*; D004596:Electroretinography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009994:Osmolar Concentration; D010117:Oxypurinol / Q000494:pharmacology; D015649:Pentostatin / Q000494:pharmacology; D011687:Purines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012164:Retinal Diseases / Q000378:metabolism* / Q000503:physiopathology
D004791:Enzyme Inhibitors; D011687:Purines; D015649:Pentostatin; D010117:Oxypurinol; D000241:Adenosine