Brief intermittent reperfusion during renal ischemia: effects on adenine nucleotides, oxidant stress, and the severity of renal failure.
The purpose of this study was to assess how brief periods of intermittent reperfusion (IR) imposed during a renal ischemic insult affect adenine nucleotide/catabolite concentrations, oxidant stress, and the severity of ischemic acute renal failure (IARF). Rats were subjected to 35 minutes of renal pedicle occlusion with or without brief IR periods (total less than or equal to 3 minutes). Adenine nucleotides and their catabolites were measured at the end of ischemia and at 30 minutes of the recovery period. Oxidant stress in the recovery phase was assessed by non-protein-bound sulfhydryl and malondialdehyde (MDA) concentrations. The severity of IARF was quantified at 24 hours by degrees of azotemia and histologic damage. Although IR had no significant impact on end-ischemic ATP concentrations, it did induce profound adenine nucleotide catabolite depletion; the sum of adenosine, inosine, inosine monophosphate, hypoxanthine, and xanthine fell by 78%, compared with control ischemia values (p less than 0.001). The pattern of IR affected the degree of catabolite depletion: dividing a single 3-minute IR period into two 1 1/2-minute segments increased catabolite loss by 45% without affecting adenine nucleotide content. Although adenine nucleotide catabolites can be resynthesized to ATP, IR did not worsen postischemic adenine nucleotide recovery. IR augmented postischemic sulfhydryl depletion by 8% (p less than 0.02). However, lipid peroxidation (as assessed by MDA) did not result and the severity of IARF was not adversely affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Thornton
M A
MA
Department of Medicine, University of Washington, Seattle.
Zager
R A
RA
D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology; D000227:Adenine Nucleotides / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005260:Female; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D010084:Oxidation-Reduction; D011485:Protein Binding; D011684:Purine Nucleosides / Q000378:metabolism; D011688:Purinones / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000227:Adenine Nucleotides; D011684:Purine Nucleosides; D011688:Purinones; D013438:Sulfhydryl Compounds; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate