Enhanced preservation of the ischaemic kidney with inosine.
The function of rat kidneys subjected to 60 minutes of warm ischaemia at body-temperature was notably protected by the prior administration of the purine nucleoside inosine as a 40 mg/ml solution maintained at 37 degrees C. With direct intrarenal arterial perfusion of the kidney at the onset of ischaemia or with intraperitoneal (i.p.) injection 40 minutes before ischaemia, the plasma-creatinine at 24 hours was significantly lower (P less than 0-001) than that of untreated 60-minute-ischaemia controls and not significantly different from that of non-ischaemic unilateral-nephrectomy controls. Intravenous inosine 20 minutes beforehand also afforded significant (P less than 0-01) protection. 7-day survival was 100% in 30 inosine-pretreated rats and 65% in 45 rats with all other types of pre-treatment (P less than 0-001). Although i.p. adenosine was better (P less than 0-05) than no treatment, i.p. inosine was better (P less than 0-02) than i.p. adenosine. Allopurinol, phenoxybenzamine, A.T.P., or cyclic A.M.P. caused no improvement over controls. Kidneys perfused with inosine maintained higher purine-nucleotide levels during ischaemia and rapidly resynthesised A.T.P. when blood-flow was restored in vivo.
D000241:Adenosine / Q000008:administration & dosage; D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000378:metabolism; D000493:Allopurinol / Q000008:administration & dosage; D000818:Animals; D003404:Creatinine / Q000097:blood; D000242:Cyclic AMP / Q000008:administration & dosage; D007288:Inosine / Q000008:administration & dosage / Q000494:pharmacology*; D007511:Ischemia / Q000097:blood; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D016030:Kidney Transplantation; D009926:Organ Preservation; D010477:Perfusion; D010643:Phenoxybenzamine / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D014021:Tissue Preservation; D014022:Tissue Survival / Q000187:drug effects
D010643:Phenoxybenzamine; D007288:Inosine; D000493:Allopurinol; D000255:Adenosine Triphosphate; D003404:Creatinine; D000242:Cyclic AMP; D000241:Adenosine