title: Ablation of free radical-mediated reperfusion injury for the salvage of kidneys taken from non-heartbeating donors. A quantitative evaluation of the proportion of injury caused by reperfusion following periods of warm, cold, and combined warm and cold ischemia.
abstract: Postischemic renal failure is a severe problem following cadaveric renal transplantation, especially if the kidney has been harvested from a non-heartbeating donor, and thereby subjected to periods of both warm and cold ischemia. It is well established that a substantial component of postischemic injury is produced by oxygen-derived free radicals generated from xanthine oxidase at reperfusion. However, the clinical potential of free radical ablative therapy is dependent upon the proportion of the total injury caused by this reperfusion mechanism, compared with the proportion resulting from ischemic injury per se. Therefore, we quantitatively evaluated these proportions in porcine kidneys subjected to various periods of warm (renal artery occlusion in situ), cold (harvest, cold preservation, and allotransplantation), and combined warm and cold ischemia. Experiments were paired, one kidney treated with either superoxide dismutase (SOD) or allopurinol for free radical ablation, the contralateral kidney serving as a control. Creatinine clearance (Ccr) was measured separately for each kidney 48 hr after reperfusion. After 1 and 2 hr of warm ischemia, Ccr dropped to 50% and 36% of normal, respectively. This was improved to 110% and 55% when SOD was given into the renal artery at reperfusion. Similarly, after 24 and 48 hr of cold ischemia, kidney function was significantly improved from 30% and 18% to 72% and 47% of normal, respectively, when allopurinol was added to the preservation solution. SOD used at harvest and again at reperfusion was particularly effective following combined warm and cold ischemia, in a situation mimicking the harvest of cadaver kidneys from a non-heartbeating donor. These findings suggest that the ablation of free radical-mediated reperfusion injury may improve posttransplant renal function sufficiently to allow expansion of the cadaveric donor pool to include non-heartbeating donors.
authors.affiliation: Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
authors.forename: T
authors.initials: T
authors.lastname: Hoshino
authors.forename: W R
authors.initials: WR
authors.lastname: Maley
authors.forename: G B
authors.initials: GB
authors.lastname: Bulkley
authors.forename: G M
authors.initials: GM
authors.lastname: Williams
mesh_terms: D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D003080:Cold Temperature; D005609:Free Radicals; D006324:Heart Arrest, Induced / Q000379:methods; D006358:Hot Temperature; D007511:Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D007668:Kidney / Q000098:blood supply; D016030:Kidney Transplantation; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion / Q000009:adverse effects* / Q000379:methods; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D005609:Free Radicals; D000493:Allopurinol; D013482:Superoxide Dismutase