The mechanism of action of retrograde oxygen persufflation in renal preservation.
Vascular perfusion of gaseous oxygen has been used to prolong the in vitro survival of a number of isolated organs, and has been shown to improve the hypothermic preservation of ischemically injured kidneys that were subsequently transplanted. We have investigated the mechanism of this effect. Rabbit kidneys were subjected to 60 min of warm ischemia prior to preservation for 24 hr with Ross, Marshall, and Escott's hypertonic citrate solution, with or without retrograde oxygen persufflation (ROP) via the renal vein. It was found that adenine nucleotide levels were almost doubled in the ROP-preserved kidneys, principally due to higher adenosine triphosphate (ATP) concentrations. It was shown that cytochrome oxidase activity was unaffected by ischemia or preservation method, but studies with the metabolic inhibitors ouabain and a mixture of cyanide and iodoacetate suggested that ATP was being synthesized during the storage period but was also being utilized to power the active volume-regulating pump. Morphological examination revealed a much greater degree of cell swelling and cytological injury in the kidneys not subject to ROP, and the interstitial space appeared much reduced in the latter group. At the ultrastructural level, the ROP-treated kidneys showed generally well-preserved mitochondria, mostly in the energized "orthodox" configuration. In contrast, the mitochondria in the nonpersufflated kidneys were generally in the "condensed" deenergized state. We conclude that the provision of sufficient oxygen by ROP allows the continued production of ATP in sufficient quantities to permit improved maintenance of cellular volume and morphology under the conditions of low-temperature storage that we have studied.
Pegg
D E
DE
MRC Medical Cryobiology Group, University Department of Surgery, Cambridge, United Kingdom.
Foreman
J
J
Hunt
C J
CJ
Diaper
M P
MP
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D003486:Cyanides / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007668:Kidney / Q000033:anatomy & histology / Q000502:physiology; D007672:Kidney Cortex / Q000648:ultrastructure; D016030:Kidney Transplantation; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D008928:Mitochondria / Q000648:ultrastructure; D009926:Organ Preservation / Q000379:methods*; D010042:Ouabain / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage*; D010477:Perfusion; D011817:Rabbits
D000227:Adenine Nucleotides; D003486:Cyanides; D007461:Iodoacetates; D010042:Ouabain; D003576:Electron Transport Complex IV; D010100:Oxygen; D019807:Iodoacetic Acid