Protective effects of glycine during hypothermic renal ischemia-reperfusion injury.
The objective of this investigation was to test the effects of glycine, a cytoprotectant in normothermic in vitro models of renal ischemia, in a model of hypothermic renal preservation injury. This study also probes possible physiological mechanisms of glycine protection during renal hypothermic ischemia-reperfusion injury. Canine kidneys were subjected to 48 h of hypothermic ischemia (4 degrees C) after intravascular flush with cold conventional Collins solution (G. H. Collins, M. B. Bravo-Shugarman, and P. I. Terasaki, Lancet 2: 1219-1223, 1969) and were subsequently revascularized for 1 h. After 1 h of reperfusion, glomerular filtration rate, urine production, and electrolyte excretion were dramatically higher when the Collins flush contained 5 mM glycine, compared with the 0 mM glycine controls. Renal tissue adenine nucleotides and glutathione levels progressively declined with graded cold ischemia times, and glycine had no effect on these levels. However, renal tissue ATP levels (but not glutathione) were significantly higher when kidneys were flushed with glycine, stored for 48 h, and reoxygenated in vitro for 1 h at 37 degrees C, compared with kidneys flushed without glycine. Analysis of CoA esters from ischemic renal tissue indicated altered production of only butyryl CoA after 48 and 72 h of cold ischemia, but no differences were detected in glycine or control kidneys. In conclusion, this study reports dramatic functional preservation with glycine in kidneys subjected to hypothermic ischemia and in vivo reperfusion. The mechanisms of these effects appear not to be attributable to the maintenance of cellular adenine nucleotide or glutathione levels nor to the scavenging of accumulated amphipathic acyl CoA esters.
Mangino
M J
MJ
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
Murphy
M K
MK
Grabau
G G
GG
Anderson
C B
CB
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D007035:Hypothermia; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009392:Nephrectomy; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*
D000214:Acyl Coenzyme A; D000227:Adenine Nucleotides; C024343:butyryl-coenzyme A; D000105:Acetyl Coenzyme A; D005978:Glutathione; D005998:Glycine