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.