Effect of Renal Ischemia on Anaerobic CO 2 Production by Dog Kidney in vitro ∗

Summary

1) Rates of anaerobic CO₂ production by tissue obtained from dog kidneys with evidence of cortical ischemia have been compared with tissue from non-ischemic kidneys. Anaerobic CO₂ production rate was consistent with the following coupled oxidation-reduction reaction: α-ketoglutarate + oxaloacetate + GDP + P₁ → malate + succinate + CO₂ + GTP. 2) Cortical washed homogenates from non-ischemic kidneys produced 14.6 ± 1.8 μmoles CO₂/100 mg dry wt hr (M ± SE); cortical homogenates of ischemic kidneys yielded 6.0 ± 3.0 μmoles of CO₂ (P<0.05). Similar studies done on slices revealed no such difference between ischemic and non-ischemic kidneys. 3) The activity of α-KG-dehydrogenase was the same in washed cortical homogenates of both ischemic and non-ischemic kidneys. In contrast, malic-dehydrogenase activity was significantly lower in cortical homogenates of ischemic kidneys. 4) Thus, cortical blanching is associated with a specific change in cortical mitochondrial enzymic activity so that both cortex and medullary homogenates have decreased capacities for complete oxidation of substrates. This specific difference in the enzymic activity of mitochondria from the ischemic cortex may explain, in part, the low activity of the above reaction in ischemic cortical homogenates and may be one of the initial metabolic changes which occurs in the ischemic kidney.