PURINE NUCLEOTIDE METABOLISM IN THE CAT BRAIN AFTER ONE HOUR OF COMPLETE ISCHEMIA

—Complete cerebral ischemia was produced in normothermic anaesthetized cats by clamping the innominate and the left subclavian arteries combined with lowering the blood pressure. After 1 h of ischemia, ATP was no longer present in detectable amounts. Total adenine nucleotides were reduced to 34 per cent of the normal level. The breakdown of guanine nucleotides was less marked, with small amounts of GTP still being present at the end of the ischemic period. In animals with signs of functional recovery after 3–7 h of recirculation, ATP was resynthesized to 62 per cent of the control level. Total adenine nucleotides increased to 68 per cent and the adenylate energy change—ATP + 1/2 ADP]/AMP + ADP + ATP]—was re-established to within 7 per cent of the pre-ischemic value. Radiochromatography of nucleotides following intravenous injection of ¹⁴C]formate indicated a marked enhancement of postischemic purine de novo synthesis. Purine nucleosides and free bases which accumulated during ischemia, were partially re-utilized by salvage pathways: adenosine was rephosphorylated to AMP by adenosine kinase (EC 2.7.1.20); inosine and hypoxanthine were re-used via IMP in a reaction mediated by hypoxanthine phosphoribosyltransferase (EC 2.4.2.8).