Purine Nucleotide Metabolism in the Cat Brain After One Hour of Complete Ischemia

Abstract

—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).

Regional Brain Energy Metabolism after Complete versus Incomplete Ischemia in the Rat in the Absence of Severe Lactic Acidosis

“…Deep halothane anesthesia probably decreased the met abolic rate at the onset of both incomplete and com plete ischemia (Brunner et al, 1971). The magni tude of metabolic changes in complete ischemia is comparable with that reported in the cat and monkey and 1 h of complete ischemia under bar biturate anesthesia (Kleihues et al, 1974(Kleihues et al, , 1975. De spite the fact that the ischemic insult had been uni form, postischemic metabolic recovery after com plete ischemia was regionally different.…”

Adenosine and Neopterin Levels in Cerebrospinal Fluid of Patients with Neurological Disorders.

“…Brain adenosine levels have been shown to rise in the brain interstitial fluid or cerebrospinal fluid (CSF) soon after the onset of total ischemia and hypoxia (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Adenosine in CSFis thought to be responsible for the cerebral vasodilatation which increases CBF,because a ventriculocisternal perfusion of adenosine causes an increase in CBF (14), and because the instillation of adenosine deaminase or a potent adenosine receptor blocker, 8-phenyltheophylline or theophylline into CSFreduces the hypoxic and hypercapnic dilatation or rat pial arterioles or CBF, respectively (3,15).…”

Treatment of Experimental Cerebral Ischemia

“…When the brain tissue is recirculated with blood , the resulting gradients are rapidly equilibrated by passive influx of fluid and sodium from the blood into the brain tissue , causing sudden increase of brain volume and elevation of intracra nial pressure. However , blood recirculation also supplies the brain tissue with glucose and oxygen , and energy-producing metabolism is rapidly re- (Kleihues et al , 1974;Nordstrom et al , 1978a). Tissue osmolality decreases and energy dependent ion exchange pumps are reactivated , re sulting in resolution of post-ischemic brain edema (Hossmann , 1976).…”