Abstract
To preserve the disequilibrium between ATP and ADP necessary to drive cellular metabolism, enzymatic pathways rapidly convert ADP to adenosine and the downstream purines inosine and hypoxanthine. During ischaemia, these same pathways result in the production of purines. We performed a prospective observational study to test whether purine levels in arterial blood might correlate with brain ischaemia. We made real-time perioperative measurements, via microelectrode biosensors, of the purine levels in untreated arterial blood from 18 patients undergoing regional anaesthetic carotid endarterectomy. Pre-operatively, the median purine level was 2.4 μM (95% CI 1.3–4.0 μM); during the cross-clamp phase, the purines rose to 6.7 μM (95% CI 4.7–11.5 μM) and fell back to 1.9 μM (95% CI 1.4–2.7 μM) in recovery. Three patients became unconscious during carotid clamping, necessitating insertion of a temporary carotid shunt to restore cerebral blood flow. In these, the pre-operative median purine level was 5.4 μM (range 4.7–6.1 μM), on clamping, 9.6 μM (range 9.4–16.1 μM); during shunting, purines fell to below the pre-operative level (1.4 μM, range 0.4–2.9 μM) and in recovery 1.8 μM (range 1.8–2.6 μM). Our results suggest that blood purines may be a sensitive real-time and rapidly produced indicator of brain ischaemia, even when there is no accompanying neurological obtundation.
Highlights
Cellular metabolism is driven by the disequilibrium between ATP and ADP [1]
When cells are provided with insufficient substrates and/or O2 to make ATP, the enzymatic systems that maximize the disequilibrium between ATP and ADP will rapidly cause the intracellular accumulation of adenosine and downstream purines
We have used a novel biosensor technology to examine the purine levels in sequential arterial blood samples taken before, during and after the mild and reversible brain ischaemia that is imposed during the crossclamp phase of awake carotid endarterectomy
Summary
Cellular metabolism is driven by the disequilibrium between ATP and ADP [1]. While glycolysis and oxidative phosphorylation generate ATP, enzymatic pathways exist in cells to rapidly remove ADP and, in effect, convert it to adenosine and the downstream purines inosine and hypoxanthine. When cells are provided with insufficient substrates (e.g. glucose or lactate) and/or O2 to make ATP, the enzymatic systems that maximize the disequilibrium between ATP and ADP will rapidly cause the intracellular accumulation of adenosine and downstream purines These metabolites can efflux via equilibrative transporters [3] into the extracellular space. We have used a novel biosensor technology to examine the purine levels in sequential arterial blood samples taken before, during and after the mild and reversible brain ischaemia that is imposed during the crossclamp phase of awake carotid endarterectomy This timed, controlled, ischaemic insult to the brain provides an ideal model in which to investigate how rapidly purines are released into the blood following the onset of ischaemia, and how quickly they return to baseline following resolution of the ischemic insult. Once normal neurology was restored, clamps were reapplied allowing a shunt to be inserted before the patient became obtunded a second time [23]
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