Blood purine measurements as a rapid real-time indicator of reversible brain ischaemia

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.