Purine nucleoside use as surrogate markers of cerebral ischaemia during local and general anaesthetic carotid endarterectomy

Abstract

Objectives: In periods of cerebral ischaemia, adenosine triphosphate is metabolised, leading to accumulation of adenosine inosine and hypoxanthine. These can be measured in real time using peripheral blood samples intraoperatively. The primary aim of this study was to describe changes in purine concentrations in a cohort of patients undergoing carotid endarterectomy under general anaesthetic, and to evaluate correlation between changes in values with major perioperative steps. The secondary aim was to compare changes in concentrations with a previous cohort of patients who had undergone carotid endarterectomy under local anaesthetic. Methods: This was a prospective observational study. Purine concentrations were determined from arterial line samples and measured via an amperometric biosensor at specific time points during carotid endarterectomy. Mean arterial pressure was manipulated to maintain steady cerebral perfusion pressure throughout the procedure. These results were analysed against data from a cohort of patients who underwent carotid endarterectomy under local anaesthetic in previously published work. Results: Valid results were obtained for 37 patients. Purine concentrations at baseline were 3.02 ± 1.11 µM and 3.16 ± 1.85 µM for the unshunted and shunted cohorts, respectively. There was no significant change after 30 min of carotid clamping at 2.07 ± 0.89 and 2.4 ± 3.09 µM, respectively (both p > 0.05). Peak purine during the clamp phase in the loco-regional anaesthetic cohort was 6.70 ± 3.4 µM, which was significantly raised compared to both general anaesthetic cohorts (p = 0.004). There were no perioperative neurological events in either cohort. Conclusion: This small study does not demonstrate conclusive evidence that purine nucleosides can be used as a marker of cerebral ischaemia; the comparisons to the loco-regional anaesthetic data offer information about differences in the cerebral adenosine triphosphate metabolism between general anaesthetic and loco-regional anaesthetic. We hypothesise that the lack of a rise in purine nucleosides under general anaesthetic may be caused by a decrease in the cerebral metabolic rate and loss of metabolic rate-blood flow coupling caused by general anaesthetic agents.

Elevated blood purine levels as a biomarker of seizures and epilepsy

“…Blood purine concentrations measured 40 min after intra‐amygdala PBS injection in vehicle control mice were 2.32 ± .40 μmol·L –1 . This is similar to data reported previously for normal human blood purine levels using the same detection technology 31 . Induction of SE by intra‐amygdala KA resulted in a rapid two‐ to threefold increase in blood purine concentrations when compared to vehicle‐injected control mice (Figure 1G).…”

“…Purine levels were already increased 0–10 min after the termination of SE by lorazepam (8.93 ± 1.03 µmol·L –1 ) and remained significantly elevated for up to 4 h (9.28 ± 1.71 μmol·L –1 ) when compared to time‐matched vehicle‐injected control mice, returning to baseline levels by 8 h after lorazepam treatment (4.47 ± 1.53 μmol·L –1 ; Figure 1G). Treatment with lorazepam slightly lowered blood purine concentrations in vehicle‐injected control mice (3.43 ± .67 µmol·L –1 [prelorazepam] vs. 1.60 ± .27 µmol·L –1 [1 h postlorazepam], n = 9 [prelorazepam] and n = 5 [postlorazepam], p = .074), demonstrating that lorazepam treatment did not contribute to increased purine concentrations post‐SE and in line with lower blood purine levels found in patients under general anesthesia 31 . ROC analysis determined that blood purine concentration measurements taken within the first 10 min postlorazepam at a cutoff rate of 2.96 µmol·L –1 had the highest sensitivity (97%) and specificity (80%) for differentiating seizing from control mice (Figure 1H).…”

“…This is similar to data reported previously for normal human blood purine levels using the same detection technology. 31 Induction of SE by intra-amygdala KA resulted in a rapid two-to threefold increase in blood purine concentrations when compared to vehicle-injected control mice ( Figure 1G). Purine levels were already increased 0-10 min after the termination of SE by lorazepam (8.93 ± 1.03 µmol•L -1 ) and remained significantly elevated for up to 4 h (9.28 ± 1.71 μmol•L -1 ) when compared to time-matched vehicle-injected control mice, returning to baseline levels by 8 h after lorazepam treatment (4.47 ± 1.53 μmol•L -1 ; Figure 1G).…”

“…Treatment with lorazepam slightly lowered blood purine concentrations in vehicleinjected control mice (3.43 ± .67 µmol•L -1 [prelorazepam] vs. 1.60 ± .27 µmol•L -1 [1 h postlorazepam], n = 9 [prelorazepam] and n = 5 [postlorazepam], p = .074), demonstrating that lorazepam treatment did not contribute to increased purine concentrations post-SE and in line with lower blood purine levels found in patients under general anesthesia. 31 ROC analysis determined that blood purine concentration measurements taken within the first 10 min postlorazepam at a cutoff rate of 2.96 µmol•L -1 had the highest sensitivity (97%) and specificity (80%) for differentiating seizing from control mice (Figure 1H).…”

Ischemia Effect on the Purine Content in the Cortical Substance During the Experiment

“…Как следствие, пурины и их производные широко участвуют в различных биологических процессах, включая иммунные ответы и взаимодействие «хозяинопухоль» [1], а нарушение их обмена связано с прогрессированием рака [2]. Известно, что под влиянием ишемии содержание пуринов в организме изменяется [3][4][5][6]. Следовательно, изучать пурины можно, с одной стороны, в качестве индикатора ишемии и окислительного стресса в тканях, с другой -в качестве индикатора повреждения генетического материала клеток и нарушения способности их к делению.…”