Interstitial brain adenosine and xanthine increase during jugular venous oxygen desaturations in humans after traumatic brain injury

Objective: Adenosine decreases the cerebral metabolic rate for oxygen and i ncreases cerebral blood flow, and it may play an important role in cerebrom etabolic and cerebrovascular responses to hypoperfusion after traumatic bra in injury. Jugular venous oxygen saturation is monitored after traumatic br ain injury to assess brain oxygen extraction, and desaturations may reflect secondary brain insults. We hypothesized that brain interstitial adenosine and related purine metabolites would be increased during jugular venous ox ygen saturation desaturations (<50%) and determined associations between th e purines, lactate, and glucose to assess the role of adenosine during seco ndary insults in humans. Design: Study of critically ill adults with severe traumatic brain injury, Setting: Adult neurointensive care unit. Patients: We prospectively defined periods of normal saturation and desatur ation in six patients after severe traumatic brain injury. Interventions: During these periods, cerebral microdialysis samples of brai n interstitial fluid were collected, and adenosine and purine metabolites w ere measured by high-pressure liquid chromatography, Measurements and Main Results: Adenosine increased 3.1-fold and xanthine in creased 2.5-fold during desaturation periods (both p <.05 vs. normal satura tion period, signed rank). Adenosine, xanthine, hypoxanthine, and cyclic-ad enosine monophosphate correlated with lactate over both study periods (r(2) =.32, .14, .31, .07, and .26, respectively, all p < .05, Pearson product m oment correlation). Conclusion: The marked increases in interstitial brain adenosine that occur during jugular venous oxygen desaturations suggest that adenosine may play an important role during periods of secondary insults after traumatic brai n injury. The correlation of these metabolites with lactate further suggest s that adenosine is increased during periods of enhanced glycolytic metabol ism.