Abstract TP269: Reduction of Human Brain Adenosine Levels Following Remote Ischemic Preconditioning
Introduction: Prior studies demonstrate that ischemic preconditioning (IP) alters adenosine metabolism. The significance of this effect is not fully understood, but evidence suggests that reduction in extracellular adenosine may represent use as an alternative fuel. Transformation into AMP/ADP may also replenish intracellular total adenine nucleotides (TAN), improving the potential high-energy phosphate bonds available in cells facing ischemia. In both cases, adenosine supports cell energy requirements and may be a key component of IP’s protective mechanisms. There are no previous studies of brain adenosine in human patients undergoing remote IP.
Methods: In adults with aneurysmal subarachnoid hemorrhage (SAH), 3-4 remote IP sessions were conducted on non-consecutive days, 4-12 days after hemorrhage. Each session consisted of 4 5-min cycles of lower extremity blood pressure cuff inflation to 30mmHg above systolic blood pressure, followed by 5-min reperfusion. Patients had microdialysis (MD) probes to compare brain adenosine, inosine, xanthine and hypoxanthine before, immediately after, and 24h after RIPC. MD samples from 4 SAH ICU patients without IP were used as controls.
Results: Five RIPC sessions in 3 patients resulted in complete MD data for comparison over time. In all, brain adenosine levels dropped from their baseline (pre-RIPC) level. Average pre-RIPC adenosine went from 19.2 (SD 14.4) fmol/mg to 7.9 (SD 8.6) immediately following the session (p=0.095) and to 3.2 (SD 4.5) by 24h (p=0.048). Adenosine metabolites inosine, xanthine, and hypoxanthine decreased or did not change over the same period, suggesting adenosine consumption rather than non-energy related catabolism. These changes in adenosine were not reflected in CSF levels, which did not change (p=0.5). Brain adenosine in control subjects did not decrease (baseline 0.26±0.17, 24h 6.6±9.3, p=0.27).
Conclusion: Remote IP leads to decreased brain adenosine in SAH patients by 24 hours. Failure to demonstrate a concomitant rise in levels of metabolites suggests that adenosine is consumed by cells in the brain, as previously shown in animal models. This shift toward the energetic metabolism of adenosine may play a key role in the mechanisms of protection induced by IP.
- © 2012 by American Heart Association, Inc.