Abstract 2594: Remote Ischemic Preconditioning Protects the Brain Against Injury Following Hypothermic Circulatory Arrest
Ischemic preconditioning (IPC) is an innate mechanism that protects tissues from injury during ischemia and reperfusion. IPC has systemic effects that protect tissues remote from those undergoing preconditioning (remote IPC; RIPC). RIPC can be elicited by applying brief periods of ischemia to tissues with ischemic tolerance (skeletal muscle) yet protect vital organs that are more susceptible to ischemic damage. Using a porcine model, we determined if RIPC of the limb is protective against brain injury caused by hypothermic circulatory arrest (HCA). 12 piglets were randomized to control and RIPC groups before undergoing cardiopulmonary bypass (CPB) and 60 minutes HCA at 18oC. RIPC was induced by 4 cycles of 5-minute ischemia alternating with reperfusion of the hind limb (inflation of pneumatic cuff to 200mmHg) prior to CPB. Intracranial pressure and temperature, brain lactate concentration and electroencephalographic (EEG) activity were monitored for 8 hours after HCA. Assessment of neurological status was performed daily for 7 days post-operatively, using a species-specific quantitative behavioral score. All animals were sacrificed and brain tissue was harvested for histopathological analysis. Data were analyzed using 2-way ANOVA or student’s t-test. Study groups were balanced for baseline and intra-operative parameters; no differences were observed in intracranial pressure and temperature. Brain lactate concentration was significantly lower (p<0.0001, ANOVA) and recovery of EEG activity faster (p<0.05, ANOVA) in the RIPC group compared to control. RIPC had a beneficial effect on neurological function during the 7-day follow-up period (behavioral score; p<0.0001 vs. control, ANOVA). Histopathological analysis demonstrated a significant reduction in total cerebral injury in RIPC animals compared to controls [injury score; median (interquartile range): control 6.4 (5.0 – 8.0) vs. RIPC 1.6 (0.5–2.5), p<0.001, t-test]. These data demonstrate, for the first time, that RIPC protects the brain against HCA-induced injury, resulting in accelerated recovery of neurological function. RIPC might be neuroprotective in patients undergoing surgery with HCA and improve long-term outcomes. Clinical trials to test this hypothesis are warranted.