title: Remote ischemic preconditioning protects the brain against injury after hypothermic circulatory arrest.
abstract: BACKGROUND
  Ischemic preconditioning (IPC) is a mechanism protecting tissues from injury during ischemia and reperfusion. Remote IPC (RIPC) can be elicited by applying brief periods of ischemia to tissues with ischemic tolerance, thus protecting vital organs more susceptible to ischemic damage. Using a porcine model, we determined whether RIPC of the limb is protective against brain injury caused by hypothermic circulatory arrest (HCA).
  
  
  RESULTS
  Twelve piglets were randomized to control and RIPC groups. RIPC was induced in advance of cardiopulmonary bypass by 4 cycles of 5 minutes of ischemia of the hind limb. All animals underwent cardiopulmonary bypass followed by 60 minutes of HCA at 18°C. Brain metabolism and electroencephalographic activity were monitored for 8 hours after HCA. Assessment of neurological status was performed for a week postoperatively. Finally, brain tissue was harvested for histopathological analysis. Study groups were balanced for baseline and intraoperative parameters. Brain lactate concentration was significantly lower (P<0.0001, ANOVA) and recovery of electroencephalographic activity faster (P<0.05, ANOVA) in the RIPC group. RIPC had a beneficial effect on neurological function during the 7-day follow-up (behavioral score; P<0.0001 versus control, ANOVA). Histopathological analysis demonstrated a significant reduction in cerebral injury in RIPC animals (injury score; mean [interquartile range]: control 5.8 [3.8 to 7.5] versus RIPC 1.5 [0.5 to 2.5], P<0.001, t test).
  
  
  CONCLUSIONS
  These data demonstrate 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.
authors.affiliation: Clinical Research Center, Oulu University Hospital, Oulu University, Finland. hanna.alaoja.jensen@gmail.com
authors.forename: Hanna A
authors.initials: HA
authors.lastname: Jensen
authors.forename: Stavros
authors.initials: S
authors.lastname: Loukogeorgakis
authors.forename: Fredrik
authors.initials: F
authors.lastname: Yannopoulos
authors.forename: Eija
authors.initials: E
authors.lastname: Rimpiläinen
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.forename: Hannu
authors.initials: H
authors.lastname: Tuominen
authors.forename: Pasi
authors.initials: P
authors.lastname: Lepola
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Macallister
authors.forename: John E
authors.initials: JE
authors.lastname: Deanfield
authors.forename: Tuomas
authors.initials: T
authors.lastname: Mäkelä
authors.forename: Kirsi
authors.initials: K
authors.lastname: Alestalo
authors.forename: Kai
authors.initials: K
authors.lastname: Kiviluoma
authors.forename: Vesa
authors.initials: V
authors.lastname: Anttila
authors.forename: Victor
authors.initials: V
authors.lastname: Tsang
authors.forename: Tatu
authors.initials: T
authors.lastname: Juvonen
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000209:etiology* / Q000628:therapy*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass / Q000379:methods; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects* / Q000379:methods*; D052279:Creatine Kinase, MB Form / Q000097:blood; D004195:Disease Models, Animal; D004569:Electroencephalography; D006334:Heart Function Tests; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods*; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000209:etiology / Q000628:therapy; D034421:Sus scrofa; D019210:Troponin I / Q000097:blood
chemical_list: D019210:Troponin I; D052279:Creatine Kinase, MB Form