title: Improved neuroprotective effect of methylene blue with hypothermia after porcine cardiac arrest.
abstract: BACKGROUND
  Induced mild hypothermia and administration of methylene blue (MB) have proved to have neuroprotective effects in cardiopulmonary resuscitation (CPR); however, induction of hypothermia takes time. We set out to determine if MB administered during CPR could add to the histologic neuroprotective effect of hypothermia.
  
  
  METHODS
  A piglet model of extended cardiac arrest (12 min of untreated cardiac arrest and 8 min of CPR) was used to assess possible additional neuroprotective effects of MB when administered during CPR before mild therapeutic hypothermia induced 30 min after restoration of spontaneous circulation (ROSC). Three groups were compared: C group (n = 8) received standard CPR; PH group (n = 8) received standard CPR but 30 min after ROSC these piglets were cooled to 34°C; the PH+MB group (n = 8) received an MB infusion 1 min after commencement of CPR and the same cooling protocol as the PH group. Three hours later, the animals were killed. Immediately after death, the brains were harvested pending histological and immunohistological analysis.
  
  
  RESULTS
  Circulatory variables were similar in the groups except that cardiac output was greater in the PH+MB group 2-3 h after ROSC. Cerebral cortical neuronal injury and blood-brain barrier disruption was greatest in the C group and least in the MB group. The neuroprotective effect of MB and hypothermia was significantly greater than that of delayed hypothermia alone.
  
  
  CONCLUSIONS
  Administration of MB during CPR added to the short term neuroprotective effects of induced mild hypothermia induced 30 min after ROSC.
authors.affiliation: Departments of Surgical Sciences/Anesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden. lars.wiklund@surgsci.uu.se
authors.forename: L
authors.initials: L
authors.lastname: Wiklund
authors.forename: F
authors.initials: F
authors.lastname: Zoerner
authors.forename: E
authors.initials: E
authors.lastname: Semenas
authors.forename: A
authors.initials: A
authors.lastname: Miclescu
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.forename: H S
authors.initials: HS
authors.lastname: Sharma
mesh_terms: D000818:Animals; D015415:Biomarkers; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D002540:Cerebral Cortex / Q000473:pathology; D003627:Data Interpretation, Statistical; D005260:Female; D006323:Heart Arrest / Q000628:therapy*; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D018696:Neuroprotective Agents; D010101:Oxygen Consumption / Q000502:physiology; D013534:Survival; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000628:therapy
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D008751:Methylene Blue