title: Anaesthetic Postconditioning at the Initiation of CPR Improves Myocardial and Mitochondrial Function in a Pig Model of Prolonged Untreated Ventricular Fibrillation.
abstract: BACKGROUND
  Anaesthetic postconditioning (APoC) attenuates myocardial injury following coronary ischaemia/reperfusion. We hypothesised that APoC at the initiation of cardiopulmonary resuscitation (CPR) will improve post resuscitation myocardial function along with improved mitochondrial function in a pig model of prolonged untreated ventricular fibrillation.
  
  
  METHODS
  In 32 pigs isoflurane anaesthesia was discontinued prior to induction of ventricular fibrillation that was left untreated for 15 min. At the initiation of CPR, 15 animals were randomised to controls (CON), and 17 to APoC with 2 vol% sevoflurane during the first 3 min CPR. Pigs were defibrillated after 4 min of CPR. After return of spontaneous circulation (ROSC), isoflurane was restarted at 0.8-1.5 vol% in both groups. Systolic and diastolic blood pressures were measured continuously. Of the animals that achieved ROSC, eight CON and eight APoC animals were randomised to have their left ventricular ejection fraction (LVEF%) assessed by echocardiography at 4h. Seven CON and nine APoC were randomised to euthanasia 15 min after ROSC to isolate mitochondria from the left ventricle for bioenergetic studies.
  
  
  RESULTS
  ROSC was achieved in 10/15 CON and 15/17 APoC animals. APoC improved haemodynamics during CPR and post-CPR LVEF%. Mitochondrial ATP synthesis, coupling of oxidative phosphorylation and calcium retention capacity were improved in cardiac mitochondria isolated after APoC.
  
  
  CONCLUSIONS
  In a porcine model of prolonged untreated cardiac arrest, APoC with inhaled sevoflurane at the initiation of CPR, is associated with preserved mitochondrial function and improved post resuscitation myocardial dysfunction. Approved by the Institutional Animal Care Committee of the Minneapolis Medical Research Foundation of Hennepin County Medical Center (protocol number 11-05).
authors.affiliation: TVHS VA Medical Center, Nashville, TN, United States; Department of Anesthesiology, Vanderbilt University, Nashville, TN, United States. Electronic address: matthias.riess@vanderbilt.edu.
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Riess
authors.affiliation: Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, United States.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Matsuura
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Minnesota, Minneapolis, MN, United States.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Bartos
authors.affiliation: Departments of Anesthesiology and Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Bienengraeber
authors.affiliation: Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, United States.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Aldakkak
authors.affiliation: Minneapolis Medical Research Foundation, Minneapolis, MN, United States.
authors.forename: Scott H
authors.initials: SH
authors.lastname: McKnite
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Minnesota, Minneapolis, MN, United States.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Rees
authors.affiliation: Department of Emergency Medicine, Medical College of Wisconsin, Milwaukee, WI, United States.
authors.forename: Tom P
authors.initials: TP
authors.lastname: Aufderheide
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Minnesota, Minneapolis, MN, United States.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sarraf
authors.affiliation: Department of Emergency Medicine, University of Michigan Health System, Ann Arbor, MI, United States.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Neumar
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Minnesota, Minneapolis, MN, United States.
authors.forename: Demetris
authors.initials: D
authors.lastname: Yannopoulos
mesh_terms: D000758:Anesthesia / Q000379:methods*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006323:Heart Arrest / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D008929:Mitochondria, Heart / Q000502:physiology*; D012151:Resuscitation / Q000379:methods*; D013552:Swine; D014693:Ventricular Fibrillation / Q000150:complications / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D000777:Anesthetics
keywords: Cardiac arrest; Cardiopulmonary resuscitation; Ischaemia reperfusion injury; Mitochondria; Postconditioning; Sevoflurane