title: Bundled postconditioning therapies improve hemodynamics and neurologic recovery after 17 min of untreated cardiac arrest.
abstract: OBJECTIVE
  Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15min of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest.
  
  
  METHODS
  Following 17min of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n=8) or Bundle therapy with stutter ACD CPR+ITD+sevoflurane+P188 (n=12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score.
  
  
  RESULTS
  Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48h), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48h).
  
  
  CONCLUSIONS
  Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17min of untreated cardiac arrest in pigs. All studies were performed with approval from the Institutional Animal Care Committee of the Minneapolis Medical Research Foundation (protocol #12-11).
authors.affiliation: Department of Medicine-Cardiovascular Division, University of Minnesota, United States.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Bartos
authors.affiliation: Department of Integrative Biology and Physiology, University of Minnesota, United States.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Matsuura
authors.affiliation: Department of Medicine-Cardiovascular Division, University of Minnesota, United States.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sarraf
authors.affiliation: Department of Emergency of Medicine, University of Utah, United States.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Youngquist
authors.affiliation: Department of Medicine-Cardiovascular Division, University of Minnesota, United States.
authors.forename: Scott H
authors.initials: SH
authors.lastname: McKnite
authors.affiliation: Department of Medicine-Cardiovascular Division, University of Minnesota, United States.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Rees
authors.affiliation: Department of Medicine-Cardiovascular Division, University of Minnesota, United States.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Sloper
authors.affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, United States.
authors.forename: Frank S
authors.initials: FS
authors.lastname: Bates
authors.affiliation: Department of Medicine-Cardiovascular Division, University of Minnesota, United States.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Segal
authors.affiliation: Department of Medicine-Cardiovascular Division, University of Minnesota, United States; UJF-Grenoble 1/CNRS/CHU de Grenoble/TIMC-IMAG UMR 5525, Grenoble F-38041, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Debaty
authors.affiliation: Department of Medicine-Cardiovascular Division, University of Minnesota, United States.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Lurie
authors.affiliation: Department of Emergency Medicine, University of Michigan, United States.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Neumar
authors.affiliation: Department of Integrative Biology and Physiology, University of Minnesota, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Metzger
authors.affiliation: Department of Anesthesiology, TVHS VA Medical Center, Nashville, TN, United States; Department of Anesthesiology, Vanderbilt University, Nashville, TN, United States.
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Riess
authors.affiliation: Department of Medicine-Cardiovascular Division, University of Minnesota, United States. Electronic address: yanno001@umn.edu.
authors.forename: Demetris
authors.initials: D
authors.lastname: Yannopoulos
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects / Q000379:methods; D003326:Coronary Circulation; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000503:physiopathology; D006323:Heart Arrest / Q000209:etiology / Q000628:therapy; D006439:Hemodynamics; D006801:Humans; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009460:Neurologic Examination; D000077149:Sevoflurane; D013318:Stroke Volume; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000150:complications
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: Cardiac arrest; Cardiopulmonary resuscitation; Poloxamer 188; Postconditioning; Sevoflurane; Ventricular fibrillation