title: Ischemic post-conditioning and vasodilator therapy during standard cardiopulmonary resuscitation to reduce cardiac and brain injury after prolonged untreated ventricular fibrillation.
abstract: OBJECTIVE
  We investigated the effects of ischemic postconditioning (IPC) with and without cardioprotective vasodilatory therapy (CVT) at the initiation of cardiopulmonary resuscitation (CPR) on cardio-cerebral function and 48-h survival.
  
  
  METHODS
  Prospective randomized animal study. Following 15 min of ventricular fibrillation, 42 Yorkshire farm pigs weighing an average of 34 ± 2 kg were randomized to receive standard CPR (SCPR, n=12), SCPR+IPC (n=10), SCPR+IPC+CVT (n=10), or SCPR+CVT (n=10). IPC was delivered during the first 3 min of CPR with 4 cycles of 20s of chest compressions followed by 20-s pauses. CVT consisted of intravenous sodium nitroprusside (2mg) and adenosine (24 mg) during the first minute of CPR. Epinephrine was given in all groups per standard protocol. A transthoracic echocardiogram was obtained on all survivors 1 and 4h post-ROSC. The brains were extracted after euthanasia at least 24h later to assess ischemic injury in 7 regions. Ischemic injury was graded on a 0-4 scale with (0=no injury to 4 ≥ 50% neural injury). The sum of the regional scores was reported as cerebral histological score (CHS). 48 h survival was reported.
  
  
  RESULTS
  Post-resuscitation left ventricular ejection (LVEF) fraction improved in SCPR+CVT, SCPR+IPC+CVT and SCPR+IPC groups compared to SCPR (59% ± 9%, 52% ± 14%, 52% ± 14% vs. 35% ± 11%, respectively, p<0.05). Only SCPR+IPC and SCPR+IPC+CVT, but not SCPR+CVT, had lower mean CHS compared to SCPR (5.8 ± 2.6, 2.8 ± 1.8 vs. 10 ± 2.1, respectively, p<0.01). The 48-h survival among SCPR+IPC, SCPR+CVT, SCPR+IPC+CVT and SCPR was 6/10, 3/10, 5/10 and 1/12, respectively (Cox regression p<0.01).
  
  
  CONCLUSIONS
  IPC and CVT during standard CPR improved post-resuscitation LVEF but only IPC was independently neuroprotective and improved 48-h survival after 15 min of untreated cardiac arrest in pigs.
authors: Cardiovascular Division at The University of Minnesota, MN, United States. yanno001@umn.edu
authors: Demetris
authors: D
authors: Yannopoulos
authors: Nicolas
authors: N
authors: Segal
authors: Timothy
authors: T
authors: Matsuura
authors: Mohammad
authors: M
authors: Sarraf
authors: Marit
authors: M
authors: Thorsgard
authors: Emily
authors: E
authors: Caldwell
authors: Jennifer
authors: J
authors: Rees
authors: Scott
authors: S
authors: McKnite
authors: Karen
authors: K
authors: Santacruz
authors: Keith G
authors: KG
authors: Lurie
mesh_terms: D000241:Adenosine / Q000008:administration & dosage; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000008:administration & dosage; D004195:Disease Models, Animal; D004452:Echocardiography; D004837:Epinephrine / Q000008:administration & dosage; D006323:Heart Arrest / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D057775:Ischemic Postconditioning / Q000379:methods*; D008955:Models, Cardiovascular; D009599:Nitroprusside / Q000008:administration & dosage; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage*; D014693:Ventricular Fibrillation / Q000150:complications*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D000241:Adenosine; D004837:Epinephrine
keywords: Cardiopulmonary resuscitation; Left ventricular function; Neurological function; Post-conditioning; Survival
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