title: Systematic development of cerebral resuscitation after cardiac arrest. Three promising treatments: cardiopulmonary bypass, hypertensive hemodilution, and mild hypothermia.
abstract: Since 1970 we have investigated postischemic anoxic encephalopathy and potential treatments for cerebral resuscitation after cardiac arrest by cardiopulmonary-cerebral resuscitation (CPCR). The post-resuscitation syndrome has been studied at the levels of cell, organ, organism and community. Short-term and long-term models in rats, dogs, and monkeys have been developed, and an international multicenter randomized clinical trial mechanism was established. Clinical studies disproved the 5-min limit of reversible cardiac arrest and yielded other valuable data on treatments and prognostication. Thiopental loading or calcium entry blocker therapy (lidoflazine) gave no significant improvement in patients. Free radical scavengers are under investigation in the laboratory. We hypothesize that post-arrest perfusion failure and necrotizing cascades require etiology-specific combination treatments. Standard (control) therapy in a current dog model of cardiac arrest (no flow) of 12.5-20 min, reperfusion with cardiopulmonary bypass, and intensive care for 72-96 h has consistently resulted in survival with brain damage. After ventricular-fibrillation (VF) arrest of 17 min, moderate hypothermia (28-32 degrees C) inconsistently improved cerebral outcome. After VF arrest of 12.5 min, hypertension plus hemodilution normalized the local (multifocal) cerebral hypoperfusion post-arrest and, again, inconsistently improved cerebral outcome. Additional mild hypothermia (34-36 degrees C), however, consistently improved cerebral outcome, whether induced before or during and after arrest.
authors.affiliation: International Resuscitation Research Center, University of Pittsburgh, PA.
authors.forename: P
authors.initials: P
authors.lastname: Safar
authors.forename: F
authors.initials: F
authors.lastname: Sterz
authors.forename: Y
authors.initials: Y
authors.lastname: Leonov
authors.forename: A
authors.initials: A
authors.lastname: Radovsky
authors.forename: S
authors.initials: S
authors.lastname: Tisherman
authors.forename: K
authors.initials: K
authors.lastname: Oku
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D001925:Brain Damage, Chronic / Q000473:pathology / Q000503:physiopathology*; D002315:Cardiopulmonary Bypass; D004285:Dogs; D004734:Energy Metabolism / Q000502:physiology; D000882:Haplorhini; D006323:Heart Arrest / Q000473:pathology / Q000503:physiopathology*; D006438:Hemodilution; D007036:Hypothermia, Induced; D002534:Hypoxia, Brain / Q000473:pathology / Q000503:physiopathology*; D007427:Intracranial Pressure / Q000502:physiology; D051381:Rats; D012039:Regional Blood Flow / Q000502:physiology; D012151:Resuscitation