title: The impact of hypercarbia on the evolution of brain injury in a porcine model of traumatic brain injury and systemic hemorrhage.
abstract: Carbon dioxide is perhaps the most potent available modulator of cerebrovascular tone and thus cerebral blood flow (CBF). These experiments evaluate the impact of induced hypercarbia on the matching of blood flow and metabolism in the injured brain. We explore the hypothesis that hypercarbia will restore the relationship of CBF to metabolic demand, resulting in improved outcome following traumatic brain injury (TBI) and hemorrhage. A behavioral outcome score, hemodynamic, metabolic, and pathologic parameters were assessed in anesthetized and ventilated juvenile pigs. Animals were assigned to either normocarbia or hypercarbia and subdivided into TBI (via fluid percussion) with or without hemorrhage. The experimental groups were TBI; TBI + 40% hemorrhage (40%H); TBI + hypercarbia (CO2); and TBI + 40%H + CO2. Hemorrhaged animals were resuscitated with blood and crystalloid. Hypercarbia was induced immediately following TBI using 10% FiCO2. The normocarbic group demonstrated disturbance of the matching of CBF to metabolism evidenced by statistically significant increases in cerebral oxygen and glucose extraction. Hypercarbic animals showed falls in the same parameters, demonstrating improvement in the matching of CBF to metabolic demand. Parenchymal injury was significantly decreased in hypercarbic animals: 3/10 hypercarbic versus 6/8 normocarbic animals showed cerebral contusions at the gray/white interface (p = 0.05). The hypercarbic group had significantly better behavioral outcome scores, 10.5, versus 7.3 for the normocarbic groups (p = 0.005). The decreased incidence of cerebral contusion and improved behavioral outcome scores in our experiments appear to be mediated by better matching of cerebral metabolism and blood flow, suggesting that manipulations modulating the balance of blood flow and metabolism in injured brain may improve outcomes from TBI.
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, and LeBonheur Children's Medical Center, Memphis, USA. glast0@chmcc.org
authors.forename: T F
authors.initials: TF
authors.lastname: Glass
authors.forename: M J
authors.initials: MJ
authors.lastname: Fabian
authors.forename: J B
authors.initials: JB
authors.lastname: Schweitzer
authors.forename: J A
authors.initials: JA
authors.lastname: Weinberg
authors.forename: K G
authors.initials: KG
authors.lastname: Proctor
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology; D002245:Carbon Dioxide / Q000378:metabolism*; D002302:Cardiac Output / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015600:Glasgow Coma Scale / Q000706:statistics & numerical data; D005947:Glucose / Q000378:metabolism; D006470:Hemorrhage / Q000378:metabolism* / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D007427:Intracranial Pressure / Q000502:physiology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D013552:Swine
chemical_list: D002245:Carbon Dioxide; D019344:Lactic Acid; D005947:Glucose