Cerebral Vascular and Metabolic Response to Sustained Systemic Inflammation in Ovine Traumatic Brain Injury

Traumatic brain injury (TBI) is frequently accompanied by a systemic inflammatory response secondary to multiple trauma, shock, or infections. This study investigated the impact of sustained systemic inflammation on cerebral hemodynamics and metabolism in ovine traumatic brain injury. Fifteen sheep were investigated for 14 hours. Head injury was induced with a nonpenetrating stunner in anesthetized, ventilated animals. One group (TBI/Endo, n = 6) subsequently received a continuous endotoxin infusion for 12 hours, whereas a second group (TBI, n = 6) received the carrier. Three instrumented animals served as sham controls. Head impact significantly increased intracranial pressure from 9 ± 4 mm Hg to 21 ± 15 mm Hg (TBI/Endo) and from 10 ± 3 mm Hg to 24 ± 19 mm Hg (TBI) (means ± SD). Internal carotid blood flow increased and cerebral vascular resistance decreased (P < 0.05) during the hyperdynamic inflammatory response between 10 and 14 hours in the TBI/Endo group, whereas these parameters were at baseline level in the TBI group. Intracranial pressure remained unchanged during this period, but increased during hypercapnia. The CMRO2, PaCO2, and arterial hematocrit values were identical among the groups between 10 and 14 hours. It is concluded that chronic endotoxemia in ovine traumatic brain injury was associated with cerebral vasodilation uncoupled from global brain metabolism. Different mechanisms appear to induce cerebral vasodilation in response to inflammation and hypercapnia.

[1]  A. Grünert,et al.  The effect of ketamine on intracranial pressure during haemorrhagic shock under the conditions of both spontaneous breathing and controlled ventilation , 2005, Acta Neurochirurgica.

[2]  L. Eng,et al.  Inflammation in Traumatic Brain Injury: Role of Cytokines and Chemokines , 1998, Neurochemical Research.

[3]  P. Vespa,et al.  Assessment of Cerebral Blood Flow by Means of Blood-Flow-Volume Measurement in the Internal Carotid Artery: Comparative Study With a 133Xenon Clearance Technique , 2003, Stroke.

[4]  M. Hart,et al.  Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury , 2003, Journal of Neuroimmunology.

[5]  H. Baba,et al.  Early multiple organ failure after recurrent endotoxemia in the presence of vasoconstrictor-masked hypovolemia* , 2003, Critical care medicine.

[6]  R. Vialet,et al.  Safety of sedation with ketamine in severe head injury patients: Comparison with sufentanil , 2003, Critical care medicine.

[7]  W. Dietrich,et al.  Inflammatory Mechanisms after Ischemia and Stroke , 2003, Journal of neuropathology and experimental neurology.

[8]  P. Tyrrell,et al.  Inflammation and Infection in Clinical Stroke , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[9]  G. Knudsen,et al.  Cerebral Blood Flow and Oxidative Metabolism during Human Endotoxemia , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  J. Hardman,et al.  Pathology of head trauma. , 2002, Neuroimaging clinics of North America.

[11]  H. Aken,et al.  The effects of sepsis on gut mucosal blood flow in rats , 2001, European journal of anaesthesiology.

[12]  M. Rancan,et al.  ROLE OF CEREBRAL INFLAMMATION AFTER TRAUMATIC BRAIN INJURY: A REVISITED CONCEPT , 2001, Shock.

[13]  R. McCarron,et al.  Proinflammatory Cytokine Expression Contributes to Brain Injury Provoked By Chronic Monocyte Activation , 2001, Molecular medicine.

[14]  H. Melzner,et al.  Early inflammatory mediator response following isolated traumatic brain injury and other major trauma in humans , 2001, Langenbeck’s Archives of Surgery.

[15]  A. Faden,et al.  Combined mechanical trauma and metabolic impairment in vitro induces NMDA receptor‐dependent neuronal cell death and caspase‐3‐dependent apoptosis , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  T. Raju,et al.  Correlation of Flow Probe Determinations of Common Carotid Artery Blood Flow and Internal Carotid Artery Blood Flow with Microsphere Determinations of Cerebral Blood Flow in Piglets , 1999, Pediatric Research.

[17]  M. Ogata,et al.  Neuron-specific enolase as an effective immunohistochemical marker for injured axons after fatal brain injury , 1999, International Journal of Legal Medicine.

[18]  M. Booke,et al.  Role of nitric oxide in sepsis-associated pulmonary edema. , 1999, American journal of respiratory and critical care medicine.

[19]  P. Kochanek,et al.  Blood-brain barrier permeability, neutrophil accumulation and vascular adhesion molecule expression after controlled cortical impact in rats: a preliminary study. , 1998, Acta neurochirurgica. Supplement.

[20]  J. Parratt,et al.  Nitric oxide in sepsis and endotoxaemia. , 1998, The Journal of antimicrobial chemotherapy.

[21]  S. Bhagwanjee,et al.  American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definitions of the systemic inflammatory response syndrome and allied disorders in relation to critically injured patients. , 1997, Critical care medicine.

[22]  D. Prough,et al.  Cerebral blood flow during experimental endotoxemia in volunteers. , 1997, Critical care medicine.

[23]  D. Hovda,et al.  Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm. , 1997, Journal of neurosurgery.

[24]  C. Iadecola.  Bright and dark sides of nitric oxide in ischemic brain injury , 1997, Trends in Neurosciences.

[25]  P. Nibbering,et al.  Relation between pro- and anti-inflammatory cytokines and the production of nitric oxide (NO) in severe sepsis. , 1997, Cytokine.

[26]  Christopher J. Brown,et al.  A head impact model of early axonal injury in the sheep. , 1996, Journal of neurotrauma.

[27]  M. Wong,et al.  Inducible nitric oxide synthase gene expression in the brain during systemic inflammation , 1996, Nature Medicine.

[28]  J. Ghajar,et al.  Survey of critical care management of comatose, head-injured patients in the United States. , 1995, Critical care medicine.

[29]  Martin Schoning,et al.  Estimation of Cerebral Blood Flow Through Color Duplex Sonography of the Carotid and Vertebral Arteries in Healthy Adults , 1994, Stroke.

[30]  P. Kochanek,et al.  Effects of neutropenia on edema, histology, and cerebral blood flow after traumatic brain injury in rats. , 1994, Journal of neurotrauma.

[31]  G. Bouma,et al.  Cerebral blood flow, cerebral blood volume, and cerebrovascular reactivity after severe head injury. , 1992, Journal of neurotrauma.

[32]  A. R. Nogare,et al.  Southwestern Internal Medicine Conference: Septic Shock , 1991 .

[33]  G. Bouma,et al.  Relationship between cardiac output and cerebral blood flow in patients with intact and with impaired autoregulation. , 1990, Journal of neurosurgery.

[34]  J. Kovacs,et al.  The cardiovascular response of normal humans to the administration of endotoxin. , 1989, The New England journal of medicine.

[35]  D. Herndon,et al.  Cardiopulmonary responses to continuous administration of endotoxin. , 1988, The American journal of physiology.

[36]  M. McCarron,et al.  Septic Shock , 1964, International anesthesiology clinics.