thromboxane-a2 and Brain-Injuries

To examine the levels of thromboxane B2 (TXB2) and 6-keto prostaglandin F1alpha (6-keto PGF1alpha) production in arterial and internal jugular bulb sera in patients with traumatic brain injury (TBI). TBI is associated with arachidonate release and may be associated with an imbalance of vasoconstricting and vasodilating cyclooxygenase metabolites.. A prospective, randomized study.. The intensive care unit of a medical university hospital.. Twenty-six ventilated TBI patents (Glasgow Coma Scale score on admission, < or = 8 points) were divided randomly into two groups: a hypothermic group (n = 15), in which the patients were cooled to 32 to 33 degrees C after being giving vecuronium, midazolam, and buprenorphine; and a normothermic group (n = 11), in which the patients' body temperature was controlled at 36 to 37 degrees C by surface cooling using the same treatment as the hypothermic group. Body temperature control including normothermia was started 3 to 4 hrs after injury. The duration of hypothermia usually lasted for 3 to 4 days, after which the patients were rewarmed at a rate of approximately 1 C per day.. Blood sampling for TXB2 and 6-keto PGF1alpha was started shortly after admission in both groups. Arterial TXB2 levels on admission in both groups were elevated remarkably, but not 6-keto PGF1alpha, thereby causing an imbalance of the prostanoids after injury. In the normothermic group, TXB2 decreased transiently, but this prostanoid increased again 3 days after the injury. In the hypothermic group, such prostanoid differences disappeared shortly after therapy, and the condition was sustained for 10 days. Hypothermia attenuated differences in TXB2 levels between arterial and internal jugular bulb sera, which may reflect reduced cerebral prostanoid production. The Glasgow Outcome Scale score 6 months after the insult in the hypothermic group was significantly higher than that in the normothermic group (p = .04).. The current results from a limited number of patients suggest that moderate hypothermia may reduce prostanoid production after TBI, thereby attenuating an imbalance of thromboxane A2 and prostaglandin I2. However, it must be clarified whether the changes in the prostanoid after moderate hypothermia are a secondary effect of other mediator changes or whether they simply represent an epiphenomenon that is mechanistically unrelated to damage in TBI.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Analgesics, Opioid; Arachidonic Acid; Brain Injuries; Buprenorphine; Child; Child, Preschool; Female; Glasgow Coma Scale; Glasgow Outcome Scale; Humans; Hypnotics and Sedatives; Hypothermia, Induced; Jugular Veins; Male; Midazolam; Middle Aged; Neuromuscular Nondepolarizing Agents; Prospective Studies; Prostaglandin-Endoperoxide Synthases; Thromboxane A2; Time Factors; Treatment Outcome; Vecuronium Bromide

To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period.. Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2.. Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock.

Topics: Animals; Brain; Brain Injuries; Cerebrovascular Circulation; Dogs; Female; Hypotension; Intracranial Pressure; Male; Multivariate Analysis; Shock, Hemorrhagic; Thromboxane A2; Thromboxane B2