Barbiturates decrease the expression of vascular endothelial growth factor in hypoxic cultures of porcine brain derived microvascular endothelial cells.

Fischer S, Renz D, Schaper W, Karliczek GF.

Max-Planck Institute for Physiological and Clinical Research, Department of Anaesthesiology and Intensive Care, Benekestrasse 2-8, 61231 Bad Nauheim, Germany.

Vascular endothelial growth factor (VEGF) is known to be produced in higher amounts during hypoxia by a variety of cell types and has been shown to increase the permeability of brain derived microvascular endothelial cells (BMEC) during hypoxia by an autocrine mechanism. Because the barbiturates, methohexital (MH) and thiopental (TP), induced a dose-dependent reduction in hypoxia-induced permeability changes of BMEC, the effect of both barbiturates on the VEGF expression during hypoxia was investigated. Both barbiturates decreased the hypoxia-induced expression of VEGF in BMEC in a concentration-dependent manner. This effect is partly caused by the impairment of the hypoxia-induced VEGF mRNA stabilization. VEGF-induced permeability changes during normoxia were unaffected by the barbiturates suggesting that MH and TP are directly reducing hypoxia-induced VEGF synthesis. In conclusion, the inhibiting effect of these barbiturates on the hypoxia-induced VEGF expression results in the decreased permeability of the BMEC monolayer during hypoxia, which may contribute to the described neuroprotective action of barbiturates by reduction of brain edema formation. Copyright 1998 Elsevier Science B.V.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9748518&dopt=Abstract barbiturate Butalbital Fioricet





Comparative effects of hypothermia, barbiturate, and osmotherapy for cerebral oxygen metabolism, intracranial pressure, and cerebral perfusion pressure in patients with severe head injury.

Nara I, Shiogai T, Hara M, Saito I.

Department of Neurosurgery, Kyorin University School of Medicine, Tokyo, Japan.

In order to select the optimal neurointensive treatment for patients with severe head injury and intracranial hypertension, the effects of hypothermia (HT), barbiturates (BT), and osmotic agents (OT) on focal and diffuse cerebral oxygen metabolism were evaluated by means of continuous monitoring of bifrontal regional oxygen saturation (rSO2), jugular bulb oxygen saturation (SjO2), jugular bulb temperature (Tjb), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). PATIENTS AND METHODS: Cerebral oxygen metabolism in SjO2 and rSO2, ICP, CPP, and Tjb were continuously monitored in severe head injury patients with Glasgow Coma Scale < 8, ages 10-62: 13 with focal and 10 with diffuse injuries. The effects of BT (n = 6), HT (n = 9), and OT (n = 8) on these parameters (ICP/CPP, SjO2, and rSO2) were compared. Evaluations were performed in terms of: a) Percentage of abnormal values based on normal control values; ICP < 20 mm Hg, CPP > 60 mm Hg, SjO2 55-75%, and rSO2 60-80% were calculated, b) Effects of pentobarbital dose (mg/kg/h) for the parameters compared among < 1.0, 1.1-2.0, 2.1-3.0, and > 3.1. c) Effects of Tjb (degree C) on parameters compared among hyperthermia (> 38 degrees C), normothermia (36-37.9 degrees C), mild hypothermia (34-35.9 degrees C) and moderate hypothermia (< 33.9 degrees C). RESULTS: a) Abnormal data differed significantly among the three treatment groups. rSO2 showing ischemia on the affected side was more marked in BT than in HT or OT. b) ICP decreases and CPP increases correlated significantly with the pentobarbital dose. c) ICP decreases and CPP increases correlated significantly with decreased Tjb. CONCLUSION: The therapeutic effects of hypothermia, barbiturates, and osmotherapy on cerebral oxygen metabolism and ICP/CPP are different according to the underlying pathological lesions of patients with severe head injury.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9779133&dopt=Abstract barbiturate Butalbital Fioricet





Barbiturates impair astrocyte glutamate uptake.

Swanson RA, Seid LL.

Department of Neurology, Veterans Affairs Medical Center and University of California, San Francisco 94121, USA. ray itsa.ucsf.edu

Barbiturates are widely used as neuroprotective agents during status epilepticus and during surgical procedures that cause cerebral ischemia. The efficacy of this practice is unproved, however, and while barbiturates may counter neuronal excitotoxicity, they can also inhibit mitochondrial ATP production. Since glutamate uptake is energetically costly, mitochondrial inhibition could impair glutamate uptake. To examine this possibility, glutamate uptake was measured in primary rat astrocyte cultures in the presence of several barbiturates. Different barbiturates had differing effects on glutamate uptake at normal glucose concentrations, but all potentiated inhibition of glutamate uptake during glucose deprivation. Thiamylal and thiopental were the most potent barbiturates examined, with 0.3 mM causing approximately 40% reduction in glutamate uptake rates. Barbiturates also potentiated ATP depletion during glucose deprivation, supporting mitochondrial inhibition as the mechanism of these effects. These findings suggest that barbiturates can, under some conditions, impair glutamate uptake at concentrations relevant to their clinical use.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9814816&dopt=Abstract barbiturate Butalbital Fioricet





Automated procedure for determination of barbiturates in serum using the combined system of PrepStation and gas chromatography-mass spectrometry.

Namera A, Yashiki M, Iwasaki Y, Ohtani M, Kojima T.

Department of Legal Medicine, Hiroshima University School of Medicine, Japan.

A system of an automatic sample preparation procedure followed by on-line injection of the sample extract into a gas chromatograph-mass spectrometer (GC-MS) was developed for the simultaneous analysis of seven barbiturates in human serum. A sample clean-up was performed by a solid-phase extraction (SPE) on a C18 disposable cartridge. A SPE cartridge was preconditioned with methanol and 0.1 M phosphate buffer. After loading 1.5 ml of a diluted serum sample into the SPE cartridge, the cartridge was washed with 2.5 ml of methanol-water (1:9, v/v). Barbiturates were eluted with 1.0 ml of chloroform-isopropanol (3:1, v/v) from the cartridge. The eluate (1 microl) was injected into the GC-MS. The calibration curves, using an internal standard method, demonstrated a good linearity throughout the concentration range from 0.1 to 10 microg ml(-1) for all barbiturates extracted. The proposed method was applied to 27 clinical serum samples from three patients who were administrated secobarbital.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9824230&dopt=Abstract barbiturate Butalbital Fioricet