thromboxane-b2 and Seizures

The objectives of this study were to evaluate the possible mechanisms involved in prolongation of bleeding time in pre-eclamptic patients receiving a magnesium sulfate infusion to prevent convulsions. Eighteen pre-eclamptic patients near term or at term (4 cases 33 to 35 weeks; the remainder > 36 weeks) were studied. Fifteen of them received magnesium sulfate infusion; 3 did not and served as controls. Bleeding time (modified Ivy method with Surgicutt), platelet count, platelet aggregation pattern, as well as serum arachidonic acid metabolites [thromboxane B2 (TxB2) and 6-Keto-prostaglandin F1 alpha (6-Keto-PGF1 alpha)] werde done on admission to the labor floor (before magnesium infusion) and repeated at discontinuation of the infusion, 12-24 hours postpartum; the controls received the second test 24 hours postpartum. Thirteen of 15 patients receiving magnesium sulfate had an increase in bleeding time from an average of 6 minutes 31 seconds to 11 minutes 56 seconds, an 82% rise (p < 0.004). In 2 there was a decrease. Among the 3 controls the averages were 6 minutes 38 seconds and 6 minutes 3 seconds. The total magnesium given ranged from 52.5 to 145 grams. Platelet counts averaged 251,000/mm3 (range 145,000-519,000). Platelet aggregation pattern done in 11 patients and was normal and unchanged after magnesium in 10 of the patients with increased bleeding time and one control. TxB2 and 6-Keto-PGF1 alpha levels did not change significantly either after magnesium administration (688 and 135 pgm/ml, to 654 and 117) or in controls (695 and 230 pgm/ml, to 445 and 225). Likewise, the ratio of these 2 substances did not change in either group (6.3 to 6.6, and 4.2 to 2.2). There was no correlation between duration of infusion or total magnesium given and directions of small changes observed. This study confirms a prior preliminary observation that magnesium sulfate infusion, as currently used to prevent eclamptic convulsions, induces a significant prolongation of bleeding time. This effect is mediated neither by changes in platelets count or aggregation pattern, nor by changing the level or ratios of serum arachidonic acid metabolites (TxB2 and 6-Keto-PGF1 alpha). Further studies are needed to clarify the mechanism of this clinically important observation of increased bleeding following magnesium sulfate infusion.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Bleeding Time; Female; Gestational Age; Humans; Magnesium Sulfate; Platelet Aggregation; Platelet Count; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy; Seizures; Thromboxane B2

Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) levels were measured in rats following experimental traumatic brain injury. Rats (n = 36) were prepared for fluid percussion brain injury under pentobarbital anesthesia. Twenty-four hours later, rats were lightly anesthetized using methoxyflurane, injured (2.3 atm), and killed 5 or 15 min later. Twelve of the rats died before and are not included in the analyses. The following groups were used for data analysis: group I (n = 6) were sham-injured rats prepared for injury but not injured: group II (n = 6) were injured and killed 5 min later; group III (n = 12) were injured and killed 15 min posttrauma. Thirty seconds prior to sacrifice by decapitation into liquid nitrogen, all rats were injected with indomethacin (3 mg/kg, intravenously [IV]) to prevent postmortem PG synthesis. After sacrifice, brains were removed, weighed, and homogenized in a small quantity of phosphate buffer with indomethacin (50 micrograms/ml). PGE2 and TxB2 levels were determined using double-label radioimmunoassays. Posttraumatic convulsions were observed in 5 of 12 rats in group III and these rats were analyzed separately. PGE2 and TxB2 levels increased significantly (p less than 0.05) in both hemisphere and brainstem 5 min posttrauma. Fifteen minutes after injury, both PGE2 and TxB2 levels remained elevated but the levels were lower than at 5 min in the rats that did not exhibit posttraumatic seizures. This decrease in PG levels at 15 min was not observed in the rats that had seizures after injury and both PGE2 and TxB2 levels remained high in hemispheres and brainstem. Thus, fluid percussion brain injury results in substantial elevations in PGE2 and TxB2 levels and posttraumatic seizures exacerbate the observed increases.

Topics: Animals; Brain Injuries; Male; Prostaglandins E; Rats; Rats, Inbred Strains; Seizures; Thromboxane B2

The effect of inhibiting endogenous brain thromboxane (TXB2) on pentylenetetrazole-induced seizures was studied using the thromboxane synthetase inhibitors OKY-1581 (20 mg/kg) and UK 38,485 (50 mg/kg). Both compounds selectively decreased (greater than 90%) TXB2 production in brain measured after 2 min of convulsive activity but had no effect on brain PGE2, PGF2 alpha, or 6-keto-PGF1 alpha. No effect of these agents on the tonic seizure threshold was observed, whereas 10 mg/kg ip indomethacin, an agent which inhibits both TXB2 and prostaglandin production, reduced the tonic seizure threshold from 78 +/- 2.6 mg/kg in controls to 62 +/- 3.7 mg/kg. Thus, this study concludes that the availability of TXB2 with convulsant activity is unlikely to be a factor in altering tonic seizure activity observed with indomethacin.

Topics: Animals; Brain; Brain Chemistry; Female; Imidazoles; Indomethacin; Methacrylates; Mice; Pentylenetetrazole; Prostaglandins; Seizures; Thromboxane B2; Thromboxanes

Basal levels of 5 cerebral prostanoids (PGD2, PGF2 alpha, PGE2, 6-keto-PGF1 alpha and thromboxane/TX/B2) were measured radioimmunologically in normal and convulsion-prone gerbils. Significantly less PGD2,PGE2 and 6-keto-PGF1 alpha was found in the brain of seizure-sensitive animals. After treatment with indomethacin, which reduced the amount of brain cyclo-oxygenase products, also normal gerbils exhibited convulsions following environmental stress. The results are in accordance with the hypothesis that endogenous prostanoids play a role in the regulation of seizure susceptibility.

Topics: Alprostadil; Animals; Brain; Brain Chemistry; Dinoprost; Dinoprostone; Disease Susceptibility; Female; Gerbillinae; Male; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Prostaglandins D; Prostaglandins E; Prostaglandins F; Seizures; Thromboxane B2

Administration of convulsant doses of pentetrazole induced an increase of PGF2 alpha, PGE2 and TXB2 immuno-reactive material in mouse brain in vivo. The non-steroidal anti-inflammatory drugs indomethacin, flurbiprofen and diclofenac in equipotent doses inhibited the convulsion-induced increase of prostaglandins and thromboxane B2 (P less than 0.01). The same drugs also lowered the LD50 of pentetrazole (P less than 0.05) and accelerated the onset of tonic seizures evoked by pentetrazole (P less than 0.05). Ibuprofen in a submaximal centrally effective dose acted in the same way on cerebral PG and TXB2 synthesis and on the LD50 of pentetrazole but failed to influence significantly the latency time to the onset of pentetrazole-induced tonic seizures. Aspirin (100 mg/kg) and paracetamol (30 mg/kg), which were without effect on cerebral PG and TXB2 concentrations following pentetrazole-induced seizures, were also ineffective in lowering the convulsive threshold and the LD50 of pentetrazole. It is concluded that non-steroidal anti-inflammatory drugs act on the convulsive threshold by inhibition of cerebral prostaglandin and/or thromboxane synthesis.

Topics: Animals; Anti-Inflammatory Agents; Brain; Male; Mice; Pentylenetetrazole; Prostaglandins E; Prostaglandins F; Seizures; Thromboxane B2

Topics: Animals; Brain; Brain Ischemia; Cerebral Cortex; Convulsants; Fatty Acids, Essential; Gerbillinae; Hypoxia; Probenecid; Prostaglandins; Prostaglandins F; Rats; Seizures; Thromboxane B2

The amount of free arachidonic acid and prostaglandin F2 alpha in rat cerebral hemispheres was increased following convulsions induced by carbachol and metrazol. The level of thromboxane B2 was not affected and prostaglandin endoperoxides could only be "trapped" after a very short convulsive period. Unesterified fatty acid levels at 2 minutes post-mortem were decreased by 50% in the cerebral hemispheres of phenytoin treated rats. Under the same conditions, phenobarbital and diazepam had little effect on the levels of free fatty acids in rat brain.

Topics: Animals; Brain; Carbachol; Fatty Acids, Nonesterified; Male; Pentylenetetrazole; Prostaglandin Endoperoxides; Prostaglandins F; Rats; Seizures; Thromboxane B2; Thromboxanes