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Biomedical subjects

M J Halsey

Publications and source records attributed to M J Halsey.

At least 55 records · Page 3Linked to original sources
PubMed1989

Cochlear degeneration in minipigs after repeated hyperbaric exposures.

Auditory function and cochlear pathology were investigated in 4 minipigs subjected to compression to 4 ATA, held for 1 h, and decompressed using a standard schedule (Blackpool Tables) on 21 occasions. Three minipigs were used as controls. Brainstem auditory evoked response testing was carried out after the last hyperbaric exposure and showed no response bilaterally in 3 and unilaterally in 1 of the test animals. Light microscopy demonstrated a loss of hair cells throughout the cochlea in all the compressed animals; in one the tectorial membrane was detached and adherent to Reissner's membrane. Vestibular changes were confined to the saccule. Hemorrhage was not a prominent feature. On scanning electron microscopy the pathologic changes included missing hair cells and fused and giant stereocilia. Possible causes of the pathology include barotrauma or direct effects of repeated compression and decompression on the inner ear, or both. The compression-decompression profile used was one that is thought to be safe for compressed air workers who are repeatedly exposed to hyperbaric conditions.

Animals↗
PubMed1988

Anticonvulsant profile of the dihydropyridine calcium channel antagonists, nitrendipine and nimodipine.

The effects of the dihydropyridine calcium channel antagonists, nitrendipine and nimodipine, on convulsions produced by different mechanisms have been studied in rats. Nitrendipine and nimodipine significantly raised the thresholds to pentylenetetrazol for up to six hours after their injection. The calcium channel agonist, BAY K 8644, lowered the convulsion threshold to pentylenetetrazol and antagonised the effects of nitrendipine. In contrast, the severity of seizures produced by N-methyl-dl-aspartate (NMA) was increased by nitrendipine. BAY K 8644 also slightly increased the effects of NMA. Nimodipine and nitrendipine caused small, but significant, increases in the threshold pressures for the convulsions caused by raising the atmospheric pressure with helium gas. The compounds had no effect on strychnine convulsions. The conclusion is that the calcium channel antagonists are anticonvulsant against only certain types of convulsions, such as pentylenetetrazol and high pressure (and ethanol withdrawal, reported previously). Others may be increased, such as NMA seizures, or unaffected, such as strychnine-induced convulsions.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Lack of correlation between the anaesthetic and anti-convulsant potencies of althesin, ketamine and methohexitone.

Using Sprague-Dawley rats, the anti-convulsant potencies of Althesin, ketamine and methohexitone were determined for bicuculline-and strychnine-induced seizures and compared with their effects on hyperbaric seizures. All three anaesthetics protected against both types of chemical convulsants; the degree of protection varied from 34 to 151%, with Althesin being the most effective. However, there was no correlation between their anti-convulsant and anaesthetic potencies, and no relationship between the effects on chemical convulsions and the interactions of the same agents with hyperbaric convulsions. These data suggest that the order of anti-convulsant potencies at equivalent anaesthetic concentration is Althesin much greater than ketamine = methohexitone, and that neither bicuculline-nor strychnine-induced seizures are a good model for hyperbaric convulsions.

Alfaxalone Alfadolone Mixture↗
PubMed1988

Effects of the calcium channel activator Bay K 8644 on general anaesthetic potency in mice.

1. The effects of the calcium channel activator, Bay K 8644, on the anaesthetic potencies of ethanol, argon and pentobarbitone were examined in mice. 2. Bay K 8644, at 1 mg kg-1 i.p., significantly antagonized the general anaesthetic potencies of ethanol and argon, but at 5 and 10 mg kg-1 this compound increased the general anaesthetic potency of these drugs. 3. At doses of 1, 5 and 10 mg kg-1 Bay K 8644 antagonized the anaesthetic effects of pentobarbitone. Bay K 8644, at the highest dose used, did not alter the brain concentrations of pentobarbitone or the blood concentrations of ethanol. 5. The effects of the different doses of Bay K 8644 on the actions of ethanol and of argon are compatible with the known partial agonist properties of this compound on calcium channels in vitro. 6. The actions of Bay K 8644 on the anaesthetic effects of pentobarbitone suggests that specific interactions may be involved in the anaesthetic actions of this compound.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

The effect of two novel dipeptide antagonists of excitatory amino acid neurotransmission on the high pressure neurological syndrome in the rat.

Intracerebroventricular injection in the rat of beta-D-aspartyl aminomethylphosphonate (Asp-Amp) 1 mumol, or Y-D-glutamylaminomethylsulphonate (GAMS) 1 mumol, increases the onset pressure for the initial tremor phase of the high pressure neurological syndrome (HPNS) by 50%. Asp-Amp also significantly increases the onset pressures for myoclonus and for tonic-clonic seizures. GAMS did not significantly change the onset pressures for myoclonus or tonic clonic seizures, but it caused the appearance of brief clonic seizures prior to the onset of the HPNS.

Animals↗
PubMed1987

Serum fluoride levels in morbidly obese patients: enflurane compared with isoflurane anaesthesia.

Obese patients are known to metabolise anaesthetic agents more than patients of normal weight. The extent of this was investigated by the measurement of serum fluoride concentrations in 10 morbidly obese patients undergoing gastroplasty. Five were allocated to receive enflurane and five to receive isoflurane supplemented anaesthesia. The mean peak serum fluoride concentrations after enflurane anaesthesia were greater (22.7 mumol/litre, SE 2.9) than after isoflurane anaesthesia (6.5 mumol/litre, SE 0.6). The mechanisms and implications of this finding are discussed.

Adult↗
PubMed1987

Effect of exposing mice to 50 ATA helium pressure at different stages of pregnancy.

Pregnant T-O mice were exposed to 50 ATA He-O2 pressure for 4 days at different stages of gestation: 4-7, 6-9, and 9-12 days gestation. Controls were exposed to 1 atmosphere absolute (ATA) air. After the exposure period, pregnancy continued until 18 days gestation when the mice were killed and autopsied. Data were collected relating to the litters and placentas (Litter size, percent resorptions, placental weight, fetal-to-placental ratio) and fetuses (weight, crown-rump length, sex, skeletal abnormalities) and analyzed using analysis of variance. Results showed a small but significant increase in the percent resorptions in the pressure group and also a decrease in crown-rump length and placental weight. None of these changes were related to the stage of gestation in which the mice were exposed. No teratogenic effects of pressure were seen. We conclude that exposure to 50 ATA He-O2 during pregnancy in mice produces a small nonselective effect on fetal growth and development but does not affect any specific event taking place during these stages of embryogenesis.

Animals↗
PubMed1986

Calcium channel antagonists decrease the ethanol withdrawal syndrome.

Withdrawal from chronic ethanol intake results in a syndrome of tremor and hyperexcitability, which can progress to seizures and death. Drugs used therapeutically to alleviate the syndrome have sedative actions and dependence liability of their own. The basis of the syndrome is unclear, although ethanol affects many neuronal functions, including membrane calcium conductance. Calcium channel blocking drugs have been used in cardiovascular disorders; they bind to high affinity sites in the brain but have few overt actions on the central nervous system. We have tested the effects of four calcium channel antagonists on the ethanol withdrawal syndrome in rats. Nitrendipine and nimodipine abolished all spontaneous seizures and prevented or reduced seizures following an audiogenic stimulus, and mortality. Verapamil significantly decreased seizure incidence and both it and flunarizine lowered mortality. The dihydropyridines were considerably more effective than diazepam in the withdrawal syndrome but had little effect on pentylenetetrazol seizures, against which diazepam gave good protection. The calcium channel inhibitors showed no sedative activity in normal animals. The results provide evidence that alterations in calcium conductance may be involved in the ethanol withdrawal syndrome and offer possibilities for the development of non-sedative therapeutic treatment of this syndrome.

Animals↗
PubMed1986

Gamma-aminobutyric acid and the high pressure neurological syndrome.

Sodium valproate, nipecotic acid, diaminobutyric acid (DABA) and beta-alanine are drugs which enhance transmission mediated by gamma-aminobutyric acid (GABA) by a variety of mechanisms. They were used to study the role of GABA in the high pressure neurological syndrome (HPNS) in the rat. Sodium valproate, nipecotic acid and DABA reduced the increase in slow waves seen in the electroencephalogram (EEG) of control rats at pressures above 10-20 ATA; however, only sodium valproate had a beneficial effect on the behavioural signs of the high pressure neurological syndrome (tremor, myoclonus and convulsions). Sodium valproate is also thought to decrease neurotransmission produced by excitatory amino acids; thus, these results suggest that GABA is not one of the major neurotransmitters involved in all aspects of the high pressure neurological syndrome and that changes in excitatory neurotransmission may affect the behavioural signs.

Alanine↗
PubMed1986

Folinic acid protection against nitrous oxide teratogenicity in the rat.

The Sprague-Dawley rat was used to demonstrate the effect of nitrous oxide, with and without folinic pretreatment, on reproductive indices and fetal development. One of the objectives of the investigation was to test the hypothesis that at least some of the teratogenic effect of nitrous oxide is related to interference with folate metabolism. Groups of animals were exposed to 70-75% nitrous oxide on day 9 of pregnancy with or without folinic acid 0.1 mg i.p. 12 h before, and immediately before, exposure. Subsequent fetal development was compared with that of various control groups. There were no significant differences in fetal survival, but fetal weights were reduced in both groups exposed to nitrous oxide. Of the indices of skeletal maturity, the number of ossified sternebrae was reduced only in the nitrous oxide group not receiving folinic acid. The incidence of major skeletal abnormalities in the untreated nitrous oxide group was significantly increased to five times that of the control groups, whereas the incidence in the nitrous oxide group receiving folinic acid was not significantly different from control. It is concluded that pretreatment with folinic acid can at least partially reduce the teratogenic effects of nitrous oxide in the rat.

Abnormalities, Drug-Induced↗
PubMed1986

Regional amino acid concentration in the brains of rats exposed to high pressures.

Regional amino acid concentrations were measured in rat brain fixed by microwave irradiation at three levels of elevated atmospheric pressure corresponding to different phases of the high-pressure neurological syndrome [20 atmospheres absolute (ATA), no clinical signs; 60 ATA, tremor; 85 ATA, severe tremor and myoclonic jerks]. No changes in amino acid content occurred at 20 or 60 ATA. At 85 ATA glutamine content increased in hippocampus, striatum, cerebellum, and substantia nigra, and gamma-aminobutyric acid content increased in hippocampus. It is suggested that enhanced glutamate release in various subcortical structures contributes to the myoclonic activity observed at 85 ATA.

Amino Acids↗
PubMed1986

Pressure reversal of alphaxalone/alphadolone and methohexitone in tadpoles: evidence for different molecular sites for general anaesthesia.

Tadpoles were used to study quantitative interactions between high pressure and two intravenous anaesthetics, alphaxalone/alphadolone and methohexitone. The potencies of the two agents were decreased by high pressure but to different extents. The maximum effect was seen in the pressure range 70-130 atmospheres absolute (ATA). The increases in the normobaric anaesthetizing concentration (ED50) required at 100 ATA were alphaxalone/alphadolone:405 +/- 5 (s.d.)%; methohexitone:658 +/- 80 (s.d.)%. For both alphaxalone/alphadalone and methohexitone, the curves obtained when the increase in ED50 was plotted against increasing pressure showed plateaux at pressures above 70 ATA. These data support the concept of the two intravenous drugs causing general anaesthesia by the occupation of separate molecular 'sites' with different but finite capacities.

Amphibians↗
PubMed1986

Hyperbaric-induced subfertility in mice: lack of effect of decompression.

Male mice were exposed to 50 atmospheres absolute (ATA). He for 30 min, twice weekly for 5 wk and their fertility assessed by subsequently mating with untreated virgin females. The exposure schedule was designed to provide compression and decompression times the same as previous positive studies of hyperbaric-induced subfertility but with much shorter periods at maximum pressure (30 min vs. 24 h). We postulated that, if subfertility were associated with exposure to pressure per se rather than with compression or decompression, then the present experiments would fail to produce a decrease in male fertility. The data were compared with those of a control group placed in the hyperbaric chamber at 1 ATA. The pregnancy rate for exposed vs. control mice was 89 vs. 86%, and the mean live liter size was 6.2 vs. 5.6. There were no statistically significant differences between these and other indexes of male fertility, and the results support our hypothesis that the hyperbaric-induced subfertility in male mice is not associated with these decompression procedures.

Animals↗
PubMed1986

Effect of 2-aminophosphonoheptanoic acid on the EEG of rats exposed to high pressure.

Excitatory amino acid neurotransmission may be involved in the tremor component of the high pressure neurological syndrome (HPNS). 2-Amino-7-phosphonoheptanoic acid (2-APH) is a novel antagonist of excitatory amino acids with preferential activity at the N-methyl-D-aspartate receptor. Rats were injected either i.p. or intracerebroventricularly with 2-APH and subsequently exposed to pressure. The EEG changes that occur after treatment with 2-APH at 1 ATA, namely, a marked increase in delta waves (1-4 Hz) in the centro-occipital region, continue at pressure. However, the apparent duration of action of 2-APH is shorter: the power spectra of delta waves reached its maximum value after a mean time of 37 min (SD 12) compared with 60 min (SD 5) in unpressurized rats. Behavioral results include an increase in the onset pressure for tremor--82.6 ATA (SEM 4.7) in treated rats compared with 49.4 ATA (SEM 3.4) in saline controls (P less than 0.005). It is probable that the antitremor effect and the EEG changes resulting from 2-APH are due to decreased postsynaptic activity of an excitatory neurotransmitter, and these data support the hypothesis that tremor may be central rather than peripheral in origin.

2-Amino-5-phosphonovalerate↗
PubMed1986

Effect of barbituric acid on the high pressure nervous syndrome in the rat.

Male Sprague-Dawley rats were compressed in helium-oxygen mixture at a rate of 3 bar/min. Compression ended once the first convulsion was seen. Saline or barbituric acid at 1 or 2% were infused continuously during compression at a rate of 9.49 ml/h (tail vein). With barbituric acid at 1%, coarse tremor and convulsions appeared at higher pressures than in saline controls. No significant change was observed with 2% barbituric acid compared to saline controls. Barbituric acid which is nonanesthetic had some anti-high pressure nervous syndrome (HPNS) activity which is dose dependent. These results suggest that anti-HPNS activity of these different compounds involves at least one site which is different from that responsible for anesthetic activity.

Animals↗