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Biomedical subjects

D I Barry

Publications and source records attributed to D I Barry.

51 records · Page 3Linked to original sources
PubMed1982

The benzodiazepine/GABA receptor complex during severe ethanol intoxication and withdrawal in the rat.

The benzodiazepine/GABA (gammaaminobutyric acid) receptor complex was investigated during severe ethanol intoxication and withdrawal in the rat. The intragastric intubation technique was used to establish physical ethanol dependence in the animals. Cerebral cortex from male Wistar rats was studied 1) after 3 1/2 days of severe ethanol intoxication, 2) during the ethanol withdrawal reaction and 3) in a control group. The effect of GABA-ergic activation by muscimol and THIP (4,5,6,7-tetrahydroisoxazole(5,4-c)pyridin-3-01) on 3H-diazepam binding was unchanged during ethanol intoxication and withdrawal, as was the affinity constant (KD) and the maximal number of binding sites (Bmax) for 3H-flunitrazepam. In conclusion, the benzodiazepine/GABA receptor complex is unlikely to play any causal part in physical ethanol dependence.

Alcoholic Intoxication↗
PubMed1982

Amphotericin B and the blood-brain barrier to methotrexate.

The permeability of the blood-brain barrier (BBB) to methotrexate, Na+, and Cl- was studied in rats treated with the membrane-active antifungal agent amphotericin B. Enhancement of brain uptake of methotrexate was expected as amphotericin B increases the permeability of lipid membranes, including tumor cell membranes. However, amphotericin B had no effect of the BBB permeability to methotrexate, Na+, and Cl-. This may have been because the amphotericin B acted only on the luminal and not on the abluminal brain capillary membrane, leaving the BBB intact.

Amphotericin B↗
PubMed1981

Cerebral oxygen consumption in the rat: pharmacological stimulation and suppression, role of catecholaminergic mechanisms.

The relationship between cerebral oxygen consumption (CMRO2), cerebral blood flow and arterial CO2 tension was investigated during anaesthesia induced by halothane, pentobarbital, ethanol and nitrous oxide. The results obtained by halothane, pentobarbital and ethanol indicate a relationship between central suppressants and CO2 in decreasing CMRO2. During nitrous oxide anaesthesia, CMRO2 increased with increasing CO2 tension, an effect which could be prevented by beta-adrenergic receptor blockade. This indicates a role of catecholaminergic mechanisms in CMRO2 regulation (as is the case during immobilization stress and ethanol withdrawal) perhaps as a protective measure providing increased energy supply in the central nervous system during conditions of endogenous or exogenous stress.

Adrenergic beta-Antagonists↗
PubMed1981

Insulin increases glucose transfer across the blood-brain barrier in man.

The influence of insulin on unidirectional flux of glucose across the blood-brain barrier and on net uptake of glucose by the brain was investigated in seven fasting patients. The unidirectional extraction, E, of [14C]D-glucose was determined using 36Cl- as an intravascular reference, by the indicator dilution method. 0.4 U insulin/kg body wt was infused intravenously over 30 min while blood glucose was maintained constant by glucose infusion. Six determinations were made in each patient, two before, two during insulin infusion, and two after. In connection with each blood-brain barrier study, arterial and cerebral venous samples were taken for measurement of glucose, oxygen, insulin, K+, and phosphate. Cerebral blood flow (CBF) was measured in each patient. The main finding was an increased extraction of glucose from 14 to 21% and a highly significant increase in unidirectional flux (CBF X unidirectional extraction X arterial glucose concentration) from 0.46 to 0.66 mumol/g X min during insulin infusion (plasma insulin approximately 1,500 microU/ml). The net brain uptake of glucose (CBF X arterio-venous difference for glucose) as unaltered during the investigation period of 45 min, which is too short a time for insulin to penetrate the barrier. It follows that the backflux of glucose from the brain was increased during insulin application. The effect of insulin might be a speeding up of the glucose carrier in analogy to heart muscle.

Biological Transport↗
PubMed1979

Cerebral blood flow and oxygen consumption during ethanol withdrawal in the rat.

The ethanol withdrawal syndrome in man and animals is characterized by signs of CNS hyperactivity although a direct measurement of a physiological variable reflecting this CNS hyperactivity has never been performed in untreated man or in animals. We induced ethanol dependence in the rat by means of intragastric intubation with a 20% w/v ethanol solution, thus keeping the animals in a state of continuous severe intoxication for 3--4 days; during the subsequent state of withdrawal characterized by tremor, rigidity, stereotyped movements and general seizures a 25% increase in cerebral oxygen consumption (CMRO2) could be measured; this increase was not due to catecholamines originating from adrenal medulla as adrenomedullectomized animals showed a similar increase in CMRO2 (28%); the withdrawing animals showed a corresponding cerebral blood flow (CBF) increase. The elevated CMRO2 and CBF could be reduced to normal by administration of a beta-adrenergic receptor blocker (propranolol 2 mg/kg i.v.), and hence the increased CMRO2 during ethanol withdrawal could be related to catecholaminergic systems in the brain, e.g. the noradrenergic locus coeruleus system which is anatomically well suited as a general activating system. This interpretation is supported by the earlier neurochemical finding of an increased cerebral noradrenaline turnover during ethanol withdrawal. The exact mechanism underlying the increased cerebral oxygen consumption during ethanol withdrawal and the effect of propranolol on cerebral function during this condition remains to be clarified.

Adrenal Glands↗
PubMed1979

Cerebrovascular effects of central depressants: a study of nitrous oxide, halothane, pentobarbital and ethanol during normocapnia and hypercapnia in the rat.

The effect of the central depressants nitrous oxide, halothane, pentobarbital and ethanol upon cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2) and cerebral vascular reactivity to carbon dioxide were measured using the rapid and repetitive intraarterial 133Xenon injection technique modified for rat studies. The cerebrovascular resistance (CVR) during normocapnia in the pentobarbital group was significantly higher (P less than 0.01) than in the nitrous oxide group thus indicating a vasoconstrictor effect of pentobarbital that may be clinically important, because the ability of barbiturates to contract vessels in healthy brain regions may partly explain the protective properties of these drugs against cerebral ischemia. The results indicated that pentobarbital and ethanol may act synergistically with carbon dioxide in depressing CMRO2 and cerebral vascular reactivity. Finally, it is concluded that nitrous oxide anaesthesia (70% N2O: 30% O2) is suitable as a reference situation in rat studies of the effect of pharmocological agents on CBF, CMRO2 and cerebrovascular reactivity.

Anesthesia, General↗
PubMed1979

The effect of propranolol on cerebral oxygen consumption and blood flow in the rat: measurements during normocapnia and hypercapnia.

The cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) in the rat during normocapnia and hypercapnia were investigated by means of the intraarterial 133Xenon injection technique; measurements were performed during normocapnia and hypercapnia and the effect of propranolol upon CBF and CMRO2 was studied. The CBF technique applied to rat yield reliable results even in high flow situations. A steady state period of only 10--15 s is all that is necessary to obtain the initial slope of the 133Xenon clearance curve from which CBF is calculated and measurements may be repeated within minutes. Hypercapnia caused an increase in CMRO2 of 35% which confirms the findings of other investigators. The beta-adrenergic receptor blocker propranolol (2 mg per kg i.v.) prevented this increase and could eliminate an increase in CMRO2 already induced; this indicates that CO2 affects adrenergic mechanisms. Although propranolol eliminated the CMRO2 response to hypercapnia, it only reduced the CBF response; this dissociation of CBF and CMRO2 response occurred probably because the beta-receptor blockage only eliminated a CBF increase mediated through an increased CMRO2 (cellular response) whereas a direct CO2 effect upon the arterioles (vascular response) persisted.

Animals↗
PubMed1979

Adaptive changes in cerebral blood flow and oxygen consumption during ethanol intoxication in the rat..

Cerebral blood flow (CBF) and oxygen consumption (CMRO2) were measured during acute and long-term ethanol intoxication in the rat. The purpose was to investigate whether the adaptive changes (development of tolerance) occurring in the CNS during ethanol intoxication were associated with changes in CBF and/or CMRO2. Consistent with other studies we found that acute severe ethanol intoxication (median blood alcohol concentration (BAC = 5.4 mg/ml)) caused a significant decrease in CBF and CMRO2. After 3-4 days of severe intoxication (BAC of 6.6 mg/ml) these physiological variables were less affected indicating that functional tolerance had developed: CMRO2 and CBF during acute ethanol intoxication were 9.3 ml/100 g/min and 60 ml/100 g/min respectively; after the long term intoxication period these variables reached 11.2 ml/100 g/min and 78 ml/100 g/min respectively, i.e. values not significantly lower than those of the control group. After induction of hypercapnia (PaCO2 about 80 mmHg) CBF increased by 360% in the control group; in the acutely intoxicated group CBF increased by only 127% and in the long term intoxicated group by 203% indicating that the cerebrovascular CO2-reactivity had also adapted to the ethanol intoxication. It is concluded that adaptive changes of the CNS to chronic ethanol intoxication comprise alterations in CMRO2, CBF and cerebrovascular reactivity.

Adaptation, Physiological↗
PubMedDate not supplied

Cerebral blood flow during dihydralazine-induced hypotension in hypertensive rats.

The cerebrovascular effects of graded, controlled dihydralazine-induced hypotension were studied in rats with renal hypertension (RHR) and spontaneous hypertension (SHR). Repeated measurements of cerebral blood flow (CBF) were made using the intraarterial 133Xenon injection technique in anaesthetised normocapnic animals. Dihydralazine was administered in single increasing i.v. doses (0.1 to 2 mg/kg), and CBF measured after each dose when a stable blood pressure had been reached. From a resting level of 145 +/- 7 mm Hg in RHR and 138 +/- 11 mm Hg in SHR, mean arterial pressure (MAP) fell stepwise to a minimum of around 50 mm Hg. CBF was preserved during dihydralazine induced hypotension, and remained at the resting level of 79 +/- 13 ml/100 g . min in RHR and 88 +/- 16 ml/100 g . min in SHR. Following 2 hours hypotension at the lowest pressure reached, the rats were sacrificed by perfusion fixation and the brains processed for light microscopy. Evidence of regional ischaemic brain damage was found in 4 of 11 animals: in 2 cases the damage appeared to be accentuated in the arterial boundary zones. Although the lower limit of CBF autoregulation in these rats is around 100 mm Hg during haemorrhagic hypotension, dihydralazine brought MAP to around 50 mm Hg without any concomitant fall in CBF. This was interpreted as being due to direct dilatation of cerebral resistance vessels. The combination of low pressure and direct dilatation may have resulted in uneven perfusion, thus accounting for the regional ischaemic lesions.

Animals↗
PubMedDate not supplied

Chronic antihypertensive treatment in the rat reverses hypertension-induced changes in cerebral blood flow autoregulation.

Cerebral blood flow (CBF) autoregulation was studied in renal hypertensive rats receiving chronic antihypertensive treatment. Young Wistar Kyoto rats (WKY) were made hypertensive by the Loomis procedure i.e. partial infarction of one kidney with contralateral nephrectomy. Systolic tail blood pressure was measured at 2-week intervals throughout the study. After two months, by which time the rats had been severely hypertensive for 5-6 weeks, antihypertensive treatment was begun; reserpine, dihydralazine and hydrochlorothiazide were administered in the drinking water. Blood pressure fell rapidly to normotensive levels and remained so. Following two months of antihypertensive treatment, the lower blood pressure limit of CBF autoregulation was studied during controlled bleeding. In age-matched untreated renal hypertensive WKY, the lower limit of autoregulation was in the mean arterial pressure range 90-109 mm Hg, as compared to 50-69 mm Hg in age-matched normotensive WKY. In contradistinction to the untreated rats, the treated rats had a normal lower limit of autoregulation, i.e. 50-69 mm Hg. It was inferred that the reversal of the functional change in CBF autoregulation reflected reversal of hypertension-induced cerebrovascular hypertrophy/hyperplasia.

Animals↗