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Biomedical subjects

D I Graham

Publications and source records attributed to D I Graham.

At least 253 records · Page 14Linked to original sources
PubMed1984

Intracranial haemorrhage induced at arterial pressure in the rat. Part 1: Description of technique, ICP changes and neuropathological findings.

Intracranial haemorrhage was produced in the caudate nucleus or the lateral ventricle of Sprague Dawley Rats by connecting a stereotactically inserted cannula to the femoral artery. Two types of lesion resulted from this type of arterial-pressure haemorrhage: Contained intracerebral haemorrhage (ICH) and Uncontained haemorrhage. When the haemorrhage was uncontained, a large and transient rise in intracranial pressure (ICP) (to 65mmHg mean) was accompanied by a fall in cerebral perfusion pressure. By contrast, with contained intracerebral haemorrhage, the rise in ICP was smaller (to 18mmHg mean) and neuropathological evidence of ischaemic brain damage was found in areas surrounding the clot. This observation suggests that with ICH there may be a local reduction in flow in tissue immediately surrounding the haematoma.

Animals↗
PubMed1984

Intracranial haemorrhage induced at arterial pressure in the rat. Part 2: Short term changes in local cerebral blood flow measured by autoradiography.

The regional distribution of blood flow following intracranial haemorrhage at arterial pressure was measured with the 14C-iodoantipyrine autoradiographic technique in Sprague Dawley Rats. With uncontained haemorrhage, there was a bilateral reduction in cerebral blood flow, associated with a fall in cerebral perfusion pressure. With contained intracerebral haemorrhage there was a profound ipsilateral reduction in flow in the hemisphere adjacent to the haematoma. This study indicates that extensive cerebral ischaemia occurs immediately after an intracerebral haemorrhage, and that this may be the result of compression of the microcirculation.

Animals↗
PubMed1984

Haemodynamic and cerebral effects of ATP-induced hypotension.

Controlled decreases in mean arterial pressure to 20%, 40% and 60% of baseline were produced by the administration of increasing concentrations of adenosine triphosphate (ATP) i.v. in five anaesthetized baboons. Indices of the systemic circulation (arterial pressure, right atrial pressure, pulmonary artery pressures, cardiac output) and of the cerebral circulation (cerebral blood flow, cerebral metabolic rate for oxygen, cerebrovascular reactivity) were obtained as arterial pressure was decreased, and following discontinuation of the infusion of ATP. A neuropathological investigation was undertaken at the end of the experimental procedure. The infusion of ATP produced dose-dependent decreases in systemic vascular resistance and mean arterial pressure (MAP). Cardiac output and stroke volume were maintained close to baseline values, or increased slightly. Cerebral blood flow (CBF) increased initially (48 +/- 4 ml min-1/100 g to 68 +/- 9 ml min-1/100 g) and then decreased progressively as MAP was decreased to 40% and 60% of baseline. Cerebrovascular reactivity was shown to be impaired during, and for up to 90 min following, the administration of ATP. However, there was no morphological evidence of ischaemic cell damage in any animal. Tachyphylaxis was not observed during, and there were no instances of rebound hypertension following, the infusion of ATP. The concentration of uric acid had increased significantly by the 40% decrement in MAP, and remained so 60 min after the restoration of the arterial pressure.

Adenosine Triphosphate↗
PubMed1984

Cerebrovascular aspects of converting-enzyme inhibition I: Effects of intravenous captopril in spontaneously hypertensive and normotensive rats.

The cerebrovascular effects of converting enzyme inhibition were examined in normotensive and hypertensive rats. Cerebral blood flow was measured using the intracarotid 133xenon injection method in halothane/nitrous oxide anaesthetized animals. The main finding was that following intravenous administration of captopril (10 mg/kg), cerebral blood flow autoregulation was markedly altered. Although cerebral blood flow was unchanged from baseline levels, both the lower and upper limits of autoregulation were reset to lower mean arterial pressure and the autoregulatory plateau shortened. The lower limit was shifted 20-30 mmHg, the upper limit 50-60 mmHg, and the plateau shortened by 20-40 mmHg. The effect was interpreted as being a consequence of compensatory autoregulatory constriction of small resistance vessels in the brain following captopril-induced dilatation of large resistance vessels. It was inferred that locally produced angiotensin II might play a role in the resistance of large cerebral arteries.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Cerebrovascular aspects of converting-enzyme inhibition II: Blood-brain barrier permeability and effect of intracerebroventricular administration of captopril.

The blood-brain barrier permeability to captopril, and the cerebrovascular effects of intracerebroventricular administration of captopril, were studied in normotensive Wistar rats. The blood-brain barrier permeability-surface area product (PS), determined by an integral-uptake method, was about 1 X 10(-5) cm3/g/s in all brain regions studied. This was three to four times lower than the simultaneously determined PS of Na+ and Cl-, both of which are known to have very low blood-brain barrier permeability. Cerebral blood flow, determined by the intra-arterial 133xenon injection method, was unaffected by intracerebroventricular administration of 100 micrograms captopril. Furthermore the lower limit of cerebral blood flow autoregulation during haemorrhagic hypotension was also unaffected, being in the mean arterial pressure range (50-69 mmHg) in both controls and captopril-treated rats. It was concluded that the blood-brain barrier permeability of captopril was negligible and that inhibition of the brain renin-angiotensin system has no effect on global cerebral blood flow. The cerebrovascular effects of intravenously administered captopril (a resetting to lower pressure of the limits and range of cerebral blood flow autoregulation) are probably exerted via converting enzyme on the luminal surface of cerebral vessels.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Ischaemic brain damage induced by rapid lowering of arterial pressure in hypertension.

Mean arterial pressure (MAP) and cerebral blood flow were monitored in six normotensive [MAP = 99 +/- 3 mmHg (s.e.m.)] and seven baboons with renovascular hypertension (MAP = 140 +/- 5 mmHg). Arterial pressure was decreased sufficiently rapidly and for a sufficient time, as determined by the electroencephalogram (EEG), to result in ischaemic brain damage. Using a combination of a bolus injection of trimetaphan, head-up tilt and acute withdrawal of blood, an isoelectric EEG was achieved at a higher MAP in the hypertensive (32 +/- 2 mmHg) than in the normotensive (19 +/- 1 mmHg: P less than 0.001) animals. Cerebral blood flow decreased to an equivalent degree in both groups. Ischaemic brain damage accentuated in the arterial boundary zones was seen in five normotensive and six hypertensive animals. This is further evidence that the resistance vessels in chronic hypertension may limit the degree of hypotension (therapeutic or accidental) that can be tolerated by the hypertensive patient.

Animals↗
PubMed1983

Differential effects of locus coeruleus lesions upon metabolic activity in CNS nuclei involved in cardiovascular regulation.

The alterations of local cerebral glucose utilization in 5 medullary and 6 supramedullary regions involved in cardiovascular regulation, which result from unilateral electrolytic lesions of the locus coeruleus, have been examined in conscious rats, using the quantitative autoradiographic [14C]2-deoxyglucose technique. Unilateral lesions of the locus coeruleus (72 h prior to study) did not result in any significant alteration in glucose utilization in any of medullary (e.g. nucleus of the tractus solitarius, dorsal motor nucleus of the vagus) or diencephalic (e.g. periventricular and paraventricular hypothalamic nuclei, lateral habenular nucleus) regions which were examined. However, the increased glucose utilization which occurred in some medullary nuclei (e.g. nucleus of the solitary tract, dorsal motor nucleus of the vagus) following administration of the alpha-receptor antagonist, phenoxybenzamine (30 mg/kg, i.v.), was significantly attenuated by lesions of the locus coeruleus, whereas the increased glucose utilization elicited in hypothalamic nuclei by the drug was unaffected by locus coeruleus lesions. In contrast, glucose utilization in the lateral habenular nucleus was elevated significantly following phenoxybenzamine only in animals bearing unilateral locus coeruleus lesion; the drug being without effect in this region in sham-lesioned rats. These differential consequences of locus coeruleus lesions upon glucose utilization in nuclei involved in cardiovascular regulation emphasize the complex nature of the influence of the locus coeruleus upon blood pressure control.

Animals↗
PubMed1983

Head injury in man and experimental animals: neuropathology.

All of the principal types of brain damage that occur in man as a result of a non-missile head injury, viz. cerebral contusions, intracranial haematoma, raised intracranial pressure, diffuse axonal injury, diffuse hypoxic damage, and diffuse swelling have been produced in subhuman primates subjected to inertial, i.e. non-impact, controlled angular acceleration of the head through 60 degrees in the sagittal, oblique and lateral planes.

Animals↗
PubMed1983

The effect of congenital and adult-acquired Toxoplasma infections on the motor performance of mice.

Motor performance was assessed in three groups of mice infected with Toxoplasma. One group was infected when adult. Two groups were infected congenitally: the first was born to dams infected during gestation and the second to dams which were chronically infected prior to mating. All mice were placed individually on a rotating cylinder and the number of falls from it noted over a two-minute period. Infected mice fell significantly more often than uninfected controls. The difference was independent of emotionality (as measured by defaecation) and general body health (as measured by body weight and a subjectively assessed health rating). There was no significant difference in motor performance between the two congenitally infected groups. However, the offspring of mice infected during pregnancy fell significantly more often than mice infected when adult. There were no significant correlations between motor performance and the actual number of Toxoplasma tissue cysts in the brains (or in separate defined sectors of the brains) of infected mice. We suggest that differences between infected and uninfected mice result from pathological changes caused by proliferating toxoplasms in the brains of infected mice. An immunopathological reaction due to the presence of the tissue cysts may also be involved. Other possible factors contributing to observed deficits in motor performance of infected mice are discussed. We suggest that such interference with the motor performance of Toxoplasma infected mice may render them more susceptible to predation by the domestic cat, the definitive host of Toxoplasma.

Animals↗
PubMed1983

The effect of congenital and adult-acquired Toxoplasma infections on activity and responsiveness to novel stimulation in mice.

Activity and responsiveness to novel stimulation were assessed in three groups of mice infected with Toxoplasma. One group was infected when adult; two groups were infected congenitally, one born to dams infected during gestation, the other to dams chronically infected prior to mating. Each mouse was tested in a box, the floor of which was marked off into 16 equal squares, and its activity was measured over ten minutes by counting the number of times the mouse entered each square. Infected mice were more active. In addition, infected mice showed a smaller relative preference for the more novel central area of the box, especially towards the end of the observation period. These differences were independent of emotionality (as measured by defaecation counts), general health (as measured by subjective health ratings and body weight) and the number of Toxoplasma tissue cysts in specified brain regions. We suggest that differences arise from pathological changes caused by proliferating toxoplasms in the brains of the infected mice; an immunopathological reaction due to the presence of tissue cysts in the brain may also be involved. Other possible factors contributing to observed deficits in behaviour are also discussed. We suggest that such deficits may render Toxoplasma-infected mice more susceptible to predation by the domestic cat, the definitive host of Toxoplasma.

Animals↗
PubMed1983

Effect of diazoxide-induced hypotension on cerebral blood flow in hypertensive rats.

The effect on cerebral blood flow of acute diazoxide-induced hypotension was studied in rats with renal and spontaneous hypertension. Diazoxide (5 mg/kg, i.v. bolus), caused arterial pressure to fall rapidly to that of normotensive rats, i.e. c. 75 mmHg. There was a concomitant fall in cerebral blood flow of about 35% (P less than 0.01) in renal hypertensive rats and 25% (P less than 0.05) in spontaneously hypertensive rats; the greater fall in flow in the former corresponded to a greater drop in pressure. Flow remained at these reduced levels during a 2 h observation period. Histological examination revealed small areas of ischaemic damage in the brains of five of the twelve animals. In control hypertensive rats not given diazoxide, cerebral blood flow and blood pressure were stable during a 2 1/2 h period and there was no evidence of ischaemic damage to the brains. The diazoxide-induced reduction in cerebral blood flow was interpreted as being secondary to a blood pressure fall to below the lower limit of cerebral blood flow autoregulation. No evidence was found of direct effects on the cerebral circulation such as seen with ganglionic blockers, alpha-blockers and cerebral vasodilators.

Animals↗
PubMed1983

Invited review. Nervous system antigens.

Some of the better characterized proteins (markers) of the nervous system are described. The availability of specific antibodies to these markers has allowed the localization and assay of the proteins in tissue and biological fluids. There is some evidence that autosensitization may occur. Clinical application of these markers includes the evaluation and prognostic significance after stroke and head injury. The diagnostic histopathological use of the markers in the investigation of various tumours is summarized.

Antigens↗