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Biomedical subjects

D I Graham

Publications and source records attributed to D I Graham.

At least 199 records · Page 11Linked to original sources
PubMed1989

Propofol: effects on indices of cerebral ischemia.

The effects of propofol given before and during a period of profound hypotension that caused incomplete global cerebral ischaemia were investigated in anaesthetised cats. Cortical cerebral blood flow, extracellular fluid pH, potassium and calcium ion activities, and electroencephalogram were recorded. Neuropathological outcome was also assessed. Propofol-treated animals had higher cerebral blood flows than control animals after the period of hypotension (p <0.05); they also had better correction of extracellular fluid acidosis and hyperkalaemia (p <0.01) and a late improvement in calcium ion activity (p <0.05). Neuropathological outcome was not significantly different between the groups.

Journal Article↗
PubMed1989

Ocular blood flow in unilateral carotid stenosis and hypotension.

Ocular blood flow was measured in the juxtapapillary choroid, retrolaminar optic nerve and ciliary body mesoderm using 14C-labelled iodoantipyrine with quantitative autoradiography in seven anesthetized baboons in an experimental model of cerebral and ocular ischemia induced by hemorrhagic hypotension following unilateral common carotid stenosis, with external carotid ligation. The eyes of seven baboons with unilateral common carotid occlusion were also examined histologically for evidence of structural changes. This autoradiographic method allowed measurement of blood flow in different ocular structures and a significant change was noted in the optic nerve of stenosed animals, without structural damage.

Animals↗
PubMed1988

The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat.

Excessive activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor has been implicated in the sequence of neurochemical events that results in irreversible neuronal damage in cerebral ischemia. The effects of the NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) upon the amount of ischemic brain damage has been assessed quantitatively in the lightly anesthetized rat. Focal cerebral ischemia was produced by the permanent occlusion of one middle cerebral artery (MCA), and the animals were killed 3 hours after the arterial occlusion. MK-801 (0.5 mg/kg) was administered intravenously either 30 minutes prior to MCA occlusion or 30 minutes after the induction of ischemia. Pretreatment with MK-801 reduced the volume of ischemic damage both in the cerebral cortex (by 38% compared with untreated rats with MCA occlusion; p less than 0.01) and in the caudate nucleus (by 18% compared with controls; p less than 0.05). Treatment with MK-801, initiated 30 minutes after MCA occlusion, reduced the volume of ischemic damage in the cerebral cortex (by 52% compared with controls; p less than 0.01). The volume of ischemic damage in the caudate nucleus was minimally influenced by MK-801 treatment initiated after MCA occlusion. The antiischemic effects of MK-801 were readily demonstrable despite the hypotension that MK-801 induced in rats anesthetized with halothane (0.5%), nitrous oxide (70%), and oxygen (30%). The potency of MK-801 in reducing ischemic brain damage, even when administered after the induction of ischemia, highlights the potential use of NMDA receptor antagonists for the treatment of focal cerebral ischemia in humans.

Animals↗
PubMed1988

Response of cerebral microvasculature to brain injury.

There is increasing evidence that there is a direct response of the cerebral microvasculature to head injury. We have investigated using SEM and TEM the response of microvessels within the white matter of the baboon brain to lateral head acceleration. There is rapid endothelial disruption and swelling of perivascular astrocytes near the sites of petechial haemorrhage. The formation of microvilli in all vessels reaches a peak at 6 h and extends at least 5 mm from the site of haemorrhage. The astrocyte response suggests a partial recovery by 6 h. The endothelial response is most marked in arterioles and venules and is maintained for 6 days after injury. We suggest there is a biphasic cerebrovascular response to brain injury. First there is rapid astrocytic swelling possibly correlated with transient disruption of the blood-brain barrier. This is followed by morphological changes in the endothelium of all vessels which are most marked in arterioles and venules and extend considerable distances throughout the neuropile. This response is discussed in the light of disruption of the blood-brain barrier.

Animals↗
PubMed1988

Freeze-fracture studies of reactive myelinated nerve fibres after diffuse axonal injury.

We have studied the axonal and myelin sheath response in diffuse axonal injury after angular acceleration using the freeze-fracture and thin section techniques. It was found that the glial-axonal junction was intact until 1 h after injury. But upon loss of the nodal axolemma specialisations, after 3 to 4 h, the dimeric particles of the glial-axonal junction (GAJ) were lost and, by 6 h, the myelin lamellae became separated from the axonal remnant. There was a correlated loss of glial membrane specialisations of the GAJ during this separation. In the internodal region a suggestion of membrane damage occurred after 20 min but discrete myelin dislocations (particle-free areas) were not found until 1-h survival and were extensive by 6 h. Areas of loosely organised myelin occurred between intact axons at 7-28 days after injury. No evidence for growth cone formation was obtained.

Animals↗
PubMed1988

Quantitation of photochemically induced focal cerebral ischemia in the rat.

This study was carried out with a recently developed model of focal cerebral ischemia in the rat based on the photochemical induction of thrombotic stroke using the dye Rose Bengal. We examined the change in the volume of the lesion and brain water content, in separate groups of rats, at different times (1, 4, 24, 72, and 168 h) after the induction of the ischemic lesion. The volume of ischemic damage increased rapidly between 1 and 24 h after the ischemic insult and decreased between 24 and 168 h. The lesion at 168 h was significantly larger than that following 1 h of ischemia and similar to that obtained at 4 h, suggesting that the maximum extent of tissue damage (without the involvement of significant edema) was reached within the first 4 h in this model. The enlargement of the lesion after 4 h correlated closely with changes in brain water content.

Animals↗
PubMed1988

Focal cerebral ischaemia in the cat: treatment with the glutamate antagonist MK-801 after induction of ischaemia.

The effects of the glutamate N-methyl-D-aspartate receptor antagonist MK-801 in reducing ischaemic brain damage have been examined in anaesthetised cats, with drug treatment being initiated 2 h after the induction of cerebral ischaemia. Focal cerebral ischaemia was produced by permanent occlusion of one middle cerebral artery, and the animals were killed 6 h later. The amount of early irreversible ischaemic damage was assessed at 16 predetermined stereotactic planes. Treatment with MK-801 (5 mg/kg, i.v.) 2 h after middle cerebral artery occlusion reduced significantly the volume of ischaemic damage (from 1,625 +/- 384 mm3 of the cerebral hemisphere in vehicle-treated cats to 792 +/- 385 mm3 in MK-801-treated cats). The demonstration of reduced ischaemic brain damage with MK-801, when the agent is administered after the induction of ischaemia, extends the therapeutic potential of such agents in the treatment of focal cerebral ischaemia in humans.

Animals↗
PubMed1988

Protective effect of the glutamate antagonist, MK-801 in focal cerebral ischemia in the cat.

The effects of the glutamate N-methyl-D aspartate (NMDA) receptor antagonist, MK-801, upon ischemic brain damage has been examined in anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery and the animal were killed 6 h later. The amount of early ischemic damage was assessed in coronal sections at 16 predetermined stereotactic planes. Pretreatment with MK-801 (5 mg/kg, i.v.), 30 min before occlusion of the middle cerebral artery significantly reduced the volume of ischemic damage (from 32.7 +/- 4.0% of the cerebral hemisphere in vehicle-treated cats to 16.2 +/- 4.5% in MK-801-treated cats). NMDA receptor antagonists that penetrate the blood-brain barrier, such as MK-801, merit further study as protective agents against ischemic brain damage.

Animals↗
PubMed1988

Experimental intracerebral mass: description of model, intracranial pressure changes and neuropathology.

In a rodent model designed to replicate the mass effects of spontaneous intracerebral hemorrhage, we have found that there is little change in intracranial pressure (ICP) with microballoons (25 microliters and 50 microliters in volume) equivalent in size to those lesions which occur with this disorder in man. With larger volumes (100 microliters) there is an increase in ICP which is associated with systemic effects on cerebral perfusion pressure (CPP). Neuropathological evidence of ischemic brain damage was found surrounding the mass in all animals, but this was independent of whether the mass was removed or not. These studies suggest that with a mass that corresponds to the size seen most commonly with spontaneous intracerebral hemorrhage in man, focal ischemic brain damage is produced without reduction in global CPP.

Animals↗
PubMed1988

Brain damage in fatal non-missile head injury without high intracranial pressure.

As part of a comprehensive study of brain damage in 635 fatal non-missile head injuries, the type and prevalence of brain damage occurring in the absence of high intracranial pressure were analysed. Of 71 such cases, 53 sustained their injury as a result of a road traffic accident; only 25 experienced a lucid interval. Thirty eight had a fractured skull, a mean total contusion index of 12.9 and diffuse axonal injury in 29: severe to moderate ischaemic damage was present in the cerebral cortex in 25, brain swelling in 13, and acute bacterial meningitis in nine. The prevalence and range of brain damage that may occur in the absence of high intracranial pressure are important to forensic pathologists in the medicolegal interpretation of cases of fatal head injury.

Adolescent↗
PubMed1988

Effects of hypotension induced with sodium nitroprusside on the cerebral circulation before, and one week after, the subarachnoid injection of blood.

Cerebral blood flow (CBF) and mean arterial pressure (MAP) were monitored in six normal baboons and six further animals in which an artificial subarachnoid haemorrhage (SAH) had been induced one week previously. MAP was reduced by the infusion of sodium nitroprusside. In the normal animals with administration of sodium nitroprusside, CBF increased initially but started to decrease as MAP was reduced below 65 mm Hg and fell below its baseline value when MAP was less than 50 mm Hg. In the SAH group, there was no initial hyperaemic response and CBF fell below baseline values when MAP was reduced below 50 mm Hg. When, during the infusion of the sodium nitroprusside, MAP was returned to normal using angiotensin, CBF increased above its baseline value. These results suggest that the cerebrovascular effects of sodium nitroprusside are the net result of competition between direct cerebral vasodilatation, falling arterial blood pressure and the degree of impairment of the "autoregulatory" mechanism. Evidence of ischaemic brain damage was found in the arterial boundary zones of both groups of animals.

Animals↗
PubMed1988

Experimental intracerebral haemorrhage: the effect of nimodipine pretreatment.

The effect of pretreatment with the calcium antagonist nimodipine on the pathophysiological events which follow an intracerebral haemorrhage in rats was compared with a similar control group. Cerebral blood flow was higher and the amount of pathologically determined ischaemic damage measured by light microscopy was less in the nimodipine pretreated group. Bloodbrain barrier permeability was increased in the nimodipine group, but there was no evidence of cerebral oedema. Nimodipine appeared to have no effect on the intracranial pressure.

Animals↗
PubMed1988

Experimental intracerebral hemorrhage: progression of hemodynamic changes after production of a spontaneous mass lesion.

The aim of the study was to determine whether the extent of ischemia produced by an experimental space-occupying lesion changed between 5 minutes and 4 hours after the production of a lesion. In two groups of rats, a 50-microliter balloon was inflated in the right caudate nucleus. Cerebral blood flow (CBF) was determined by 14C-iodoantipyrine quantitative autoradiography, in Group 1 (n = 6) 5 minutes after inflation and in Group 2 (n = 6) 4 hours later. After 5 minutes of inflation, the mean blood flow in the caudate nucleus was reduced to 65% of the contralateral value and 11.5% of the ipsilateral caudate nucleus had a blood flow of below 25 ml/100 g/minute. After 4 hours of inflation, there was a greater fall in the mean CBF of the ipsilateral caudate nucleus to 30% of the contralateral value, and 38.9% of the ipsilateral caudate nucleus had a CBF of less than 25 ml/100 g/minute. The differences between the two groups were significant (mean CBF, P less than 0.01; CBF less than 25 ml/100 g/minute, P less than 0.02). The results show that the initial ischemic lesion produced by a spontaneous intracerebral space-occupying lesion does not remain static, but progresses with time and is significantly greater after 4 hours than after 5 minutes. Interventions that reduce the progression of ischemia may be beneficial in reducing the ultimate amount of ischemic brain damage.

Animals↗
PubMed1987

Vasomotor effects of atrial natriuretic peptides on feline pial arterioles.

Vasomotor responses to atrial natriuretic peptide (ANP), atriopeptin I and atriopeptin II were examined on individual pial vessels on the cortical surface of chloralose-anaesthetized cats. The peptides were administered by subarachnoid perivascular microapplication in an open skull preparation. Changes in vessel calibre were quantified and compared to those of the vehicle, artificial cerebrospinal fluid, which was without significant vasomotor effect. All 3 atrial peptides significantly increased pial arteriolar calibre. ANP, the most potent, gave rise to a maximum increase in arterial calibre of 33 +/- 4% (mean +/- S.E.M., n = 7, P less than 0.05) at 10(-6) M. The concentration of ANP effecting half the maximum response was approximately 7 nmol. Atriopeptin I and II were equipotent with a maximum increase in calibre at 10(-6) M of 21 +/- 4% (n = 10) and 23 +/- 2% (n =6), respectively. The concentration of these peptides effecting half the maximum response was, similar to ANP, in the nanomolar range. Samples of pial arterioles along with middle cerebral and basilar arteries were processed for immunohistochemistry using a polyclonal antibody raised against human ANP. No specific ANP-immunoreactivity was found associated with these vessels. However, dense granular ANP-immunoreactive deposits were clearly demonstrated in sections of feline atria. We conclude that all 3 peptides studied are vasoactive in the cerebral circulation, ANP being the most potent. Since there is no evidence for perivascular ANP nerves around these vessels, the physiological significance of these findings must await identification of the source of ANP.

Animals↗