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Biomedical subjects

D I Graham

Publications and source records attributed to D I Graham.

At least 271 records · Page 15Linked to original sources
PubMed1983

Effect of chronic alcohol ingestion on the heart and blood pressure of spontaneously hypertensive rats.

The effect on the heart of a combination of high blood pressure and chronic alcohol ingestion was studied in spontaneously hypertensive rats (SHR) fed ethanol in their drinking water in concentrations of 0%, 5% and 20% for sixteen weeks. Normotensive Wistar rats were used as controls (NCR). In addition some SHR were given alcohol for a shorter period of eight weeks at the end of which time there were no significant differences in mean arterial blood pressure between the groups. After sixteen weeks of ethanol the mean arterial pressure had fallen in those SHR receiving 20% ethanol to 136 +/- 24 mmHg compared to control (180 +/- 27 mmHg; P less than 0.001). This was associated with a lower left ventricular (LV)dp/dt (control 4800 +/- 872 mmHg sec-1; 20% ethanol group = 3450 +/- 1588 mmHg sec-1; P less than 0.025) and a reduced LV weight (corrected for body weight) due to an apparent lack of development of LV hypertrophy between eight and sixteen weeks. Similarly LV volume (corrected for LV weight), did not change from eight weeks to sixteen weeks in those SHR receiving 20% ethanol in contrast to the 0% ethanol SHR group in whom LV volume fell as LV hypertrophy developed. 5% Ethanol had no significant effect on mean arterial pressure, LV peak dp/dt, LV weight or LV volume. In the NCR ethanol had little effect on mean arterial pressure but those receiving 20% ethanol had significantly smaller LV volumes without any increase in LV weight probably reflecting blood volume depletion. Ethanol did not produce any blood pressure elevation in the NCR. No rats (SHR or NCR) developed overt heart failure or a typical cardiomyopathy. However, this study has shown that a high intake of ethanol reduces the blood pressure of a hypertensive rat most likely by its direct toxic action on the myocardium. Thus with chronic alcohol ingestion hypertension can be masked but may still contribute significantly to the development of myocardial disease.

Alcoholism↗
PubMed1983

Correlation between angiographic vasospasm, hematoma, and ischemic brain damage following SAH.

The correlation between angiographic vasospasm, hematoma, and ischemic brain damage was studied in 29 patients who died as a result of subarachnoid hemorrhage following rupture of a saccular aneurysm. None of these patients was treated surgically. A comprehensive neuropathological examination was undertaken in each case. A significant relationship between the presence and degree of vasospasm and ischemic brain damage was found. Furthermore, even though intracerebral hematoma probably increased the risk of infarction associated with vasospasm, hematoma per se did not increase the incidence of ischemic brain damage.

Adolescent↗
PubMed1983

Cerebrovascular effects of the converting enzyme inhibitor captopril.

The effect of captopril on cerebral blood flow (CBF) and its autoregulation was studied in spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Wistar rats. CBF was measured by the intracarotid 133Xe injection method. In one study 1 and 10 mg/kg captopril respectively were given intravenously to SHR and WKY. This caused the blood pressure to fall transiently below the lower blood pressure limit of CBF autoregulation; nonetheless CBF remained normal during captopril induced hypotension. In a second study it was shown with an integral uptake method that captopril is a very poor penetrator of the blood-brain barrier. In a third study captopril was instilled intracerebroventricularly in Wistar rats without any effect on CBF or its autoregulation. Thus when given intravenously, but not intracerebroventricularly captopril caused cerebral vasodilatation during acute hypotension.

Animals↗
PubMed1982

Specific alterations in local cerebral glucose utilization following striatal lesions.

Regional cerebral glucose utilization was measured in conscious, lightly restrained rats, using the 2-deoxyglucose autoradiographic technique, 10 days after the unilateral injection of kainic acid into the striatum. The stereotactic infusion of kainic acid (2 mug in 2 mul of mock CSF) resulted in lesions localized to the caudate nucleus with no involvement of surrounding brain areas, such as septal nucleus and nucleus accumbens. Only mechanical damage around the needle tract was observed in CSF injected control animals. Local cerebral glucose use was most markedly affected ipsilateral to the infusion site in areas which normally receive input from the caudate nucleus. In globus pallidus and substantia nigra pars reticulata, increases in glucose use of 82% and 74%, respectively, were measured when compared with CSF injected controls. However, significant increases were also measured in contralateral pallidus and substantia nigra reticulata (16% and 20%, respectively). Of the brain structures examined, significant unilateral increases from control were observed in ipsilateral habenula (23%) and ventrolateral thalamus (13%), and contralateral substantia nigra pars compacta (14%) and sensory-motor cortex (15%). However, the side-to-side difference in response from control was not large. Symmetrical, bilateral increases in glucose use were found in the nucleus accumbens (15%), ventral tegmental area (24%), and red nucleus (17%). The only area in which the measured rate of glucose use was decreased was the ipsilateral caudate nucleus. However, these changes were invariably associated with histologically definable tissue damage. Caution must therefore be exercised in the interpretation of this result and that from other areas where damage was apparent. The increases of functional activity, as measured by glucose utilization within certain regions in the absence of cellular damage, provide an insight into the mechanisms by which overt motor behavior returns to normal a short time after the removal of striatal interneurons and efferent perikarya by the neurotoxic action of kainic acid. Of particular interest are the responses observed contralateral to the affected striato-nigral system in view of the proposed functional interaction between the two sides of the brain in the absence of direct neuronal pathways.

Animals↗
PubMed1982

Diffuse axonal injury due to nonmissile head injury in humans: an analysis of 45 cases.

Forty-five cases of diffuse axonal injury (DAI) brought about by nonmissile head injury in humans are analyzed and compared with 132 cases of fatal head injury without DAI. All cases were subjected to a comprehensive neuropathological study. In the patients with DAI a statistically significant lower incidence of lucid interval, fracture of the skull, cerebral contusions, intracranial hematoma, and evidence of high intracranial pressure were found, with a higher incidence of head injury due to road traffic accident. Brain swelling and hypoxic brain damage were not statistically different in the two groups. The features of DAI in humans are compared with the DAI that has been produced in subhuman primates by pure inertial loading brought about by angular acceleration of the head. The available evidence indicates that DAI in human beings occurs at the time of head injury and is not due to complicating factors such as hypoxia, brain swelling, or raised intracranial pressure.

Adolescent↗
PubMed1982

Diffuse axonal injury and traumatic coma in the primate.

Traumatic coma was produced in 45 monkeys by accelerating the head without impact in one of three directions. The duration of coma, degree of neurological impairment, and amount of diffuse axonal injury (DAI) in the brain were directly related to the amount of coronal head motion used. Coma of less than 15 minutes (concussion) occurred in 11 of 13 animals subjected to sagittal head motion, in 2 of 6 animals with oblique head motion, and in 2 of 26 animals with full lateral head motion. All 15 concussioned animals had good recovery, and none had DAI. Conversely, coma lasting more than 6 hours occurred in one of the sagittal or oblique injury groups but was present in 20 of the laterally injured animals, all of which were severely disabled afterward. All laterally injured animals had a degree of DAI similar to that found in severe human head injury. Coma lasting 16 minutes to 6 hours occurred in 2 of 13 of the sagittal group, 4 of 6 in the oblique group, and 4 of 26 in the lateral group, these animals had less neurological disability and less DAI than when coma lasted longer than 6 hours. These experimental findings duplicate the spectrum of traumatic coma seen in human beings and include axonal damage identical to that seen in sever head injury in humans. Since the amount of DAI was directly proportional to the severity of injury (duration of coma and quality of outcome), we conclude that axonal damage produced by coronal head acceleration is a major cause of prolonged traumatic coma and its sequelae.

Acceleration↗
PubMed1982

Cerebral blood flow in rats with renal and spontaneous hypertension: resetting of the lower limit of autoregulation.

The effect of chronic hypertension on cerebral blood flow (CBF) was studied in anaesthetised rats. CBF was measured with the intracarotid 133Xe injection method. Rats with spontaneous and renal hypertension were compared with normotensive controls. The lower limit of autoregulation was determined during controlled haemorrhage. In the normotensive rats, CBF remained constant until mean arterial pressure (MAP) had decreased to the range of 50-69 mm Hg. Thereafter, CBF decreased with each further decrease in MAP. In both types of hypertensive rats, CBF remained constant until MAP had decreased to the range of 70-89 mm Hg. Thus, a 20-mm Hg shift of the lower limit of CBF autoregulation was found in both spontaneous and renal hypertensive rats. A neuropathological study revealed ischaemic brains lesions in half of the hypertensive rats following hypotension, whereas only a single lesion was found in one of six normotensive rats. No ischaemic brain lesions were found in a control study in which CBF was shown to be stable over a 21/2-h period. In conclusion, hypertensive rats showed a shift of the lower limit of CBF autoregulation as well as an increased susceptibility to ischaemic brain damage during hypotension. These findings presumably reflect hypertensive structural changes in the cerebral circulation.

Animals↗
PubMed1982

Principal neuropathological and general necropsy findings in 24 renal transplant patients.

The principal neuropathological and general pathological findings in a group of 24 patients with renal transplants who died in a nine-year period at the Western Infirmary, Glasgow, are described. Opportunistic infections--bacterial, protozoal, and fungal--were the commonest causes of death. Other causes included cardiac and vascular lesions, upper gastrointestinal bleeding and neoplasia.

Adolescent↗
PubMed1982

Intra-arterial histamine increases blood-brain transport in rats.

The neurotransmitter histamine is located in multiple compartments in the brain and may influence cerebral vessels during some conditions. We made measurements of cerebrovascular transport of labeled sucrose, alpha-aminoisobutyric acid (AIB), and horseradish peroxidase during sustained infusion of histamine into the internal carotid artery of anesthetized rats. Histamine increased the rates of transport of sucrose and AIB up to 237% in several brain regions and in different areas of cerebral cortex. The effect was dose dependent, was reversible within 2 h, and was mediated primarily by histamine H2-receptors. An increase in cortical water content occurred, and electron microscopic examination revealed that perivascular astroglial processes were swollen. There was a twofold increase in the number of endothelial pits and vesicles in cortical capillaries perfused by histamine. We conclude that histamine can influence the function of the blood-brain barrier.

Animals↗
PubMed1982

Cerebrovascular permeability following MCA occlusion in the rat. The effect of halothane-induced hypotension.

A quantitative autoradiographic technique that utilizes carbon-14-aminoisobutyric acid (14C-AIB) as a tracer was used to study alterations in cerebral microvascular permeability in 15 rats. Five were "sham-operated" controls and 10 underwent microsurgical, unilateral occlusion of the proximal middle cerebral artery (MCA). Histological changes indicative of focal cerebral ischemia were observed in only the latter 10 animals. These changes were confined to tissue normally perfused by the occluded MCA. After MCA occlusion, five animals were also subjected to transient halothane-induced hypotension (mean arterial blood pressure 50 mm Hg) for 20 to 30 minutes. Only in these five animals were blood-to-brain transfer constants (ki) significantly increased (by approximately 100%) at 4 hours after MCA occlusion. The topographical distribution of this alteration in cerebral microvascular permeability corresponded closely with the histological changes. Neither proximal MCA occlusion nor halothane-induced hypotension alone was associated with any focal or diffuse increase in ki after 4 hours.

Aminoisobutyric Acids↗
PubMed1981

Acceleration induced head injury in the monkey.I. The model, its mechanical and physiological correlates.

A system has been developed which is capable of inducing brain injuries of graded severity from mild concussion to instantaneous death. A pneumatic shock tester subjects a monkey to a non-impact controlled single sagittal rotation which displaces the head 60 degrees in 10-20 msec. Results derived from 53 experiments show that a good correlation exists between acceleration delivered to the head, the resultant neurological status and the brain pathology. A simple experimental trauma severity (ETS) scale is offered based on changes in the heart rate, respiratory rate, corneal reflex and survivability. ETS grades 1 and 2 show heart rate or respiratory changes but no behavioral or pathological abnormality. ETS grades 3 and 4 have temporary corneal reflex abolition, behavioral unconsciousness, and post-traumatic behavioral abnormalities. Occasional subdural haematomas are seen. Larger forces cause death (ETS 5) from primary apnea or from large subdural haematomas. At the extreme range, instantaneous death (ETS 6) occurs because of pontomedullary lacerations. This model and the ETS scale offer the ability to study a broad spectrum of types of experimental head injury and underscore the importance of angular acceleration as a mechanism of head injury.

Acceleration↗
PubMed1981

Acceleration induced head injury in the monkey. II. Neuropathology.

A comprehensive neuropathological study has been undertaken in 53 adult subhuman primates subjected to a single sagittal plane angular acceleration impulse. The types of injury produced correlated well with the input force and were very similar to those seen in fatal nonmissile head injuries in man. There was a fracture of the skull in 14 animals. Subdural haematoma occurred in 33 animals, contusions in the frontal and temporal regions of the brain in 39, and discrete intracerebral haematoma in 4. Brain shift and tentorial herniation were also seen. There was evidence of hypoxic brain damage in 22 animals, and central chromatolysis in Betz cells and in the motor nuclei of the brain stem in 16.

Acceleration↗
PubMed1981

Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion.

A procedure for occluding the stem of the proximal middle cerebral artery of the rat is described. The operation is performed under anaesthesia through a small subtemporal craniectomy. After occlusion, 3 animals were perfused with carbon block and 8 with a FAM fixative (40% formaldehyde, glacial acetic acid, and methanol). The findings were compared with sham-operated animals. Carbon black studies demonstrated an area of impaired perfusion corresponding to the territory of the occluded artery in each animal. Neuropathological studies invariably showed that there was ischaemic brain damage in the cortex and basal ganglia. The frontal cortex was involved in every animal, as was the lateral part of the neostriatum; the sensorimotor and auditory cortex were involved in most animals, whereas the occipital cortex and medial striatum were involved only infrequently. The damage produced by ischaemia could be readily distinguished from the small local lesion seen at the surgical site in sham-operated animals. The ability to produce a consistent focal ischaemic lesion in the rodent brain provides a technical approach that is sufficiently reproducible to enable investigation of the pathophysiology of ischaemia using recently developed autoradiographic and neurochemical methods.

Animals↗
PubMed1981

Focal cerebral ischaemia in the rat: 2. Regional cerebral blood flow determined by [14C]iodoantipyrine autoradiography following middle cerebral artery occlusion.

Local cerebral blood flow has been measured by quantitative autoradiography, employing [14C]iodoantipyrine as tracer, in rats killed half an hour after occlusion of the middle cerebral artery. The results were compared with pattern of local cerebral blood flow (CBF) in sham-operated rats and with neuropathological findings. In every animal there was a profound reduction (to 13% of control levels)in blood flow in the neocortex previously by the occluded artery. The level of blood flow in the areas in which ischaemic brain damage occurred was 0.24 +/- 0.03 ml g-1 min-1 (mean +/- SEM). this level of CBF is considerably greater than that reported following a similar surgical procedure in cats and primates. Moderate reductions in blood flow were also seen outside the territory of the occluded artery and in parts of the opposite hemisphere. Absolute increases in blood flow (hyperaemia) were seen only in the substantia nigra and globus pallidus ipsilateral to the occlusion. It is of the middle cerebral artery are reflections of alterations in neuronal function and metabolic activity secondary to the ischaemic lesion.

Animals↗
PubMed1979

Effects of increasing arterial pressure on cerebral blood flow in the baboon: influence of the sympathetic nervous system.

The influence of stimulation of the cervical sympathetic chain on the response of cerebral blood flow to hypertension induced by the intravenous infusion of angiotensin was studied in anaesthetised baboons. Cerebral blood flow was measured by the intracarotid 133Xenon injection technique. Possible lesions of the blood-brain barrier were studied by injecting Evans blue towards the end of the experiment and ischaemic brain damage was assessed following perfusion fixation. In a control group of five baboons blood flow increased by 53 +/- 9% (mean +/- S.E.) from the base line values in the arterial pressure range 130-159 mm Hg. In four baboons subjected to unilateral sympathetic stimulation flow increased by 16 +/- 4% in the same pressure range. In three baboons subjected to bilateral sympathetic stimulation there were no significant increases in flow until the arterial pressure had increased above 159 mm Hg. Disruption of the blood-brain barrier in the parietooccipital regions was only seen in the control animals but not in the stimulated baboons. Ischaemic brain damage was not observed with the exception of one small lesion in a single stimulated baboon. These findings provide strong support for the observations of Bill and Linder (1976) that activation of the cervical sympathetic can modify the level at which breakthrough of cerebral blood flow occurs in association with systemic hypertension.

Angiotensin II↗
PubMed1979

Diffuse cerebral ischemia in the cat: III. Neuropathological sequelae of severe ischemia.

The neuropathological consequences of sever diffuse cerebral ischemia were investigated in an animal model in which postischemic alterations of regional brain blood flow and energy metabolism had been previously characterized. Pentobarbital-anesthetized cats received either 15 or 30 minutes of ischemia produced by basilar artery and bilateral carotid artery occlusions plus mild hypotension; this was followed by 60 to 90 minutes of normotensive recirculation. The brains were perfusion-fixed for light microscopy. Both insult durations resulted in unequivocal ischemic cell change affecting neurons of the cerebral neocortex, striatum, thalamus, and hippocampus and portions of the rostral brainstem. Animals with 30 minutes of prior ischemia differed from those with 15 minutes of ischemia in showing a more apparent regional accentuation of ischemic change in the parasagittal cortical gyri--the sites of previously documented focal postischemic heterogeneities of blood flow and metabolism. In other respects, however, the overall distribution and spectrum of severity of the ischemic alterations were similar for the two insult durations. These data support the view that significant permanent neuronal injury may result from a period of cerebral ischemia as brief as 15 minutes.

Animals↗
PubMed1979

Glial fibrillary acidic protein (GFAP): purification from human fibrillary astrocytoma, development and validation of a radioimmunoassay for GFAP-like immunoactivity.

The extraction and purification of glial fibrillary acidic protein (GFAP) from human fibrillary cerebellar astrocytoma is described. Using an immunoperoxidase method, antisera raised to the protein showed specific staining of astrocytes in normal spinal cord and in tumours of astrocytic origin. A double antibody radioimmunoassay for GFAP in tissue extract was developed, the detection limit of the assay being 360 pg. Extracts of tissues other than brain or spinal cord did not cross-react significantly in the assay, neither did purified preparations of myelin basic and S-100 proteins. Levels of GFAP in normal CNS tissue were higest in spinal cord (1370 microgram/g wet weight) but a level of 3050 microgram/g wet weight was detected in a fibrillary astrocytoma.

Astrocytes↗