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Biomedical subjects

D J Boullin

Publications and source records attributed to D J Boullin.

At least 19 recordsLinked to original sources
PubMed1987

Platelets in the subarachnoid space. A cause of acute and delayed arterial spasm, intimal damage and cerebral infarction.

In nine baboons following intracisternal injection of a suspension of their own washed platelets, biphasic spasm was demonstrated by vertebral angiography. Constriction of the intra-arachnoid portion of the vertebral artery and the basilar artery was severe 10 minutes after the platelet injection, had begun to relax after one hour, but had returned on day 2 or 3. It persisted for about 8 days. The animals showed clinical evidence of neurological damage. At autopsy the vertebral and basilar arteries showed stripping of the endothelium, with adherent platelets, protein and other cells. There was blockage of some small branches. The brains showed ischaemic changes. The clinical phenomenon of spasm after subarachnoid haemorrhage was thus fairly closely modelled by the injection of platelets alone. There was some evidence that 5HT was probably not responsible for the delayed phase of spasm. Some suggestions are made about the mechanism.

Animals↗
PubMed1984

CSF smooth-muscle constrictor activity associated with cerebral vasospasm and mortality in SAH patients.

Cerebrospinal fluid (CSF) was collected preoperatively (by lumbar puncture) or perioperatively (by lumbar or ventricular drain) from 32 patients with subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms. Samples were also obtained from six control patients without evidence of subarachnoid blood. Smooth-muscle constrictor activity in the CSF was measured by bioassay using the isolated rat stomach fundus preparation. Concentrations of unidentified smooth-muscle constrictor substances were considerably greater in CSF from a group of seven patients with evidence of severe angiographic vasospasm and/or delayed ischemic deficits who died (73.8 +/- 39.7 nmol/liter prostaglandin E2 (PGE2) equivalents), as compared to 25 other SAH patients who survived (6.5 +/- 1.4 nmol/liter PGE2 equivalents), and six control patients (1.17 +/- 0.34 nmol/liter PGE2 equivalents). The data suggest that there is a relationship between smooth-muscle constrictor substances in the CSF after SAH and both the degree of angiographic vasospasm and the outcome. It is possible that this relationship might be exploited clinically.

Humans↗
PubMed1984

Simplified determination of serotonin in plasma by liquid chromatography with electrochemical detection.

This simplified determination of serotonin in human plasma involves "high-performance" liquid chromatography with electrochemical detection. Deproteinated samples of platelet-poor plasma are injected directly into the chromatograph without preliminary chromatographic purification. The limit of quantitative detection of serotonin in plasma is 5 nmol/L (equivalent to 250 fmol injected). Intra- and inter-assay CVs ranged from 5.6% to 7.7% and 3.5% to 14.9%, respectively, for concentrations of serotonin from 0.02 to 10.0 mumol/L. Results agreed well with those by spectrofluorometry, both for plasma standards (r = 0.985, range 100 nmol/L to 100 mumol/L) and for pathological samples obtained from four carcinoid syndrome patients (r = 0.964). The method is also applicable to the concurrent measurement of 5-hydroxytryptophan and 5-hydroxyindoleacetic acid.

5-Hydroxytryptophan↗
PubMed1983

Leukotriene D4 and the cerebral vasculature in vivo and in vitro.

The effects of leukotriene D4 (LTD4), a component of the slow reacting substance of anaphylaxis (SRS-A), and the putative SRS-A antagonist FPL 55712 were studied on cerebral arteries in vivo and in vitro. Intracarotid injection of LTD4 (1-15 nmols/kg) into the cerebral vasculature of the anaesthetised rat constricted internal and external carotid, facio-lingual and stapedial arteries for up to 40 minutes. LTD4 at 3 nmol/kg caused a slight fall in heart rate, and at 6 and 12 nmol/kg, an increase in diastolic (but not systolic) blood pressure was observed. In some experiments, constriction was followed by dilatation (possibly due to enhanced prostacyclin synthesis). FPL 55712 (0.3 to 30 nmols/kg) injected in the same manner caused both constriction and dilatation of rat cerebral arteries. In vitro experiments were performed on isolated human intracranial arteries (basilar, vertebral and Circle of Willis) obtained at autopsy, and on the isolated rat stomach fundus. LTD4 (2 x 10(-9) to 2 x 10(-7) M) caused sustained contractions of isolated human intracranial arteries. FPL 55712 (up to 4 x 10(-7) M) failed to antagonise the vasoconstrictor effects of LTD4, and higher concentrations (8 x 10(-6) to 8 x 10(-5) M) directly relaxed cerebral arteries. In contrast, FPL 55712 (2 x 10(-8) M) was a competitive antagonist of the contractile effects of LTD4 on the isolated rat fundus. This data suggests that the cerebral arterial leukotriene receptor differs from the peripheral smooth muscle receptor typified by the guinea-pig ileum and rat fundus preparations. Furthermore, leukotrienes may be involved in pathological vasoconstriction of various vascular beds after immunological reaction and trauma.

Animals↗
PubMed1983

The 5-hydroxytryptamine antagonist ketanserin inhibits the vasoconstrictor activity of per-operative CSF, from subarachnoid haemorrhage patients, on isolated tissues.

Peri-aneurysmal CSF was obtained at operation from 13 patients with subarachnoid haemorrhage from ruptured intracranial aneurysms. The 5-hydroxytryptamine antagonist ketanserin inhibited contractions of isolated human intracranial arteries, elicited by this CSF. The presence of 5-HT in CSF was confirmed by high performance liquid chromatography. The use of ketanserin in the therapy of postoperative cerebral vasospasm is discussed.

Adult↗
PubMed1983

The role of hemoglobin in the etiology of cerebral vasospasm. An in vivo study of baboons.

Oxyhemoglobin was injected intracisternally into three baboons, and methemoglobin into one baboon, in an attempt to mimic the prolonged cerebral arterial spasm sometimes seen after subarachnoid hemorrhage due to aneurysm rupture. Cerebral angiography was performed for up to 7 days after injection of hemoglobin, and the degree of vasospasm was estimated from the angiograms. Oxyhemoglobin caused slight arterial narrowing, which lasted for 3 days. Methemoglobin had no significant effects. Motor neurological deficits and histopathological signs, characteristic of prolonged cerebral vasospasm, were not observed. It was concluded that hemoglobin alone is not capable of causing the cerebral vasospasm syndrome in these experimental animals.

Animals↗
PubMed1981

Platelet shape change in patients with psychiatric disorders and treated with phenothiazines, thioxanthines, butyrophenones, benzodiazepines, tricyclic antidepressants and beta-adrenergic blocking agents.

Platelet shape change responses to 5-hydroxytryptamine were examined in 11 normal subjects and in 78 patients with psychiatric disorders receiving one or more of the following classes of drug: phenothiazine, thioxanthine, butyrophenone, tricyclic antidepressant, benzodiazepine or lithium. Approximately 37% of patients received a single drug, the remainder up to 4 other compounds in addition to the main drug. Platelet shape change induced by 5-hydroxytryptamine (0.25, 2.5 or 25 nmol/ml) was significantly inhibited in patients treated with phenothiazines, thioxanthines and butyrophenones (haloperidol). Tricyclic antidepressants, lithium and benzodiazepines had no effect on 5-hydroxytryptamine-induced shape change. In contrast, a combination of lithium plus chlorpromazine significantly enhanced platelet shape change. Potentiation of noradrenaline-induced aggregation was approximately 50% in normal subjects. This degree of potentiation was not altered in the drug-treated patients although there were quantitative reductions in magnitude of response. Platelet shape change in addition to platelet aggregation may be used as a pharmacological tool to investigate the aetiology of psychiatric disorders and, perhaps eventually, to monitor the clinical efficacy of drug therapy.

Adrenergic beta-Antagonists↗
PubMed1981

The calibre of cerebral arteries of the rat studied by carotid angiography: a model system for studying the aetiology of human cerebral arterial constriction after aneurysmal rupture.

Rupture of human cerebral arterial aneurysms is followed by prolonged cerebral arterial constriction; there is evidence that cerebrospinal fluid (CSF) from such patients contains vasoconstrictor substances which may cause the arterial constriction. The aim of this study was to develop a small animal model for investigating the effects of such CSF on the calibre of cerebral vessels in situ. Carotid angiography of the cerebral arteries of the rat visualizes the internal carotid, middle cerebral, anterior cerebral and stapedial arteries plus the vertebrobasilar system. Prostacyclin was injected during carotid catheterisation to prevent spontaneous and random occlusion of these cerebral arteries; in the presence of prostacyclin there was no arterial occlusion for up to 5 h. The resolution achieved by the angiographic technique, which magnified the cerebral circulations 2.9 times, was sufficient to measure the diameter of the internal carotid and stapedial arteries of the rat. Intracarotid infusion of 1.0 ml CSF collected from patients with ruptured cerebral arterial aneurysms caused a rapidly developing contraction of cerebral arteries lasting up to 5 h. Thus, we consider that the rat may also be used as a model for investigating the aetiology of human cerebral arterial constriction after aneurysmal rupture.

Animals↗
PubMed1981

Spinal trauma: pharmacological evidence for vasoconstrictor activity in cerebrospinal fluid.

Cerebrospinal fluid from six cases of acute spinal trauma collected 0--6 days after injury was examined for vasoconstrictor activity using both human isolated cerebral arteries and animal tissues. The cerebrospinal fluid of four out of six patients was vasoactive. The identities of the vasoconstrictor substances were not established, but experiments with pharmacological antagonists showed that arterial contractions were not due to serotonin, histamine, noradrenaline, acetylcholine or angiotensin II, substances which are known potent spastic agents on cerebral arteries. Our findings would explain by the mechanism of arterial spasm, principally in the anterior spinal artery, the neuropathological appearance of central haemorrhagic necrosis in spinal cord injury. The infarction of the core of the spinal cord could be caused by vasoconstrictor substances, reported here, in the cerebrospinal fluid after spinal injury. If the identities of the substances could be established, drug therapy to prevent or relieve the spasm would be possible.

Adolescent↗
PubMed1981

Vasoconstrictor activity in cerebrospinal fluid from patients subjected to early surgery for ruptured intracranial aneurysms.

Vasoconstrictor activity was examined in serial samples of cerebrospinal fluid (CSF) obtained from 10 patients undergoing aneurysm clipping within 48 hours after subarachnoid hemorrhage (SAH). There was no close relationship between vasoconstrictor activity in postoperative CSF samples and the patient's clinical condition or angiographic vasospasm. The identity of the vasoconstrictor substance(s) in CSF was not established, but serotonin, histamine, norepinephrine, epinephrine, acetylcholine, or angiotensin II were eliminated as prime vasoconstrictor agents inducing cerebral vasospasm. Differences in the temporal profile of the responses of isolated tissues to CSF from patients with early and late surgery suggested that differing substances were involved in the production of spasm. A correlation between CSF potassium concentrations and vasoactive substances was found, but potassium could not account for vasoconstrictor activity of CSF. A log:linear correlation between total vasoconstrictor activity and total CSF collected could not be explained. Also, because of possible differences in the identity of vasoactive substances in CSF in this study compared to earlier studies, clinical comparisons based on apparent differences in pharmacological potency of CSF were not warranted. Nevertheless, removal of subarachnoid blood by cisternal rinsing seemed to be a useful surgical adjunct.

Adult↗
PubMed1979

Responses of human and baboon arteries to prostaglandin endoperoxides and biologically generated and synthetic prostacyclin: their relevance to cerebral arterial spasm in man.

1 Isolated strips of human or baboon basilar, middle cerebral, vertebral or common carotid arteries were set up in an isolated organ bath or in a superfusion cascade system. 2 These arteries relaxed to prostacyclin but contracted to prostaglandin endoperoxide (PGH2). 3 Human and baboon isolated arteries also generated prostacyclin from exogenous endoperoxide (PGH2). 4 Human arteries generated prostacyclin 36 h post-mortem but not 40 h post-mortem. The biologically generated prostacyclin relaxed the basilar artery and overcame the contractile effects of PGH2. 5 Thromboxane A2-like activity generated during human platelet aggregation by arachidonic acid caused contractions of the human basilar artery. 6 Prostacyclin reversed contractions of human basilar arteries caused by an unidentified vasoconstrictor factor in cerebrospinal fluid obtained from patients with cerebral arterial vasospasm after subarachnoid haemorrhage following rupture of cerebral arterial aneurysms. 7. The above vasospasm may be due at least in part to disordered physiological control of the calibre of cerebral arteries caused by diminished synthesis of prostacyclin.

Animals↗
PubMed1979

Relationship between presence of vasoconstrictor activity in cerebrospinal fluid and time after subarachnoid haemorrhage from rupture of cerebral arterial aneurysms.

The relationship between clinical condition and vasoconstrictor factors in cerebrospinal fluid was studied in 19 patients for up to six weeks after subarachnoid haemorrhage. Vasoconstrictor activity was assayed biologically. Sixteen of 19 patients improved as vasoconstrictor activity declined; this pattern was not significantly influenced by surgery. Serial angiography was performed on three patients and a qualitative relationship was shown between arterial dilatation, clinical improvement, and reduced pharmacological activity.

Adult↗
PubMed1979

Responses of baboon cerebral and extracerebral arteries to prostacyclin and prostaglandin endoperoxide in vitro and in vivo.

The responses of baboon cerebral and extracerebral arteries to prostaglandin endoperoxide (PGH2) and prostacyclin (PGI2) were investigated on isolated arteries and in vivo by serial angiography. Both PGH2 and PGI2 could produce dose-dependent contraction or relaxation of isolated arteries. PGH2 induced relaxation was indicative of prostacyclin synthetase activity, the enzyme which converts PGH2 to PGI2. In isolated arteries tested one to four hours post mortem only the vertebral artery showed prostacyclin synthetase activity. Thus PGH2 induced contraction of cerebral arteries may be indicative of a physiological function. Vasomotor tone may in part be the result of a balance between PGH2 constriction and PGI2 dilatation. In vivo PGI2 infusion caused pronounced and prolonged dilatation of cerebral arteries, which lasted longer than the cardiovascular changes. As PGI2 is the most potent cerebral vasodilator drug tested, it may be of clinical use in the treatment of cerebral vasospasm.

Animals↗
PubMed1979

[Biochemical methodology for studying affective disorders].

Defects in brain neurotransmitter function are believed to be involved in the aetiology of mood disorders, and model systems are based on this concept. Abnormalities in synthesis, storage, release, reuptake or catabolism of monamines, GABA, glycine, taurine, peptides and purines may occur. There may also be an endogenous psychotogen--an aberrant metabolite of a transmitter. Models are divided into two groups. 1. Human. Brain, CSF, blood cells (platelets, erythrocytes), plasma and urine have been analysed for neurotransmitters or metabolites. Particular emphasis has been given to serotonin (5-HT) and the catecholamines, dopamine and noradrenaline. 2. Animal. Human mood disorders may be stimulated by drug-induced behavioural changes in animals (hyperactivity, stereotyped behaviour sedation). The above biochemical parameters relating to neuronal function can then be assessed. Brain neuronal pathways can be stimulated in animals with monoamine precursors and MAO inhibitor drugs. This drug-induced hyperactivity can be used to "evaluate" therapeutic techniques such as electroconvulsive therapy (ECT). Model analogues of mood disorder have limited use until human disease aetiology is known, currently the best use of models may be for demonstration and evaluation of particular similarities between human mood disorders and drug-induced alterations of animal behavioural patterns.

Animals↗