Cerebral Arterial Spasm Research Articles

Prostacyclin and cerebral vessel relaxation.

The authors have studied the ability of prostacyclin to reverse contractions of human basilar arteries in vitro that were induced by a wide range of substances implicated in the etiology of cerebral arterial spasm. Prostacyclin (10(-10) to 10(-6)M) caused a dose-related reversal of contractions induced by 5-hydroxytryptamine, noradrenaline, angiotensin II, prostaglandin (PG)F2 alpha, and U-46619 (a thromboxane-A2 mimetic). These agents were tested at concentrations or volumes that produced almost maximum or maximum responses and those that produced approximately 50% of the maximum response. Contractions induced by maximum concentrations of angiotensin II and U-46619 were least affected by prostacyclin. In addition, contractions induced by thromboxane-A2 generated from guinea-pig lung were reversed in a dose-dependent fashion by prostacyclin. This ability of prostacyclin to physiologically antagonize contractions of the human basilar artery in vitro induced by high concentrations of various spasmogenic agents suggests that such a potent vasodilator agent or more stable analogue may be of value in the treatment of such disorders as cerebral arterial spasm following subarachnoid hemorrhage.

CSF serotonin concentrations and cerebral arterial spasm in patients with ruptured intracranial aneurysm.

In 26 patients with recent rupture of an intracranial saccular aneurysm the CSF concentrations of serotonin (5-HT) were measured repeatedly by a radioimmunoassay. The 5-HT level in ventricular CSF collected between the 2nd and 15th day after SAH ranged between less than 2 and 5 nmol/l. These did not differ from the levels found in the ventricular CSF (less than 2-3 nmol/l) and lumbar CSF (less than 2-3 nmol/l) of control patients. 5-HT concentrations did not correlate with the severity of angiographical vasospasm, nor with CSF pressure or clinical grade. In two patients with severe postoperative vasospasm, however, cisternal CSF collected during operation and contaminated by fresh blood showed 5-HT concentrations exceeding 25 nmol/l. Thus, although these results do not support the conception that 5-HT plays a major role in sustaining delayed vasospasm, they suggest that 5-HT liberated from platelets may be operative in the initiation of cerebral arterial spasm.

Effect of fibrin-fibrinogen degradation products on human basilar artery preparations

Experiments were performed to determine the effects of fibrin-fibrinogen degradation products on the human basilar artery in vivo. Citrated plasma and streptokinase were incubated at 37 degrees C to produce a preparation of fibrinogen degradation products. Aliquots of the incubate were obtained at 90 minutes, 48 hours, and 1 and 2 weeks after preparation, and were separated into fractions of different molecular weight (MWt), using an ultrafiltration technique. Each fraction was tested at each of the above times for contractile activity and possible interaction with a threshold concentration of 5-hydroxytryptamine (5-HT) on the human basilar artery. Contractile activity was initially confined to the 90-minute aliquot fraction MWt greater than 100,000, but as the incubation proceeded, such activity was also seen in the lower MWt fraction less than 100,000 greater than 10,000 at all time intervals. This activity was never seen in the fraction MWt less than 10,000 at any time. Enhancement of the 5-HT response was initially confined to the higher molecular weight fractions, but after 48-hour incubation all fractions showed this activity. It is suggested that products of fibrin-fibrinogen degradation may be involved directly or indirectly in influencing the pathophysiological mechanism(s) responsible for cerebral arterial spasm following subarachnoid hemorrhage.

Intracranial pressure changes following aneurysm rupture. Part 1: clinical and angiographic correlations.

Intraventricular pressure (IVP) was measured continuously by the method of Lundberg for an average period of 8 days in 52 patients with recent rupture of an intracranial saccular aneurysm. The patients were graded as follows according to the system of Hunt and Hess: 13 patients were Grades I-II, 19 patients Grades II-III, and 20 patients Grades III-V. The degree of cerebral arterial spasm was measured on angiograms taken on admission and approximately 7 days later. Drainage of ventricular cerebrospinal fluid was performed intermittently when IVP exceeded 25 mm Hg. The results showed a close correlation between changes in clinical grade and in mean IVP. Drainage improved the condition in uncomplicated cases, but was less effective or ineffective when severe vasospasm or rebleeding occurred. Lowering the IVP by drainage did not appear to increase the risk of rebleeding. In contrast to patients with no or slight spasm, patients with severe spasm had a permanently elevated IVP, even before spasm was demonstrable angiographically. A mean IVP exceeding 25 mm Hg for the whole period of monitoring was associated with a poor prognosis. Finally, indications for continuous monitoring of IVP and ventricular drainage in aneurysm patients are suggested.

Intracranial pressure changes following aneurysm rupture. Part 2: associated cerebrospinal fluid lactacidosis.

Lactate concentrations and pH were measured serially in the cerebrospinal fluid (CSF) of 52 patients with ruptured intracranial aneurysms. Measurements were made during continuous monitoring of the intraventricular pressure (IVP) in the first 12 days after the initial subarachnoid hemorrhage. A total of 226 samples of CSF were analyzed. The clinical condition of the patients was graded according to the Hunt and Hess system. The degree of cerebral arterial spasm was measured on angiograms taken on admission and again approximately 7 days later. Results showed that the lactate concentrations in hemorrhagic and xanthochromic CSF were significantly higher than in clear CSF, indicating lactate production from shed blood cells. However, regardless of the degree of blood admixture to CSF, lactate increased with deteriorating clinical condition. Patients with a moderately increased IVP (20 to 40 mm Hg) had lactate levels of about 3 mmol/liter. A rising IVP or the development of severe spasm was accompanied by a persistent elevation or an increase in lactate. These results suggest that increased CSF concentrations of lactate reflected an increased production of lactate by partially ischemic cerebral tissue. A CSF lactate value above 3.5 mmol/liter was associated with a poor prognosis.

Reversal of experimental delayed cerebral vasospasm by angiotensin-converting enzyme inhibition.

Delayed cerebral vasospasm is an important determinant of the clinical outcome after subarachnoid hemorrhage, but its prevention and treatment has met with limited success. Since cerebral arteries were found to be sensitive to the vasoconstrictor effect of angiotensin II, the possibility of angiotensin's contribution to this vasospasm was investigated. Delayed cerebral arterial spasm was documented angiographically 72 hours after introduction of blood in the subarachnoid space of dogs. Following injection of the angiotensin-converting enzyme inhibitor, teprotide, repeat cineangiograms at 30, 60, and 90 minutes demonstrated partial or total release of spasm of the basilar artery and its branches. It is concluded that angiotensin II participates in the delayed cerebral vasospasm after hemorrhage, and that angiotensin inhibition may release the spasm and prevent cerebral ischemia.

Book Reviews

Book reviewed in this article: The Borderland of Epilepsy: A Reappraisal, M. Dam and J. G. Klee. The Endocrine Functions of the Brain (Comprehensive Endocrinology), Marcella Motta, (Ed.). The Aging Brain—Neurological and Mental Disturbances, G. Barbagallo‐Sangiorgi and A. N. Exton‐Smith (Eds.). Brain Tumours, D. G. T. Thomas and D. I. Graham, (Eds.). Cerebral Arterial Spasm: Proceedings of the Second International Workshop, Robert W. Wilkins (Ed.). Diagnosis and Nonsurgical Management of Chronic Pain, Nelson Hendler. Neurosurgical Anaesthesia and Intensive Care, T. V. Campkin and J. M. Turner. Basic Neuroscience, A. Afifi and R. Bergman. Operative Surgery: Neurosurgery, Lindsay Symon {Ed.)

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.

脳動脈攣縮の電子顕微鏡的研究

Despite of recent progress in neurosurgical techniques and managements, cerebral arterial spasm has been a difficult problem, which has great influence on prognosis for life as well as for function of patients with the ruptured aneurysm. Mechanisms of vasospasm after subarachnoid hemorrhage (SAH) have been intensively studied and elucidated to a certain extent in experimental models, however, once cerebral vasospasm has occurred in patients after subarachnoid hemorrhage, restoration of vascular caliber is extremely difficult. Moreover, it has been recently found that prolonged constriction of the vascular lumen in so-called vasospasm was partly due to organic changes of the arterial wall, such as myonecrosis and intimal thickenings. Since only a part of patients with prolonged vasospasm develops ischemic symptoms of the brain, intimal changes such as endothelial degeneration and desquamation with possible mural thrombosis might play an additional part to narrowness of the vascular lumen for manifestation of cerebral ischemia.From this point of view, the author studied the luminal surface of cerebral arteries of experimental vasospasm as well as human autopsy materials using a scanning electron microscope.1) Experimental studies:Prolonged spasm was induced in dogs by introducing fresh blood into the cisterna magna or by puncturing the intracranial internal carotid artery with a fine needle.On the luminal surface of the arteries four days after SAH, there were segmental longitudinal folds covered with undisrupted flat endothelial lining. The segmental presence of longitudinal folds in the specimen perfusion-fixed under pressure was interpreted that constriction of the arterial wall in vasospasm was not equally intense throughout the whole spastic portion, although narrowing of the arteries appeared diffuse on the angiomas, and that segments in severer spasm were not completely extended out at the time of fixation under pressure. The folds of the luminal surface were no more present in the specimens 10 days after SAH.Apparent degeneration and/or desquamation of the endothelial cells in the spastic segments were not recognized.2) Studies with h uman materials:Four fatal cases of severe subarach noid hemorrhage were studied. The arterial segments at the base of the brain were dissected at autopsy and examined on SEM.There were patches of area which was covered with fibrin network in three cases. In the remaining case the mural thrombus with fibrin and red blood cells were noted in a segment prepared for a light microscope. There was no endothelial lining beneath or around a fibrin net on the luminal surfaces. As a control study, proximal middle cerebral arteries were obtained at either medico-legal or pathological autopsy from 17cases died from other than intracranial diseases.There was frequent patchy desquamati on of the endothelial lining, showing flat and smooth surface, however, fibrin nets as well as fibrous structures alike were never encountered in a control study.It was assumed that in a severe prolonged spasm the endothelial cells underwent degeneration by prolonged compression, and that subsequent mural deposit of fibrin net could take place if increased coagulability of some kind and/or stasis of blood stream favoured it.3) Expe rimental studies could not supply any evidence supporting the assumption derived from findings obtained in human materials. The failure was undoubtedly due to great difficulty to reproduce prolonged spasm in dogs so severe as seen in clinical cases manifesting ischemic symptoms.It would be important for further experiments to establish experimental models, in which long-lasting severe spasm could be induced and yet no threatening to life of animals would exist.

Cerebral Arterial Spasm

In vivo experiments in dogs demonstrated angiographically that the subarachnoid injection of blood produced cerebral arterial apasm both immediately after the injection of blood and 2 days later. The sublingual adminstration of nifedipine reversed both the acute and the delayed cerebral arterial spasm. In addition, sublingual administration of nifedipine 20 minutes before the subarachnoid injection of blood prevented the acute spasm.

Pathological study of late arterial spasm (author's transl)

It is well known that cerebral vasospasm following ruptured cerebral aneurysm affects the prognosis very seriously after direct surgery. However, the pathogenesis of cerebral vasospasm remains obscure. Furthermore, the precise brain damage following it has not been made clear histopathologically. The histopathological postmortem studies of intracranial arteries with angiographycally demonstrated arterial narrowing have been carried out in 44 cases. The cerebral arterial wall corresponding to the angiographic vasospasm showed various structural changes, which could be divided into five groups according to histological findings. In Group 1, the intraluminal size of arterial wall was reduced even though the medial thickening, marked corrugation of the internal elastic lamina and intimal edema were demonstrated. In Group 2, necrosis of smooth muscle cells in the tunica media, partial break of internal elastic lamina and the profuse deposition of acid mucopolysaccharides were seen. In Group 3, marked intimal thickening and the medial atrophy were seen. In Group 4, dilatation of luminal size with improvement of the intimal thickening and the remarkable medial atrophy were noted. In Group 5, regeneration of smooth muscle cell in the tunica media was observed. These histological findings suggest the time course of cerebral arterial spasm from onset to remission.

An investigation with serial angiography into the evolution of cerebral arterial spasm following aneurysm surgery.

Serial postoperative angiograms were performed in 28 patients with intracranial aneurysms, 26 of whom had presented with a subarachnoid hemorrhage. The clinical state and intracranial pressure (ICP) were also measured. Angiograms were performed in the ward using a cannula, which was passed into the proximal external carotid artery via the superficial temporal artery. Measurements of the vessel diameters were made, with the preoperative angiogram as a baseline. Patients could be placed into one of five groups depending on the presence or absence of significant arterial spasm, the clinical state of the patient, and the normality or otherwise of the ICP. No patient's condition deteriorated without an elevated ICP and/or significant arterial spasm. The study shows that this spasm is usually associated with a poor clinical state if it reaches a maximum 8 to 12 hours after the operation, although the clinical deterioration is not apparent for a further 6 to 12 hours. Knowledge of the natural history of postoperative arterial spasm may allow earlier treatment of the spasm, which may be more successful than delaying treatment until clinical deterioration has occurred. The worth of the varied drugs proposed for the treatment of spasm may be assessed using this type of protocol.

MIGRAINE: A VASOMOTOR INSTABILITY OF THE MENINGEAL CIRCULATION

The current view that the migraine aura arises from spasm of the major cerebral arteries and the ensuing headache from extracranial arterial vasodilatation is examined and refuted. It is proposed that the headache is due to stimulation of nociceptive nerve-endings in the walls of meningeal vessels (arterioles, venules, and particularly the dural venous sinuses); and that the aura arises from calibre changes in meningeal vessels that penetrate the outer cortex, resulting in localised inhibition or excitation. It is suggested that there are two types of migraine patients— vasodilators and vasoconstrictors.

Human behavioural arousal induced by dopamine.

British Journal of Clinical PharmacologyVolume 6, Issue 4 p. 369-370 Free Access Human behavioural arousal induced by dopamine. DJ Boullin, DJ BoullinSearch for more papers by this authorCB Adams, CB AdamsSearch for more papers by this authorGH Du Boulay, GH Du BoulaySearch for more papers by this author DJ Boullin, DJ BoullinSearch for more papers by this authorCB Adams, CB AdamsSearch for more papers by this authorGH Du Boulay, GH Du BoulaySearch for more papers by this author First published: October 1978 https://doi.org/10.1111/j.1365-2125.1978.tb00866.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References ADAMS, C.B.T., LOACH, A.B. & O'LAOIRE, S.A. (1976). Intracranial aneurysms: analysis of results of micronerusurgery Br. med. J., 2, 607– 609. ALLCOCK, J.M. & DRAKE, C.G. (1965). Ruptured intracranial aneurysms The role of arterial spasm. J. Neurosurg., 22, 21– 29. BLASCHKO, H. & CHRUSCHIEL, T.L. (1960). The decarboxylation of amino acids related to tyrosine and their awakening action in reserpine-treated mice. J. Physiol., 151, 272– 283. BOULLIN, D.J., ADAMS, C.B.T., MOHAN, J., GREEN, A.R., HUNT, T.M., DU BOULAY, G.H. & ROGERS, A.T. (1977). Effects of intracranial dopamine perfusion: behavioural arousal and reversal of cerebral arterial spasm following surgery for clipping of ruptured cerebral aneurysms. Proc. roy. Soc. Med., 70, Suppl. 2, 55– 70. VON ESSEN, C. (1972). Effects of dopamine, noradrenaline and 5-hydroxytryptamine of the cerebral blood flow in the dog. J. Pharm. Pharmac., 24, 668. VON ESSEN, C. (1974). Effects of dopamine on the cerebral blood flow in the dog. Acta Neurol. Scand., 50, 39– 52. GREEN, A.R. & KELLY, P.H. (1976). Evidence concerning the involvement of 5-hydroxytryptamine in the locomotor activity produced by amphetamine or tranylcypromine plus L-dopa. Br. J. Pharmac., 57, 141– 147. MACPHERSON, P. & GRAHAM, D.I. (1978). Correlation between angiographic findings and the ischaemia of head injury. J. Neurol. Neurosurg. Psychiat., 41, 122– 127. Volume6, Issue4October 1978Pages 369-370 ReferencesRelatedInformation

Aetiology of cerebral arterial spasm following subarachnoid haemorrhage: evidence against a major involvement of 5‐hydroxy‐ tryptamine in the production of acute spasm.

Abstract 1 Acute cerebral arterial spasm was produced in baboons by intracisternal injection of blood or 5-hydroxytryptamine (5-HT). Blood induced spasm was not antagonized by the potent 5-HT antagonist BW501C67, but 5-HT induced cerebral arterial spasm was largely antagonized. 2 Blood platelets from baboons were isolated and aggregated in vitro with adenosine diphosphate (ADP) and 5-HT. 5-HT induced platelet aggregation was abolished by BW501C67 in vitro. It was also abolished after intracisternal administration of the drug. Thus it is concluded that BW501C67 antagonized 5-HT induced cerebral arterial spasm. 3 BW501C67 also failed to antagonize contractions produced by human cerebrospinal fluid, serum and platelet extracts on the isolated human basilar artery, the isolated rat fundus and aorta. 4 These results suggest that the role of 5-HT in the aetiology of human cerebral spasm may be minimal.

Intracranial pressure in patients with diffuse cerebral arterial spasm following ruptured intracranial aneurysms.

Intracranial pressure (ICP) was recorded continuously in 12 pre-operative patients with angiographic evidence of diffuse cerebral arterial spasm due to a ruptured intracranial aneurysm. Recordings were made for 1 to 7 days, starting within 13 days after the haemorrhage. 1. An increased ICP was observed in the first week after subarachnoid haemorrhage (SAH) in 4 of the patients without any signs of angiographic arterial spasm. 2. This initial increase was regularly followed by a depression of ICP in between 7--12 days after SAH. In 11 out of 12 patients such a depression was concomitant with the beginning of arterial spasm. During the period of depressed ICP pattern, 6 patients showed little or no neurological deterioration, whereas 5 patients showed impaired consciousness or neurological deficits. 3. A secondary rise of ICP thereafter always followed due to ischaemic brain swelling or infarction, and was usually associated with a serious neurological deterioration. 4. Continuous ventricular drainage was performed to control the secondary increased ICP in 7 patients who survived, 4 of them with good clinical improvement and 3 with severe neurological deficits. 5. In the stage of depressed ICP, the administration of isoproterenol and steroids is recommended in order to try to alleviate the secondary rise of ICP.

Cerebral arterial spasm: A discussion of present and future research.

The author presents a discussion of research on cerebral arterial spasm. Arterial smooth muscle contraction, receptor and relaxation mechanisms are presented in the context of what is known about cerebral arterial spasm and the biochemistry of vascular smooth muscle. Several new experimental approaches are suggested and a theoretical biochemical basis for the idea that damage to the artery alone could cause cerebral arterial spasm is postulated. Methods of determining cerebral arterial spasm and the need for a quantitative, in vivo method are discussed and the question of an irreversible stage of cerebral arterial spasm is considered. Finally, the problems associated with the delivery of a potentially successful treatment to the cerebral arterial smooth muscle cells are examined.

Effects of (+) and (-)-propranolol on the responses of the human isolated basilar artery to cerebrospinal fluid obtained from patients with subarachnoid haemorrhage and cerebral arterial spasm.

1. The human isolated basilar artery has been used as a model to investigate the aetiology of cerebral arterial spasm associated with rupture of intracranial aneurysms. 2. The isolated artery is contracted by 5-hydroxytryptamine, noradrenaline, six prostaglandins and cerebrospinal fluid from patients with ruptured aneurysms and cerebral arterial spasm. 3. These contractions are reversed by (+/-)--, (+)-- and (--)-propranolol in concentrations known to produce local anaesthetic effects on isolated frog sciatic nerve; the (+) isomer was 2.5 to 10 times more potent (-)-propranolol in antagonising all contractions. 4. As the two isomers are known to have similar local anaesthetic potency but (-)-propranolol has greater beta-adrenoreceptor blocking effects we conclude that the antagonistic effects described do not involve beta-adrenoreceptor blockade. 5. The data indicate that propranolol may be of clinical use in reversing cerebral arterial spasm.

Effects of Intracranial Dopamine Perfusion: Behavioural Arousal and Reversal of Cerebral Arterial Spasm following Surgery for Clipping of Ruptured Cerebral Aneurysms

Effects of Intracranial Dopamine Perfusion: Behavioural Arousal and Reversal of Cerebral Arterial Spasm following Surgery for Clipping of Ruptured Cerebral Aneurysms

実験的脳血管攣縮

Spasm of the major cerebral arteries occurs in more than 35 per cent of patients with subarachnoid hemorrhage due to the ruptured cerebral aneurysms, and the presence of severe spasm is known to affect greatly the prognosis of the patients. Despite extensive clinical and experimental investigations, no satisfactory treatment has been established up to the present.Experimental studies were performed to find out effective managements for cerebral arterial spasm. Cerebral vasospasm was produced experimentally by injection of autogenous fresh arterial blood into the cisterna magna of adult dogs and the effects of papaverine hydrochloride which was applied in various ways and concentrations, were evaluated.1. Biphasic cerebral vasospasm could be produced by injection of autogenous fresh arterial blood into the cisterna magna without vascular injuries and this model of experimental vasospasms was thought to be adequate for the present study.2. Papaverine hydrochloride was a potent vasodilating drug and its effect was found most marked when it was given directly into the cistern. However, duration of action was only transient.3. Continuous subarachnoid irrigation was found effective in reducing vasospasm. By adding a small amount of papaverine hydrochloride ( 2×10-3%), which gave far less concentration than those effectively used topically, to the perfusate the effect of relieving vasospasm was enhanced and prolonged spasmolytic effect was obtained.As a conclusion, it was important to reduce spasmogenic substances liberated from the blood clots in the subarachnoid space in order to get good and long-lasting effect in relieving vasospasm with spasmolytic agents such as papaverine, and continuous irrigation of the subarachnoid space was of value.