Sequential changes of intimal ultrastructure in experimental vasospasm induced by oxyhemoglobin were investigated by scanning electron microscope.
Twenty-one cats were used for this study. The basilar artery was exposed by transcervico-transclival approach. Oxyhemoglobin solution was applied under the arachnoid membrane around the artery in 13 cats at hourly intervals. Of 13 cats, 3 were sacrificed at 1 hour after the first application of oxyhemoglobin solution, 3 at 3 hours, 4 at 24 hours. Three sham operation cats were treated by artificial CSF instead of the solution, and with 5 untreated normal cats, used as the control. All procedures were performed under aseptic condition. Perfusion fixation was done.
In 1-and 3-hour groups, the lamina elastica was corrugated and the endothelial cells were protruded to the lumen in depressed portion of the corrugation. In 6-and 24-hour groups, regressive changes of the endothelial cells, crater-formation and ballooning, were seen. Some white blood cells adhesed to the luminal surface in such cases. In 24-hour group, endothelial cells were all protruded, and in the total aspect, the luminal surface of the endothelial layer showed cobble-stone appearances.

抄録全体を表示

The earliest report concerning the vasa vasorum of cerebral vessels was described by Gimbert in 1965, but after this there is sporadic literature in relation to whether the vasa vasorum exist in the intracranial cerebral artery or what kinds of physiological role it has. Therefore, these are now in conrtaversy over in which vessel it is distributed and how does it changes in various pathological conditions.
Anatomical feature of the vasa vasorum of the basilar artery were investigated with the stereomicroscope and the scanning electron microscope by utilizing resin-injection cast model of basilar artery. There were arterioles which ran through the adventitia in the basilar artery of dogs. These arterioles could be called the vasa vasorum. Following these preliminary experiments, the pathological changes of the vasa vasorum in subarachnoid hemorrhage were investigated using the dogs. The obtained views are as follows: (1) in the adventitia of the basilar artery of dogs, there are long branches ran longitudinally along the basilar artery trunk and short branches that transverse it. One of that is longitudinal branch originating from the caudal artery and caudal communicating artery that extended to caudal 1/3 of the basilar artery from rostral and the other originating from the caudal cerebellar artery that extended longitudinally from caudal to rostral to 1/3 of the basilar artery. Many of the transverse branches arise near the origin of the pontine arteries of the basilar branch. The transverse and longitudinal branches often cross together and form a net-like pattern. These arterioles exist in the basilar artery and its branches that have diameters of approximately over 250μ. The diameter of the longitudinal branch of the vasa vasorum was 20-50μ, the diameter of the transverse branch was 10-30μ.
During the acute stage of subarachnoid hemorrhage, these arterioles tended to disappear according to the severity of the hemorrhage, especially the transverse branch tended to disappear easily than the longitudinal branch.

抄録全体を表示

It is well known that so called vasospasm is one of the most important factors complicating the management of patients with subarachnoid hemorrhage from cerebral aneurysms.
We have made prospective and histological study of the intracranial arteries with angiographically demonstrated arterial narrowing in 6 cases. In 4 of them, the course of vasospasm was investigated by repeated angiographies. At autopsy, main intracranial arteries were carefully dissected free from the base of the brain. Serial sections were cut and stained for light microscopy and electron microscopy. The arterial wall corresponding to the angiographic vasospasm showed various structural changes.
In constriction stage, we have found contraction of the median smooth muscle cells, intimal edema due to eodothelial injuries, and thrombus formation. And, at the stage of dilatation of the arterial lumen, it was noted that there were necrosis of the medial smooth muscle cells and thickening of the intima.

抄録全体を表示

It has been revealed that the large cerebral artery adjacent to a ruptured aneurysm has not only a functional contraction but also various pathological changes of the blood vessel in the stage of late spasm. We reported previously that when the narrowing artery was recognized on a cerebral angiogram in patients with ruptured aneurysm, its histological change could be estimated by studying the appearance and frequency of electrical discharges recorded from the narrowing artery after clipping of the aneurysm.
In this study, we recorded simultaneously the isometric contraction and electrical discharge from a ring-cut bovine middle cerebral artery in organ bath by administration of serotonin and incubated bovine blood. Furthermore, we studied the relationship between the frequency of an electrical discharge induced by incubated blood and the pathological change of vascular smooth muscle after making the vessel contract continuously in incubated blood for 5 minutes, 3 hours and 6 hours.
The result was as follows; Vascular contraction induced by serotonin and incubated blood followed an electrical discharge recorded from the vascular wall. After 5 minutes of overloading of incubated blood on the vessel, the electrical discharge showed burst appearance and the histological findings of the vascular smooth muscle was considered to be nearly normal. After 3 hours, the electrical discharge showed sporadic appearance and the histological picture had partial degenerative change of vascular smooth muscle. After 6 hours, the electrical discharge was seldom or never detected and the histological picture had a diffuse degenerative change of vascular smooth muscle.
From the result of the experimental study, we were able to determine that the electrical discharge recorded from the vascular wall in patients with ruptured aneurysm is derived from vascular smooth muscle and its appearance could be regarded as the indicator of the functional reversibility of cerebral vasospasm.

抄録全体を表示

We hitherto reported that the activation of the complement system was closely related to the genesis of late cerebral vasospasm after subarachnoid hemorrhage. At present one of the useful indices for the activation of the complement system is measurement of C₁q binding IgG by C₁q solid phase enzyme immunoassay. Therefore we measured C₁q binding IgG in CSF and in serum from patients with SAH by C₁q solid phase enzyme immunoassay and examined the relationship between the activation of the complement system and late cerebral vasospasm. Thirty six CSF samples and 13 serum samples were collected from 19 patients with SAH. C₁q binding IgG was detected in 19 out of 25 CSF samples (76%) collected at the time when cerebral vasospasm was recognized.
On the other hand, only 2 CSF samples (18%) contained C₁q binding IgG in 11 CSF samples which were collected from patients without cerebral vasospasm. The difference was significant. In 13 cases C₁q binding IgG both in CSF and in serum was measured at the same time. In 5 out of 13 cases the level of C₁q binding IgG in CSF was greater than that in serum. C₁q binding IgG was not detected either in CSF or in serum in 5 of these 13 cases. This result suggested that C₁q binding IgG in CSF was not transferred from blood but was formed in the subarachnoid space. Moreover, C₁q binding IgG was detected in 17 of 23 CSF samples collected on 4-14 th day after SAH. From these data, there was close relationship between C₁q binding IgG in CSF and late cerebral vasospasm.

抄録全体を表示

Three hundred and five patients with ruptured intracranial aneurysms were analyzed to investigate the incidence and the type of vasospasm in reference to the age. Furthermore, the effect of vasospasm was disclosed upon clinical states, the development of cerebral infarction and follow-up results as related to the age. The patients were classified into three groups: A-younger than 50 years, B-from 50 to 59 years, C-over 60 years. The extent of vasospasms was classified into four types: diffuse (narrowing over 2cm in length in at least one of the C₁, A₂ and M₁ portions), peripheral (narrowing over 2cm in length in the distal portions), multi-local (multiple localized narrowing), local (single localized narrowing). The diffuse type of vasospasm was further divided into two grades of severity: diffuse severe (reduction of the caliber by more than 50%) and diffuse mild (reduction of the caliber by 25 to 50%). As an indicator of objective estimation of vasospasms, the ratio of the diameter of the arteries at the C₁, A₂ and M₁ portions to that of the canalicular portion of ICA was calculated from 32 normal angiograms (A-P projections).
The results were as follows. 1) The time course of the incidence of vasospasms was almost same in the three groups. Vasospasms were seen in only exceptional cases within 3 days after subarachnoid hemorrhage. The incidence of vasospasms increased as the time passed, reached its peak between 8th and 15th day, and then decreased gradually. Only few cases showed vasospasm over 50 days after subarachnoid hemorrhage. 2) The incidence of vasospasms 4 to 20 days after subarachnoid hemorrhage were A: 68.7%, B: 74.2%, and C: 50%, respectively. The difference between C group and other groups was statistically significant. 3) Most of the vasospasms seen 4 to 20 days after subarachnoid hemorrhage were of diffuse type in A and B groups, while only half of the vasospasm belonged to diffuse type in C group. 4) Diffuse severe and peripheral type of vasospasm had serious effect on the clinical state and outcome of the patients in C groups, while the effect was not necessarily severe in A and B groups.

抄録全体を表示

Eighty-four patients with intracranial ruptured aneurysms were analyzed to investigate the relationship of cerebral vasospasms to subarachnoid clots, to cerebral circulation and to cerebral metabolism and the effect of vasospasms upon the development of cerebral infarction.
The extent of vasospasms was classified into four types: diffuse, peripheral, multi-local and local. The diffuse type of vasospasm was further divided into two grades of severity, diffuse severe and diffuse mild. The extent of vasospasm was estimated by angiography performed 4 to 20 days after the subarachnoid hemorrhage. Measurement of the rCBF was undertaken by the intra-arterial xenon-133 injection method. The degree of subarachnoid clot was graded according to the high density area in the CT from 0 to II.
The results were as follows. 1) There was a good correlation between the degree of subarachnoid clot within 3 days after the subarachnoid hemorrhage and the types and the severity of the vasospasm. 2) Most of the patients with the diffuse type of vasospasm, especially with the diffuse severe type, showed decreases of mean CBF and impaired CO₂ response, while mean CBF of the patients with the multi-local and the local type of vasospasm showed no meaningful decrease when compaired to the patients without vasospasms. Increase of cerebrovascular resistance was seen in patients with a diffuse severe type of vasospasm. 3) The value of CMRO₂ showed a good correlation to vasospasm : diffuse mild and diffuse severe, 1.42±0.79; local and none, 2.27±0.52ml/100g brain/min. CMR glucose correlated also with vasospasm: diffuse mild and diffuse severe, 2.44±1.19; local and none, 3.26±1.20mg/100g brain/min.
4) Twenty out of 38 patients with a diffuse type of vasospasms developed cerebral infarction (12/10 severe, 4/14 mild and 4/4 peripheral), while none of the 14 patients with no vasospasm or local and multilocal type of vasospasm: developed cerebral infarctions. 5) Development of cerebral infarctions depended not only on the severity of vasospasms but also on the duration of the vasospasm and interval between onset of the vasospasm and the subarachnoid hemorrhage.

抄録全体を表示

Postoperative measurements of regional cerebral blood flow (rCBF) were performed in 27 patients with ruptured intracranial aneurysms to investigate the relation of rCBF to vasospasm and to the cerebral ischemic neurological deficits. The clinical materials were 27 patients (14 males and 13 females) who underwent the definitive surgery (clipping or coating) for their ruptured intracranial aneurysms. None of them developed the ventricular dilatation nor intracerebral hematoma.
Using Novo Cerebrograph^® with 133xenon inhalation method, rCBF studies were conducted in each patient at postoperative one and two weeks. The hemispheric mean value of initial slope index was estimated in both hemispheres. According to its extent, angiographic vasospasm was classified into four types. If a patient deteriorated neurologically in the absence of intracerebral hematoma or ventricular dilatation, the neurological deterioration was regarded as the cerebral ischemic neurological deficits due to vasospasm.
The results were as follows:
1) In both hemispheres the cerebral blood flow (CBF) of postoperative two weeks was greater than that of postoperative one week.
2) According to its extent of their angiographic vasospasm, patients were classified into four groups; nospasm, diffuse-mild, diffuse-severe and peripheral. Peripheral group showed most greatly decreased CBF in four groups. The decrease of CBF in diffuse-severe group was the next greatest. The CBF of diffuse-mild and no-spasm groups was not decreased in any hemisphere.
3) Patients who developed the cerebral ischemic neurological deficits due to vasospasm showed significantly decreased CBF in both hemispheres in comparison with those who did not develop the neurological deficits.
In conclusion there is the significant relationship of rCBF to the presence of vasospasm and of the cerebral ischemic neurological deficits, and the rCBF studies are very important for understanding the pathophysiology of vasospasm in patients with ruptured intracranial aneurysms.

抄録全体を表示

Dynamic computed tomography (CT) with intravenous bolus injection of contrast medium were performed on 5 patients under the condition of cerebral angiospasm after the rupture of intracranial aneurysms. Rapid serial scans (8 scans per minutes) were performed and the results were demonstrated as the time-density curve of any region of interest. On this study, cerebral hemispheres of both sides were chosen as the region of interest, and the time-density curves of both sides were compared.
As a result, in the case with the clinical neurological deficit, the time-density curves of both hemispheres showed a different pattern as the delayed peak and/or poor elevation of time-density curve in the lesional side. On the other hand, in the cases without clinical neurological deficit, the time-density curves showed the same pattern in both hemispheres.
Dynamic CT was non-invasive examination for the patient and its technical procedure was easy. So this study was thought to be a good method to know the brain circulation in the case of cerebral angiospasm.

抄録全体を表示

Three dimensional analyses of local carebral blood flow were made in patients with cerebral vasospasm. The instrument used was single photon emission tomography (PHO/GAMMA LFOV, E Shimazu Co. Ltd. Japan) and an on-line data processing system (Scintipac 1200). The cases comprised seven patients with cerebral vasospasm after aneurysmal surgery.
^81mKr in 5% glucose was continuously infused just above the aortic valve by means of a ⁸¹Rb-^81mKr generator.
The results were as follow :
1) Local hypoperfusions were recognized in six patients, who revealed a low density area in the affected region by follow-up XCT.
2) Local hyperemia was noticed in only one patient, who revealed hemorrhagic infarction in the identical cerebral region.
3) After hypervolemic and hypertensive therapy, overall ^81mKr activities were increased. However, local hypoperfusion was not specifically improved.
4) After hyperventilation, three dimensional display of cerebral blood flow revealed a decrease in relation to hypocarbia.
Three dimensional analysis of cerebral blood flow is useful to grasp the pathophysiology and to decide effective therapeutic principles in patients with cerebral vasospasm.

抄録全体を表示

The affect of bilateral cervical ganglionectomy was observed in basilar artery vasospasm induced by the application of Oxyhemoglobin in cats. In cases with vasospasm continued for,1 or 2 hours, basilar artery was dilatated and rCBF at white matter of pons was increased after the ganglionectomy. On the other hand, These changes after the ganglionectomy were slight in cases with vasospasm continued for 3 or 5 hours.
Clinically, the effectiveness of cervical ganglionectomy performed in early stage of vasospasm was reoprted. The findings in this report suggest it's significance.

抄録全体を表示

Histochemical fluorescent study was made on regeneration of the aminergic nerves of rat cerebral arteries after uni- or bilateral superior cervical ganglionectomy.
Regeneration started mainly from the proximal portion of the internal carotid artery between 4 and 6 weeks and reached the maximum in number between 9 and 12 months after sympathectomy.
The number of maximally regenerated nerves was about half of that in normal rats.
Regenerated aminergic nerves were generally unbeaded and the intensity of fluorescence was weak.

抄録全体を表示

Prazosin, a new α₁-receptor blocking agent, was investigated for releasing and preventing effect on experimental cerebral vasospasm induced by oxyhemoglobin.
Four cats were treated by Prazosin before induction of vasospasm by oxyhemoglobin (pre-treatment group), and 6 cats were treated after (post-treatment group). In the pretreatment group, prevention of vasospasm was observed. In the post-treatment group induced vasospasm was released from 2 hours after administration of Prazosin.
The mechanism of preventing and releasing effect of Prazosin on cerebral vasospasm was discussed.

抄録全体を表示

Despite the importance of cerebral angiospasm, we are still limited in our knowledge of the mechanisms involved in this phenomenon. Although it has been reported that denervation supersensitivity may be one of the causes of cerebral angiospasm, actually the cause of this phenomenon is still unconfirmed.
In the present experiments, changes in the reactivity of rabbit basilar artery to noradrenaline, serotonin and potassium ion after bilateral superior cervical sympathectomy were studied. 1. Fluorescent micrograph showed disappearance of noradrenaline from nerve fibers and terminals, seven to fourteen days after sympathectomy.
The noradrenaline content of basilar artery was reduced to 140.5±71.9 ng/g wet tissue (M±SE, n=6) seven days after ganglionectomy, and 137.8±49.8 ng/g wet tissue (M±SE, n=6) fourteen days after operation. Control: 2000.7±183.2 ng/g wet tissue (M±SE, n=11).
2. Seven days after operation, sensitivity of the basilar artery to noradrenaline increased. The threshold concentration was fell to 5×10^-8 M as compared with that of control (5×10^-7 M), while the maximum tension observed at a concentration of 5×10^-4 M of noradrenaline increased to about 1.5 fold of that of control.
In a similar manner, the sensitivity to serotonin also increased, and the threshold concentration fell to 5×10^-10 M (control: 5×10^-9 M). The maximum tension increased about 1.7 fold of the control The response to 24.3 mM K was increased to about 1.7 fold of the control.
These results showed that after denervation, supersensitivity of rabbit basilar artery occured. The present experiments also indicate the possibility that denervation supersensitivity may be one of the causes of cerebral angiospasm.

抄録全体を表示

Electrolytes which are known to have vasomotor effects have not been well evaluated as to their possible role in the induction of vasospasm.
Present study was undertaken to clarify some contributions of electrolytes, especially potassium ion which are liberated in the process of hemolysis of the blood clot.
The basilar arteries of adult rats were used. Under pentobarbital anesthesia the basilar arteries were exposed by transclival approach under the operating microscope. Subarachnoid hemorrhage was induced by puncture on a small branch artery with a: fine needle. In each of 10 minutes, two hours, and 24 hours after subarachnoid bleeding, the fresh arterial strips were removed and the specimens were immediately frozen in liquid nitrogen, cryosectioned at -120°C and freeze-dried at -85°C. Electron probe X-ray microanalysis of drycryosection was performed to determine the elemental compositions of extravasated erythrocyte and periarterial space. The K concentration was increased in the extracellular space to 8 times above the baseline in 24 hours after subarachnoid bleeding. The K concentration of extravasated erythrocyte was decreased in 24 hours.
Time course of potassium ion liberation from extravasated erythrocytes was also reported. The hypertensive intracerebral hematomas were collected during surgery. By the flamephotometer, K concentrations of supernatants of the hematomas were measured chronologically. On the other hand, peak of potassium ion level in the intracerebral hematoma is reached around the third or the fourth post hemorrhagic day, and the level is gradually reduced to normal approximately in three weeks.
Potassium has been known to have potent vasomotor effects but the importance of this ion has not been well appreciated. It is obvious from our present study that ionic environment is of cardinal importance in development of vasospasm and especially potassium should be reevaluated in its possible role for cerebral vasospasm caused by subarachnoid hemorrhage.

抄録全体を表示

In vitro experiments were performed using small volume chambers (50ml) to evaluate the contractile activity of the canine basilar and femoral arteries. The contractile activity of the basilar arteries were very different from the femoral arteries. Calcium-release contractions of the basilar arteries which were produced in calcium-free buffer solution were lower than the femoral arteries. Potassium (60 mM) ions induced substantial contractions to the femoral arteries even in calcium-free solution, but none to the basilar arteries.
On the other hand, postglandin F_2α and serotonin acted additively on the basilar arteries in both of the calcium release and the maximal contractions, but not on the femoral arteries.
The basilar arteries needed the minimal concentration of 10^-5 M calcium ions in buffer solution for contractions induced by serotonin. And also, if pretreated with high concentration of calcium ions (10mM), calcium release contractions of the basilar arteries were significantly increased. Concerning contractions of the basilar arteries, it seems likely that influx of calcium ions through the cell membrane of vascular smooth muscle depends predominantly on the receptor-operated channels and in the femoral arteries the potential-sensitive channels play main role on influx of calcium ions for their contractions. Also extracellular concentration of calcium ions which is necessary to induce contractions of the basilar arteries is about 100 folds of the intracellular calcium ions.

抄録全体を表示

Total Ca and Ca⁺⁺ in cerebrospinal fluid were measured from the patient with subarachnoidal hemorrhage due to ruptured cerebral aneurysm. Relationship was studied between the values of total Ca and Ca⁺⁺ and grades of cerebral vasospasm on cerebral angiograms. Additionally, experimental studies were performed on helical strip of dogs' basilar arteries with constrictable substances such as KCI and oxy-hemoglobin(Oxy-Hb).
Findings were as follows:
1. There was a gradual increasing of vasospasm in the patients whose cerebrospinal fluid contained high values of total Ca at one or two days after rupture of aneurysm.
2. In all samples of bloody cerebrospinal fluid, values of Ca⁺⁺ were almost the same or lower than that of control group. The time course of Ca⁺⁺ concentrations was remarkably decreased in the group with increased vasospasm.
3. In the experimental study, continuous constriction of helical strips were induced with high concentration of KCI and physiological values of Oxy-Hb. The effects of KCI and Oxy-Hb were remarkably inhibited when Ca⁺⁺-antagonist was added to the artificial cerebrospinal fluid or Ca⁺⁺ was freed from the fluid.
With these results, it was thought that Oxy-Hb might be the most important substance for cerebral vasospasm and it may affect cerebral vessels with Ca⁺⁺ in cerebrospinal fluid. It was, however, an unreasonable result that time course of Ca⁺⁺ decreased on the patients with severe vasospasm when vasospasm were increased. Then, high concentration of total Ca at acute stage after subarachnoidal hemorrhage were considered as it may trigger the incidence of cerebral vasospasm.

抄録全体を表示

Effect of Ca⁺⁺ antagonist (nifedipine) on experimental and clinical vasospasm was examined. In experimental animals, vasospasm was produced by dripping BaCl₂ solution on the middle cerebral artery. After topical application of BaCl₂, the cerebral arteries revealed severe vasospasm for 40 min. Regional cerebral blood flow, measured with H₂ clearance method, markedly decreased during the vasospasm. Nifedipine, administered systemically 10 min after BaCl₂ dripping, caused vasodilatation and increase of regional cerebral blood flow.
In clinical study, nifedipine (70-160mg/d) was administered systemically 7 patients with vasospasm. Fifteen minutes after nifedipine administration, A₁ and C₁ portions of cerebral arteries revealed vasodilatation (C₁: 25% and A₁: 11.4%) on carotid angiographies. Clinical symptoms and signs resulted from cerebral vasospasm disappeared in 6 out of 7 patients after nifedipine treatment.
Nifedipine exerted excellent effect in patients with mild to moderate vasospasm, but no effect in patient with severe vasospasm.

抄録全体を表示

Experimental delayed vasospasm was produced by topical application of a 3-day-old incubated blood-CSF mixture on the feline basilar artery which was exposed transclivally on the third day after the injection of blood into the cisterna magna. The effect of calcium antagonists on both rCBF in the brain stem and arterial blood pressure was studied. rCBF was measured by heat clearance method.
Intravenous administration of nifedipine, nicardipine, verapamil, cinnarizine and diltiazem produced mild to moderate hypotension in a dose of greater than 0.003, 0.01, 0.2, 0.65, 0.07mg/kg respectively.
A prolonged increase of rCBF was observed in 43% of the cats with mild hypotension induced by nifedipine. Nicardipine and verapamil also demonstrated the prolonged increase of rCBF in 18% and 6% of the cases respectively. When moderate hypotension was produced by each of calcium antagonists, a prolonged increase of rCBF was noted in 25% of the cases treated with nifedipine, 18% with nicardipine, and 43% with verapamil. Cinnarizine and diltiazem showed only a transient increase of rCBF which lasted no more than 10 minutes.
These results indicate that calcium antagonists used in this study may act mainly on the extracranial rather than intracranial vessels. Further study is required to apply these chemicals for patients with cerebral vasospasm.

抄録全体を表示

Nimodipine (Nimo.) is Ca-antagonist which is considered to have a vasodilating effect on cerebral arteries. Authors studied the vasodilating effect of Nimo. on human cerebral arteries in 22 cases with ruptured intracranial aneurysms. Studies consisted of two steps. In the first step, 0.004% Nimo. was topically administered to cerebral arteries during aneurysmal surgery (3±1 day after onset). In the second step, 200μg of Nimo. was topically administered via cisternal drainage tube postoperatively (8±3 days after onset), and cerebral angiography was carried out to evaluate the changes of arterial diameter. Among those postoperative cases, 6 cases were administered additional 200 μg of Nimo. intravenously at the same time.
In the first step, non-spastic cerebral arteries were dilated by Nimo. in almost all cases. In the second step, non-spastic arteries also dilated in 3 of 4 non-spastic cases. But, vasospastic arteries dilated only in 5 of 15 cases, and those effective cases were in the early stage from the appearance of mild to moderate vasospasms. Furthermore, the dilating ratio was higher in cases with both intracisternal and intravenous administration of Nimo.
From those results, it is considered that Nimo. may be able to prevent the appearance of vasospasms, but the method of administration must be studied in the future.

抄録全体を表示

The mechanism of action of Ca²⁺ antagonists, such as verapamil and nifedipine, has been postulated to be a blockade of transmembrane calcium influx.
In this study, the vasodilating effect of diltiazem on experimental cerebral vasospasm in vivo was examined using dogs and compared with those of cinnarizine, verapamil and nifedipine which have already been reported by us. Cerebral vasospasms were induced in adult dogs by injecting 5 ml of fresh arterial blood into the cisterna magna. 10^-6M diltiazem was injected by one shot into the vertebral artery of the dogs with cerebral vasospasm. Dilatation of the cerebral arteries was observed by angiography after administration of diltiazem. Blood pressure, intracranial pressure and pulse rate were measured during intravenous application of the drug in normal dogs.
Administration of diltiazem released the vasospasm for 30 minutes, comparable to the times of the other Ca²⁺ antagonists. Diltiazem had cerebral vasodilator actions similar to cinnarizine at doses that did not decrease systemic blood pressure, while the other drugs increased intracranial pressure slightly. Therefore, we consider diltiazem to be satisfactory for the treatment of experimental cerebral vasospasm.

抄録全体を表示

Experimental subarachnoid hemorrhage was produced by an intracisternal injection of fresh autologous arterial blood in 33 cats. Three days later the basilar artery was exposed transclivally and further advanced prolonged vasospasm was produced by topical application of blood-CSF mixture incubated at 37°C for three days. Regional cerebral blood flow (rCBF) in the brain stem was measured by means of heat clearance method. Arterial blood pressure in the femoral artery was also monitored continuously. Intravenous administration of either PGI₂ or OKY-1581 (a specific inhibitor of thromboxane A₂ synthetase) produced a decrease of arterial blood pressure. The changes of rCBF were divided into three types: Type A consisted of those with no changes. Type B was related to the arterial blood pressure. Type C showed increase in rCBF despite of systemic hypotension.
Type A or B in rCBF was observed in 17 out of 19 cats in which PGI₂ was administered intravenously, and Type C was observed in only 2 cats. Comparative study was done in 13 control cats in which had neither subarachnoid hemorrhage nor topical application of blood-CSF mixture. Type A or B was shown in 12 and Type C was in only one cat. From these results, PGI₂ was likely to dilate extracranial rather than intracranial vessels regardless of cerebral vasospasm.
OKY-1581 was administered in 14 cats with cerebral vasospasm and in 10 control cats. Type C pattern was demonstrated in 10 cats with vasospasm and in 7 of the control cats.
Though OKY-1581 produced the increase of rCBF in most of normal cats and those with cerebral vasospasm, its action did not seem to be due to the increase of PGI₂ synthesis by inhibition of TXA₂. synthesis. OKY-1581 might be useful in prophylaxis and treatment of ischemic syndrome due to cerebral vasospasm.

抄録全体を表示

Experimental cerebral vasospasm was produced by an intracisternal injection of fresh autogenous arterial blood in the dog. The changes of caliber of basilar artery, regional cerebral blood flow (rCBF), mean arterial blood pressure (MBP), and pulse rate (PR) at 30 torr of PaCO₂ were examined during a continuous intravenous infusion of OKY-1581, a pyridine derivative, a selective inhibitor of thromboxane A₂ synthesis.
No significant changes were founded in caliber of basilar artery, MBP, and PR of normal and spastic animals by OKY-1581 infusion at 20 or 50 μg/kg/min for 1 and 2 hrs. The mean rCBF increased significantly in spastic animals when OKY-1581 was infused at 20 or 50μg/kg/min for 2 hrs. It would be suggested that OKY-1581 infusion might improve symptomatic cerebral vasospasm.

抄録全体を表示

The efficacy of thromboxane synthetase inhibitor in the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH) was evaluated in a prolonged experiment using dogs. Changes in the diameter of the basilar artery were followed by angiography and morphological changes were studied by photomicroscopy and electron microscopy. As a thromboxane synthetase inhibitor, OKY-1581 (sodium (E)-3-(4(-3-pyridylmethyl)phenyl-2-methylate) was used.
After subarachnoid blood injection, dogs received intravenous injections of OKY-1581 until sacrifice four days after induction of SAH. The control dogs received subarachnoid blood injection without treatment with OKY-1581.
Angiographical examination revealed that the late spasm was almost completely abolished by the treatment with OKY-1581. The early spasm was also prevented, but the drug's effect was less prominent than it was on the late spasm. Morphological study revealed degenerative changes in the endothelium and myonecrotic changes in tunica media following SAH in the basilar arteries of the treated as well as the untreated dogs. However, corrugation of the internal elastic lamina was almost completely absent in the treated dogs.
The above results indicate that a disproportionate synthesis of thromboxane A₂ plays an important role in the evolution of chronic cerebral vasospasm following SAH and that drugs such as OKY-1581 that selectively inhibit thromboxane synthetase might be useful in the prevention of vasospasm.

抄録全体を表示

Recent studies have demonstrated that cerebral ischemia with vasospasm is an important factor to determine outcome after rupture of intracranial aneurysm. The cerebral ischemia may be caused by decrease of prostacyclin (PGI₂) and increase of Thromboxane A₂ (TXA₂) which promote platelet aggregation and vasoconstriction.
Thromboxane A₂ inhibitor was used as preventive agent for ischemia with cerebral vasospasm. Clinical trial was made of 37 cases who had ruptured aneurysm within 7 days after subarachnoid hemorrhage. OKY-1581 (270-300mg/day) was intravenously or orally administrated about 2 weeks after admission_Patients were classified 4 Groups by Fisher's Classification. 24 cases of Group 1-3 were operated.
Outcome of 15 cases of Group 1 to 2 which show none or slight diffuse subarachnoid clot demonstrated good recovery except only one case. 10 cases of Group 3 which show clot or thick layer subarachnoid hemorrhage demonstrated excellent results except 2 cases who had neurological deficit. Ischemic signs during 2 weeks after OKY administration had not been observed in cases of Group 3 except only one case.
This case was died by severe infarction with vasospasm. These results suggest that Thromboxane A₂ inhibitor may be an effective agent as prevention of cerebral ischemia with vasospasm.

抄録全体を表示

It is well known that superoxide dismutase (SOD) acts on free radical reactions at their early stage as a scavenger against superoxide. On 17 cases with ruptured intracranial aneurysms, we studied the.changes of SOD activities in the cerebrospinal fluid. All patients were operated on within four days after the onset, and CSF samples were taken from both the lateral ventricle and the chiasmatic cistern for seven to ten days after surgery. The results were compared with the changes of the amount of lipid peroxide in CSF during the same period and with the presence or absence of postoperative vasospasms. From the patterns of the changes of SOD activities, patients were divided into three groups; in seven. cases, the level of SOD activities in both ventricular and cisternal CSF started to decrease on the third clay after the onset and fell to almost null on the fourth day and thereafter (severly decreased group), in eight cases, SOD activities remained within normal ranges thoughout the period (nornal range group), in the remaining two, the level of SOD activities decreased moderately either in ventrcular or cisternal CSF (moderately decreased group). In the severely decreased group, all but one had a large amount of lipid peroxide in CSF on the fourth day and afterward. They showed an evidence of angiographically severe vasospasm and clinical deterioration. In all patients in the normal range group, the level of lipid peroxide in CSF was low throughout the period. They had good clinical courses and no postoperative angiospasm. One patient in the moderately decreased group had a high level of lipid peroxide while the,other's remained low. Both showed angiographic vasospasm without developing clinical symptoms.
It was concluded that superoxide dismutase in CSF as a scavenger might play an important role in protecting cerebral vessels against vasospasm in patients with ruptured intracranial aneurysms.

抄録全体を表示

Experimental investigation was performed on oxyHb induced vasospasm (VS) and on effect thereon of ascorbic acid (AsA) pretreatment. Following results were obtained.1) AsA was found to inhibit lipid peroxidation significantly in incubated erythrocyte suspension. It also inhibited auto-oxidation of oxyHb in hemolyzed fluid. 2) Amount of hemolysis, which occured in erythrocyte suspension during 3 day's incubation, was decreased by pretreatment with AsA. 3) Vasoconstricting activity of incubated hemolyzed fluid by AsA pretreatment was reducted significantly. 4) AsA was found to facilitate non-oxidative degradation of oxyHb.
The degradation was supported to proceed from protoheme, through choleheme to verdoheme. Clinical trial on prevention and relief of postoperative VS was justified on account of above experimental results 56 patients with aneurysmal rupture were operated during last year, were devided in 3 groups. 17 patients operated after day 15 (the day of haemorrhage was day 1) into Group 1, 15 patients operated within day 4 without intracisternal AsA administration into Group 2, 24 patients operated within day 4 with intracisternal AsA administration were classified in Group 3 respectively. Effect of intracisternal AsA administration ws appreciated from standpoints of pre and postsurgical CT (clot score), carotid angiogram (Grade of VS) and surgical result one month later (ADL). Surgical result and grade of VS were more favorablein Group 3 than Group 2. Intracisternal AsA administration to the patients, who have been detected high clot score in postsurgical CT, seems to be more reasonable and effective in particular.

抄録全体を表示

It has been recently reported that chronic vasospasm is caused by free radical injury after subarachnoid hemorrhage. Since alpha-tocopherol is one of the free radical scavengers, effect of intrathecal use of alpha-tocopherol was evaluated experimentaly.
Twenty adult dogs were used for these study. These dogs were equally divided into subarachnoid hemorrhage (SAH) group and SAH+ alpha-tocopherol group. SAH was made by intrathecal injection of 5 ml of auto-blood with 2 ml of normal sailine into cisterna magna in SAH group. (10 dogs). Two ml (100mg) of alpha-tocopherol was injected instead of the same amount of normal sailine in SAH+ alphatocopherol group. (10 dogs).
1) Diameter of basilar artery (BA) and posterior cerebral artery (PCA) was measured on angiogram which was taken before and 24 hours after SAH. BA and PCA in SAH+ alpha-tocopherol group were dilatated 24 hours after SAH compared with these before, while these arteries in SAH group became narrower. (P<0.01)
2) Animal's condition was examined after SAH as below.
stage 0: the same as the condition before SAH.
stage 1: moving actively.
stage 2: sitting only.
stage 3: lying down. In SAH+ alpha-tocopherol group 7 dogs were in stage 1 and 3 dogs were in stage 2 after SAH, while 6 animals were in stage 3, 3 in stage 2, 1 in stage 1 in SAH group.
3) Every cases were examined pathologically, which showed endotherial degeneration and edema, constriction of internal lamina, and edema and vascular degeneration of the media in SAH group. But only mild constriction of internal lamina was found in SAH+ alpha-tocopherol group. Therefore intrathecal use of alpha-tocopherol seems to have preventive effect of chronic vasospasm experimentally.

抄録全体を表示

Management for treatment of subarachnoid hemorrhage in acute stage is still controversial. One of the most important factors in the acute stage is chronic vasospasm. There are many different theories about the pathogenesis and treatment of chronic vasospasm.
Recently we can prospect the occurrence of the symptomatic vasospasm by CT findings. Therefore we evaluate the effect of intrathecal use of alpha-tocopherol to prevent the symptomatic vasospasm on these cases.
Alpha-tocopherol (50-100 mg) were injected into subarachnoid space in 23 cases, including 15 cases with early operation and 8 cases with delayed operation. In cases with early operation, cisternal drainage was put into parachiasmatic cistern, and 100 mg of alpha-tocopherol was injected via the drainage tube every day for 2 weeks. In cases with delayed operation 100 mg of alpha-tocopherol was injected via spinal tap or ventricular drainage if CT revealed hydrocephalus. Occurrence of symptomatic vasospasm was evaluated in these 23 cases compared with that in cases without use of alpha-tocopherol as a control.
Occurrence of symptomatic vasospasm in control group was 3% in gr 0, 7% in 1, 4% in gr 2, 45% in gr 4, 83% in gr 4. However, occurrence of symptomatic vasospasm in cases used alpha-tocopherol was 0% in gr 0 and 1, 11% in gr 2, 20% in gr 3, 40% in gr 4.
Therefore, symptomatic vasospasm cccurred almost half in cases used alpha-tocopherol compared with control group.

抄録全体を表示

Vasoconstrictor agents in cerebrospinal fluid (CSF) obtained from patients sustaining subarachnoid hemorrhage (SAH) was investigated by attempting to reverse the CSF-induced contraction with specific pharmacological antagonists, disulfide-reducing agents and OH scavenging agent, 1,2-Bis (nicotinamido)-propane (AVS).
The CSF-induced contraction of is olated canine basilar artery was not reversed by methysergide, mepyramine, phenoxybenzamine, propanolol and atropine. Therefore, serotonin, histamine, norepinephrine or acetylcholine were eliminated as prime vasoconstrictor agents in CSF.
Dithiothreitol or dithioerythritol (disulfide-reducing agents) inhibited the CSF-induced contraction. This inhibition was achieved under conditions which did not alter KCL-induced contraction of canine basilar artery strips. These findings might suggest that oxyhemoglobin, lipid hydroperoxides or prostaglandins play a role as prime vasoconstrictor agents in the CSF obtained from SAH patients.
1,2-Bis (nicotinamido)-propane showed inhibitory effect against the CSF-induced contraction of isolated canine basilar artery strips.
This drug might be useful in the prevention of cerebral vasospasm following SAH.

抄録全体を表示

An investigation of vasospasm as seen angiographically after the onset of subarachnoid hemorrhage was carried out on 68 cases of intracranial aneurysms. The incidence of vasospasm, without regard to the length of time from repture of the intracranial anuerysm untill performance of angiography was 29%. The CT findings of these 68 cases were divided into five types as follows.
Type I: Subarachnoid hematoma could not be detected when CT was performed.
Type II: Subarachnoid hematoma was detected.
Type III: Subarachnoid hematoma with intracerebral hematoma.
Type IV: Subarachnoid hematoma with intraventricular hematoma.
Type V: Subarachnoid hematoma with intracerebral and intraventricular hematoma.
Correlation with CT types above mentioned and vasospasm was investigated, and some results could be obtained.
(Result)
1. The more the volume of subarachnoid hematoma, the higher the incidence of vasospasm.
2. The cases of type III, IV and V had a higher incidence of vasospasm than the cases of type I and II.
3. With regard to grade of vasospasm, the cases of type V were more severer than the cases of type I and II.

抄録全体を表示

Vasospasm is one of the most important factors to treat the subarachnoid hemorrhage. If we can predict the occurrance of vasospasm, the prognosis will be made clear on acute stage, and the management of subarachnoid hemorrhage will be clearer.
CT revealed the location and volume of the hematoma. The purpose of this paper is clarify the occurrence of vasospasm from the view point of CT findings and neurological grading, and then to evaluate the timing of surgery.
281 cases of aneurysmal surgery were carried out in our hospital from September 1976 to March 1981. 155 cases of grade I-IV of Hunt and Hess grading, who were operated on by the same neurosurgeon, were made on object of this study.
(Method) Hematoma in the basal cistern was classified into 5 degree with reference to the location and volume of the hematoma in the basal cistern and Hounsfield number. The disappearance of hematoma from basal cistern was examined following by CT day by day. The relation between vasospasm and hematoma in the basal cistern compared with neurological grading were evaluated. Then timing of the operation were studied.
(Results) Hematoma in grade 1 and 2 disappeared from the basal cistern within 4 days, however hematoma in grade 3 and 4 remained over a week. The occurrence of vasospasm was more related to the grade of hematoma in the basal cistern than neurological grade of Hunt and Hess.
Vasospasm occurred less in cases with early operation within 24 hours after onset than in cases with later operation after 24 hours.

抄録全体を表示

One hundred eight patients who were operated on within 4 days after acute subarachnoid hemorrhage are included in this study. All patients underwent preoperative computed tomographic (CT) scanning, and the amount and distribution of subarachnoid blood clot were noted. Operation was carried out by the frontobasal lateral approach, and the subarachnoid clot was removed by microsurgical suction-irrigation after clipping of the aneurysm. Immediate postoperative CT scanning was performed to evaluate the completeness of the subarachnoid blood clot removal. The presence or absence of postoperative vasospasm was determined with angiography performed between the 5th and 14th postoperative days. All patients were, of course, also evaluated for evidence of neurological deterioration. The postoperative CT scans showed that it was possible to remove the majority of the blood clot except that located in the frontal interhemispheric fissure, the posterior part of the insular cistern on the approached side, and all of the insular cistern on the contralateral side. There was no spasm or only mild spasm in any site where the blood clot had been successfully removed. Delayed neurological deficits occurred only in those cases in which subarachnoid blood clot remained in the cisterns. These results suggest that it is possible to prevent intracranial arterial spasm and associated neurological deterioration by early operation and removal of clotted blood from the subarachnoid space.

抄録全体を表示

Although the effectiveness of the operation of ruptured cerebral aneurysm within 48 hours after bleeding has been reported, some cases result in failure on account of post-operative vasospasm. In our clinic, 46 cases underwent the operation of cerebral aneurysm within 48 hours; of these 10 cases became worse after recovery of consciousness. In these patients the CT scan showed remarkable high density areas within the ambient and quadrigeminal cisterns.
On the basis of our data, we have investigated the effectiveness of the active removal of subarachnoid clot and the irrigation during operation so as to improve the clinical results of serious cases.
After neck clipping of cerebral aneurysm, the clot in Sylvian fissure and the basal cistern is removed as much as possible. In the serious cases, a drain is inserted into the interpeduncular cistern and the edge of the tentorium is excised after retracting the temporal lobe. The clot in ambient-quadrigeminal cistern is removed and then a drain is inserted. Drainage is performed from the interpeduncular cistern following the injection of physiological saline to the ambient-quadrigeminal cistern.
Of 6 cases in this series, 3 did not have vasospasm. And the degree of vasospasm which was recognized in 2 seemed to be reduced.

抄録全体を表示

Since 1978, we started the trial of the ultra-early operation and the additional repeated cisternal irrigation for the severe subarachnoid hemorrhage, namely intracranial aneurysm of grade 4 and 5, in order to prevent the later complication of vasospasm. In these 4 years, 148 cases of intracranial aneurysm were admitted in our hospital, in which 57 cases belonged in grade 4 and 5 (39%). In these severe cases, surgery was indicated for 38 cases and other 19 cases were not indicated for surgery. In the operative results in 38 cases, 9 cases recovered to ADL-1, 8 cases returned to ADL-2, 3 cases to ADL-5 and 15 cases died. Results of non-operative cases were miserable, or all died except one case.
Repeated cisternal irrigation was adopted in 17 cases of the operative group and as the results, 6 cases of them recovered to ADL-1, 2 cases to ADL-2, 3 cases to ADL-5 and 6 cases died; in other words, results were divided clearly into the effective group and the non-effective group.
On the investigation from the daily diminution of CT number of the basal cisterns, the following characteristic evidence became apparent in each group. 1) In non-operative cases, the daily diminution of CT number was minimal even until 6 days after the hemorrhage and the density was more than 1.5 times higher than the control brain tissue. 2) In the irrigation effective cases, the density was decreased to less than 1.5 times of the control until 3-6 days after the hemorrhage. 3) In the irrigation noneffective cases, the density was once decreased remarkably after the operation but it remained in the level of more than 1.5 times higher than the control.

抄録全体を表示

During the last two years (1981-1982), we experienced 105 cases of early operation for verified intracranial ruptured aneurysms. We made a new ventriculo-cisternal irrigation system for the purpose of washing away subarachnoid clots and diluting vasospasmogenic substances. The pathway of CSF during irrigation was confirmed by RI cisternography injecting ¹¹¹In DTPA 1 mCi into the lateral ventricle.
We applied this system to 25 cases in the 105 cases. In Grade III and W cases (Hunt & Kosnik) operated upon within 3 days after SAH (onset day=1st day), delayed ischemic deficit (DID) was found 36% and good and excellent cases were 64.3% of 14 cases with irrigation. DID was found 51.3% and good excellent cases were 30.8% of 39 cases without irrigation. Mortality rate was 21.4% with irrigation and 56.4% without irrigation. We measured the amount of fluid washed out and the concentration of Hb in 9 cases, and found that by this system about 30ml of whole blood was eliminated from subarachnoid space within 1 week in case of mild SAH, about 80ml in case of severe SAH.
This new ventriculo-cisternal irrigation system is safe and effective to prevent vasospasm and improve the prognosis of ruptured aneurysms.

抄録全体を表示

In 41 cases of ruptured intracranial aneurysms, combined ventriculo-cisternal drainage and cisternal drainage designed by us was performed after clipping of aneurysms within 48 hours after hemorrhage and the bloody cerebrospinal fluid in the basal cisterns were analyzed.
Mortality rate in this series was 9.3 per cent and symptomatic vasospasm were appeared in 7.3 percent. Out flow cerebrospinal fluid from bilateral cisterns was 300-500ml/day. Total hemoglobin in cerebrospinal fluid within one week after operation was 7.0±3.6g/dl which correspond to 46.7±23.7ml of blood. Lipoperoxide and Vit. E decreased after hemorrhage correlatively having no influence on cerebral vasospasm. Hydrogen ion concentration in the bloody cerebrospinal fluid decreased in all cases.
It may safely be concluded that the ventriculo-cisternal drainage is effective for prevention of cerebral vasospasm.

抄録全体を表示

The effect of subarachnoid clot evacuation for the prevention of vasospasm (VS) in the acute stage was studied using 121 ruptured IC, MC and A co aneurysm cases. All cases were admitted within 3 days after the onset. Cases with intracerebral hematoma, a morbibund appearance or with a troubled operation were not included in this study.
Operative procedure and extent of subarachnoid clot evacuation were as follows. In IC and MC aneurysms, extensive clot evacuation from proximal portion of M2, entire M₁ and proximal portion of A₁ to prepontine cistern by opening Liliequist's membrane were done by the transsylvian approach. But, minimal clot removal necessary for neck clipping were sometimes done in IC and MC aneurysms. In A co aneurysms, clot removal only around the A co complex were our routine procedure by the interhemispheric approach.
Extensive clot evacuation by transslyvian approach from proximal portion of M₂ to prepontine cistern within 48 hours after the onset did not prevent development of VS but might reduce the severtiy of VS. But, this tendency was not significant statistically.
Complications of excessive clot evacuation applied to the angry, swollen brain in the acute stage were identified in 4 cases. These were worsening of the brain swelling, formation of an intracerebral hematoma and an infarction of the territory of perforating artery due to too much brain compression or injury to small veins and perforating arteries.
The extent of clot evacuation should be determined by the brain's condition during the operation.It must not be done to worsen the brain's condition by the excessive clot evacuation in the acute stage.

抄録全体を表示