Erythrocyte deformability was determined in 20 patients with cerebral vasospasm. The patients were divided into two groups according to degree of vasospasm, one with severe cerebral vasospasm, the other with mild cerebral vasospasm. Erythrocyte deformability, determined by modified Reid's method, was expressed as the variability of red blood cells (VRBC). Impaired deformability of erythrocytes is not specific for cerebrovascular disorders as this phenomenon has also been reported in peripheral vascular disorders. Decrease of erythrocyte deformability may be indicative of the existence of ischemia and/or lesions in some part of the body. In this study, we confirmed that erythrocyte deformability decreased with advancing the degree of cerebral vasospasm. There were significant differences (p<0.005) in VRBC in patients with severe cerebral vasospasm and in those with mild cerebral vasospasm. A previous study showed that pentoxifylline reduced platelet and erythrocyte aggregation, enhanced energy charge potential of the cell, and reduced blood viscosity. 13 patients received 300 mg pentoxifylline intravenously for 11 days and erythrocyte deformability was measured before and after this treatment. After treatment with pentoxifylline, erythrocyte deformability tended to increase in these patients.

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Fluosol-DA, 20% is a newly developed perfluorochemical emulsion and proved to be effective on the experimental cerebral ischemia. A total of 51 administrations of the solution was performed in 24 patients suffering from symptomatic cerebral vasospasm due to ruptured aneurysms. Their neurological conditions were evaluated before and after the intravenous infusion.
Fifteen cases (62%) out of twenty four (25/51 times of administration) showed improvement of disturbed consciousness and/or motor weakness which continued for about 24 hours after the administration. The cases with anterior communicating artery aneurysms had better improvement ratio (10/11 cases, 16/24 times than those with aneurysms located in the other regions (5/13 cases, 9/27 times). The solution was considered to be more effective to improve motor weakness (13/27 times) than disturbed consciousness (18/49 times). In some cases, marked increase of cerebral blood flow or appearance of a wave on EEG was observed in accordance with the improvement of the condition.
From these clinical data, Fluosol-DA, 20% is considered to be one of the effective treatments to improve cerebral ischemia due to vasospasm.

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Perfluorochemicals (Fluosol-DA 20%), which is 0.1μ t in an average particle size and a high oxygen carrier, may be able to reach cerebral ischemic region and to improve its microcirculation.
Sixteen patients with intracranial ruptured aneurysm which had postoperative cerebral vasospasm, were treated by the intravenous administration of Fluosol-DA between February, 1981, and February, 1982. There were 8 males and 8 females, with an average of 50.4 years (range 15 to 69 years). On the all patients who were employed 1500ml of Fluosol-DA in total, nine cases were given 500ml/day (7.1 to 11.6ml/kg) daily for three days and, seven cases were given 1000ml (16.6 to 20.8ml/kg) at the first day and 500ml (8.3 to 10.4ml/kg) at the second day.
Clinical efficacy could mainly estimated by changes of consciousness level according to 3-3-9 formula and muscle testing (grade 0-5), including the findings of EEG and angiography seven days after the administration. Improvement of consciousness level and/or muscle testing, which had more than two grades, occurred in 75% of 12 cases among 16 cases. There were no side effects for the agents.
It was suggested that Fluosol-DA had a beneficial effect on focal cerebral ischemia caused by vasospasm following subarachnoid hemorrhage.

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Authors report a series of 20 cases of ruptured intracranial aneurysms followed by cerebral vasospasm manifesting neurological deficits.
These patients were treated with 20% Mannitol and Angiotensin II-induced hypertension immediately after the appearance of the symptoms of vasospasm.
15 out of 20 patients were fully recovered, 3 incompletely, and 2 remained unchanged.
In conclusion, we believe the method reported to be useful in the treatment of cerebral infarction due to vasospasm, especially in its acute stage.

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In order to avoid cerebral infarction, Volume Expansion and Hypertension Therapy (VEHT) was performed to the patients with vasospasm which occured following aneurysmal neck clipping in the acute stage of SAH.
When vasospasm was confirmed by postoperative angiography in the patients with motor and/or conscious disturbance, they underwent VEHT for about 10 days until neurological deficits were subsided. Hypertension up to 160-180mmHg in systolic blood pressure was brought by i. v. administration of whole blood and/or serum until central venous pressure elevased to 8-15 cmH₂O, and then followed by continuous injection of diluted dopamine to increase systolic blood pressure up to 200mmHg if necessary. Cardiac function was assessed carefully with Swan-Ganz catheter to prevent heart failure. Aquaous pitressin was used to control polyuria induced by volume expansion and dopamine administration. Dextran 40 and Urokinase were used to ameliorate cerebral microcirculation.
From Aug. 1980 to Jan. 1982, we performed 26 aneurysmal neck clipping in the acute stage after onset of SAH. Among them, 6 patients showed angiographical evidence of vasospasm associated with neurological dificits. They were treated with VEHT immediately after the onset. Four patients whose worst neurological signs during vasospasm were coma and/or hemiparesis well responded to VEHT and their ADL was “excellent” at discharge. A patient did not respond to VEHT. Another patient to whom VEHT was interrupted by heart failure left hemiparesis.
VEHT to the postoperative cerebral vasospasm following aneurysmal neck clipping in the acute stage of SAH is effective as long as cardiac function is examined carefully.

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Effectiveness of dopamine- or dobutamine-induced hypertension therapy (DIH) was studied in thirty patients who developed symptomatic vasospasm following early surgery of ruptured intracranial aneurysms.Twenty-four patients (80%) of them showed significant improvement in neurological function. Posttreatment angiography was carried out in seventeen patients and proved a resolution of arterial spasm in sixteen of these patients. In a few patients, CT scan taken after the treatment, demonstrated disappearance of low density area suggestive of ischemic lesion. The DIH should be commenced as early as possible especially within 24 hours from the onset of ischemic symptoms. Systolic blood pressure should be maintained adequately for sufficient periods of time. The mortality and morbidity of the patients complicated by symptomatic vasospasm could be improved by DIH combined with early operation for aneurysms.

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Dopamine infusion without hypertension was applied to the patient who had vasospasm after subarachnoid hemorrhage for the purpose of the improvement of the cerebral circulation.
Thirteen cases of the vasospasm were treated with the Dopamine therapy. Eleven cases of them were improved clinically, however, one of eleven cases showed an elevation of the blood pressure in spite of four falling cases. The early Dopamine therapy after the vasospasm may delive the early improvement of symptoms.

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Cerebral vasospasm is one of the most disastrous problems in the treatment of ruptured intracranial aneurysms. Cerebral ischemia often develops in patients with vasospasm following subarachnoid hemorrhage and patients suffer from varying degree of neurological deficits.
The purpose of this study is to evaluate effect of Hydergine and glyceol in the treatment of cerebral ischemia.
1) Experimental study
The effect of Hydergine and glyceol on the regional cerebral blood flow (rCBF) was evaluated in the area of ischemia produced in the brain of mongrel dogs by occlusion of the middle cerebral artery. The rCBF was measured with the hydrogen clearance method.
The rCBF significantly increased after intravenous infusion of Hydergine, 0.035mg/kg, and glyceol, 1g/kg.
2) Clinical study Three patients suffering from ischemic complications of vasospasm were treated with intravenous infusion of Hydergine, 3.6mg/day, and glyceol, 800ml/day. In two patients, neurological deficits completely disappeared within 2 weeks. In one patient, improvement of neurologic deficit was observed.
In conclusion, intravenous infusion of Hydergine and glyceol could be beneficial symptomatic vasospasm.

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We reported that the hyperdynamic therapy by the administration of a large amount of albumin was markedly effective for the treatment of symptomatic vasospasm with SAH caused by ruptured aneurysm. Based upon this results, we have attempted to use albumin prophylactically for the prevention of symptomatic vasospasm and obtained an excellent results.
In this report, we are reporting the results of this treatment, the amount and duration of albumin administration that we have used.
During the past two years, twenty five patients who belonged to the Group 3 CT classification of SAH reported by Fisher, in which have a possibility to develop 98% of symptomatic vasospasm, were the subject of this study. Eighteen patients out of 25 underwent an early operation of clipping aneurysm with the evacuation of subarachnoid blood clot and cisternal drainage. In 7 patients out of 25, surgery was intensively delayed by various reasons. After the confirmative CT scan for the diagnosis of SAH in Group 3, albumin 1-2 gm/kg/day were administered venously for 7-14 days in those 25 cases for the prevention of symptomatic vasospasm. Only three patients (16.7%) out of 18 who underwent early operation developed sympathetic vasospasm. Among seven patients whose operations were intentionally delayed, three patients (42.8%) developed symptomatic vasospasm.
Thus, the overall results were only 6 patients (24%) out of 25 developed symptomatic vasospasm. This was a very low incidence of symptomatic vasospasm compared with that of Fisher's report (98%). Analysis of the amount of albumin administration revealed that 1.0±0.3gm/kg/day in symptomatic vasospasm patients, and 1.25±0.3gm/kg/day in non-symptomatic patients. There was a statistically significant difference among those two groups. Five patients out of 6 in symptomatic vasospasm group did developed the neurological manifestations during the gradual decreasing period of albumin administration, 4-9 days after the beginning of this treatment with initial amount of 1.0 gm/kg/day of albumin administration.
It can be speculated that it may be possible to decrease the incidence of symptomatic vasospasm by the adequate amount of albumin administration even in the state of severe SAH during the waiting time for the surgery of the ruptured aneurysm. Moreover the symptomatic vasospasm may be able to be prevented, if the early operation of the clipping of aneurysm were performed with the extensive evacuation of subarachnoid blood clot and cisternal drainage followed by the postoperative hyperdynamic therapy using adequate amount of albumin administration.

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Although hemorrhagic infarction has been reported in many publications, little has been known about its occurrence following cerebral vasospasm. The authors have experienced 6 cases of hemorrhagic infarction after vasospasm, 3 cases which had received induced hypertension therapy for the improvement of the cerebral ischemia. In this study we presented the clinical characteristics and significances of the hemorrhagic infarction with special emphasis to its prevention.
Among 100 patients suffering from subarachnoid hemorrhage who admitted to the Kyoto University hospital from January 1980 to December 1981, 33 cases (33%) presented symptomatic vasospasm and were analized in this study. Dopamine-or isoproterenol-induced hypertension therapy was performed in 14 cases out of 33. Six cases developed insidious onset of consciousness disturbance 17.0±2.9 days after subarachnoid hemorrhage and 8.5±3.3 days after the onset of vasospasm. Computed Tomography revealed subcortical high density areas surrounded by low density areas. Multiple lesions were noted in 4 cases. Although mild or moderate degree of aggravation in consciousness was observed in all of 6 cases after the hemorrhagic infarction, none died of it. Systemic blood pressure was documented to increase concomitantly with the occurrence of hemorrhagic infarction in 3 cases, two of which had been treated with induced hypertension therapy. Blood pressure was found to increase by an averaged value of 24%after the completion of induced hypertension in 7 cases out of 14, although its etiology could not be clarified.
Clinical characteristics of the hemorrhagic infarction are considered to be as follows: it is likely to occur in aged patients with ruptured aneurysms located in the area of the anterior cerebral artery whose systemic blood pressure increase after the improvement of vasospasm.
The hemorrhagic infarction is supposed to attribute to relaxation of spastic arterial wall, which is analogous to the recanalization phenomenon of embolic occlusion.
In conclusion it is very important for the prevention of the hemorrhagic infarction following vasospasm to manage the systemic arterial pressure not only during induced hypertension therapy but also within a week after that.

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Raising blood pressure is often recommended as a form of initial treatment in cases of cerebral ischemia following vasospasm, but sometimes the effect of increased perfusion pressure may further deteriorate brain damage by increasing cerebral edema or producing hemorrhagic infarction.
Ninety-nine acute cases of ruptured cerebral aneurysms were analysed in this report in order to investigate whether development of these complications of induced hypertension could be predicted from the data obtained by clinical observations.
Forty six cases showed ischemic symptoms of delayed onset, and 31 cases were treated by induced hypertension using dopamine for average of 3.6 days. Seven cases out of 31 showed progressive enlargement of low density areas in CT and one of them developed hemorrhagic infarction. None of the clinical parameters in these cases, such as age, level of blood pressure, neurological condition or the interval between SAH and onset of ischemic symptoms etc., were significantly different from the other uncomplicated cases.
It was concluded that more parameters concerning hemodynamic aspects should be required for prediction of these complications of induced hypertension.

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Delayed cerebral vasospasm is an important determinant of the clinical outcome after subarachnoid hemorrhage. We have reported the fact that the arteries in the stage of delayed vasospasm shows not only the organic change of the vascular wall but also they have various degree of thrombi in the lumen. These thrombus supposed to be responsible to the development of clinical symptoms caused by vasospasm in addition to the stenosis of vascular lumen. In this respect, we expect MDS (dextran sulfate) should play effective role in diminishing the clinical aggaravation due to delayed vasospasm. The prognosis of the SAH patients treated by MDS became better compared to the previous non-treated cases. In the highly predicting cases of symptomatic angiospasm, MDS regimen is the choice immediately after neck clipping of aneurysm. If this regimen is combined with plasma expander therapy or induced hypertension therapy, mortality will turn better.

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Cerebral vasospasm has been considered to be one of the important factors which affect the eventual outcome of patients undergoing operation for ruptured aneurysms. The follow-up results of operation of 62 cases with ruptured aneurysm clearly showed that the presence of vasospasm unfavorably influenced the surgical outcome. Among 35 cases with spasm, only 5 patients had an excellent result and 14 good, while all 27 patients without spasm showed excellent (18) or good (9) result. Spasm was observed in 16 (76.2%) of 21 patients undergoing early operation (within 72 hours after hemorrhage), while it was observed in 19 (46.3%) of 41 patients undergoing late operation (8th day or later after hemorrhage). Therefore, the outcome was better in the later operation group. However, among the cases with spasm, there was no significant difference in the eventual outcome between the early and late operation groups. In 18 patients calcium antagonist YC-93 (nicardipine hydrochloride) was intravenously administered during pre- and postoperative periods from the day of admission. YC-93 did not prevent or inhibit the development of vasospasm, but the surgical outcome was better in the group with YC-93 than without it.
The present data showed that the presence of cerebral vasospasm unfavorably influence the outcome of operation for ruptured aneurysm, and that YC-93 did not inhibit vasospasm, but the surgical outcome was better in the group with YC-93.

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Four cases with symptomatic vasospasm which occurred after early operation of aneurysm, were treated by oxygenation at high pressure (OHP).
The subjects were limited to the cases
1) who underwent clipping of aneurysm within one week after onset of subarachnoid hemorrhage.
2) whose consciousness level was judged to have aggravated undoubtedly by vasospasm.
3) whose consciousness before aggravation was alert or nearly alert.
Results
1) Three cases who was started OHP before falling of consciousness level down to semicoma, obviously recovered.
2) One case who was started OHP after semicomatous stage lasting for 4 days, didn't recover and eventually died.
3) Four other cases who were not treated by OHP didn't recover and finally died.
4) The results indicate that OHP is beneficial as a treatment of cerebral ischemia produced by vasospasm, and also indicate that OHP should be started at the early stage of symptomatic vasospasm.

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From 1976 to 1981, 131 cases with the ruptured intracranial aneurysm were treated and data from these patients, such as age, aneurysmal location, preoperative clinical grading, timing of operation and postoperative ADL, were stored in computer and used for analysis. The analysis showed that postoperative ADL was strongly correlated with the preoperative grading and timing of operation.
Recently ruptured aneurysmal patients were treated with Y-9179, brain protective agent, postoperatively. Those cases were also reported and discussed its usefulness.

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Until an ultimate therapy for preventing cerebral vasospasm (VS) following rupture of intracranial aneurysm is established, investigative efforts should also be directed towards protection of the brain from ischemic damage caused by VS. Based on this view, a double-blind clinical trial of the cerebral protective agent, Nizofenone (Y-9179), was carried out.
Under the control of the central registry, only subjects having episode of SAH following rupture of aneurysm within 9 days prior to hospitalization were admitted to the study. Patients allocated to treatment received 10 mg of Nizofenone intravenously three times a day for five days, while those to placebo received the same amount of 5% glucose in the identical manner. As a rule, administration of the drug was started as early as possible prior to development of VS. Outcomes of patients were evaluated one month after the drug administration according to their functional capacities.
The study was terminated when subjects accumulated up to 100 cases. Having excluded ten cases of troubled operation or complications not related to SAH, 42 cases were assigned to Nizofenone and 48 cases to placebo. As to the distribution of the baseline variables, there were no statistically significant differences between two groups. Twenty-five out of 42 cases of Nizofenone (59.5%) and 29 out of 48 cases of placebo (60.4%) developed VS. Remarkable difference was not found between the two groups in the outcome of patients who did not develop VS in the course of illness. In patients who developed VS, however, better outcomes were achieved in the Nizofenone group than the placebo with a statistical significance (Mann-Whitney U-test, p<0.05).
The present results will facilitate clinical use of Nizofenone for alleviating delayed ischemic deficits following SAH, although the incidence of VS itself was not decreased by the use of it.

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Adenosine triphosphate (ATP) was used in 15 cases of ruptured intracranial aneurysm soon after the aneurysm was clipped in order to reduce the vasospasm. ATP was given in 40mg at first, then maintained in 100mg daily for 4 days to 22 days by continuous intravenous injection. In other 15 operative cases ATP was not used as a control. The frequency and the quantity of vasospasm was studied correlated with CAG findings, postoperative courses and CT findings. In ATP group the vasospasm was less frequent, the degree of vasospasm was mild and the postoperative course was more favorable in spite of the severe subarachnoid hemorrhage in CT finding in comparison with non-ATP group. The continuous administration of ATP will have good effect when ATP is used in addition to the conventional treatment for cerebral vasospasm after subarachnoid hemorrhage.

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