| Spontaneous subarachnoid hemorrhage (SAH) is caused by brain aneurysm ruptured at 85%. Vasospasm (CVS) evoked by SAH act as a important factor aggravating patient's condition and causing disability and death. Digital subtraction arteriography (DSA) verified that 70% SAH lead to CVS. 30% SAH produced delayed ischemic neurologic deficits (DIND). CVS is called neurosurgical hiding killer. Up to now, any satisfactory theory has not been found in explaining CVS pathogenesis. The symptomatic SAH models were set up in this study. The change rules of endothelin (ET), nitric oxide (NO), calcitonin gene-related peptide (CGRP) in plasma and cerebrospinal fluid (CSF) and oxyhaemoglobin (OxyHb) in CSF were explored respectively in SAH models and patients with aneurysm ruptured by intravasocular embolism treatment. The correlation of them with CVS was studied also. The purpose was in order to investigate feasibility, reliability and efficacy about lumbar cistern constant drainage (LCCD) following SAH. Meanwhile, the diagnosis criteria of CVS were illuminated further. Symptomatic SAH models Set up:Two-hemorrhage method was applied to make symptomatic SAH models in this study. Major domestic canines were divided into two groups randomly. Canines' cisterna magna were punctured and fresh autologous blood was injected into under general anesthesia. The above was performed again after 48h. The models' food-intake and neurological disorder were observed and noted everyday. CT scanned SAH models' brains in order to understand blood injected dispersing state.Transcranial color Doppler(TCCD)was applied to measure mean blood flow velocity of SAH models' basal artery(VBA) regularly. Meantime, DSA was used to measure the caliber ratio of SAH models' basal artery. They acted as standards assessing CVS. This result showed the models' food-intake reduced to different degree after SAH and less after two-hemorrhage. The models' neurological disorder appeared to different extent and were more evident after two-hemorrhage. The models' food-intake and nerve function improved gradually after 10 days. CT scan showed canines' SAH. This meant SAH models were set up successfully in imaging. TCCD demonstrated that Vba of SAH models increased after 3 days, and faster on the 7th day and 10th day. Vba went down in two weeks gradually. It was remarkable difference the experimental group compared with control group(P<0.01). DSA showed that gentle CVS took up 16.7%, middle CVS 22.8%, and severe CVS 55.5%. The caliber ratio of SAH models' basal arteries showed light decrease on the 3rd day, and less on the 7th day and 10th day. This meant that BA vasospasm became more and more evident. It is of statistical significance that two groups compared with each other(P<0.05). The symptomatic CVS was more harmful to human clinically. Therefore, it was more important that symptomatic SAH model was established satisfactorily. Two-hemorrhage method may create more remarkable and lasting CVS and is often adopted to research CVS. The SAH models were ideal model because of it's good reproducibility and high morbidity of CVS.SAH models' symptoms and signs were observed and analyzed in this study. TCCD was used to survey SAH models' hemodynamics changes and judge CVS level. DSA assessed CVS from other different point of view in terms of caliber ratio of cerebral artery. The above may act as standards to diagnose and assess CVS. The purpose is to produce ideal SAH models and provide scientific basis to explore CVS after SAH pathogenesis, prevention and cure.? Molecular pathogenesis of subarachnoid hemorrhage and experimental study on lumbar cistern constant drainage:Canine SAH models in this study were divided into drainage group, lumbar puncture group and control group randomly. LCCD was given in drainage group for 14 days. About 100ml CSF was drained in SAH models everyday. Lumbar puncture group were punctured in lumbar cistern. About 10ml CSF was released everyday. Control group were only punctured in lumbar cistern for 1—2ml CSF sampleregularly. Radio-immunity test was applied to determine ET and CGRP concentration in plasma and CSF. Nitrate reductase method was used to determine NO concentration in plasma and CSF. OxyHb concentration was tested by colorimetry in CSF. TCCD was given to measure SAH models' VBa? and DSA was used to measure the caliber ratio of SAH models' BA regularly. CVS grades were estimated objectively.This experiment demonstrated ET concentration went up only lightly in plasma and CSF of drainage group. It dropped to normality basically after 10 days. However, ET concentration increased remarkably in plasma and CSF of lumbar puncture group and control group on the 3rd day. It went up to peak on the 7th day and lasted about two weeks. It was evident difference for drainage group to be compared with lumbar puncture and control group (/><0.01) . It showed that LCCD was able to eliminate ET in plasma and CSF. NO concentration went down only lightly in plasma and CSF of drainage group on the 3rd and 7th day. But NO concentration reduced great on the 3rd day and went down remarkably on the 7th day in plasma and CSF with lumbar puncture group and control group. It was evident difference that drainage groups was compared with lumbar puncture and control group (P<0.01). The test demonstrated that CGRP concentration decreased only a little in plasma and CSF with drainage groups on the 3rd day, and went to normality step by step. Nevertheless, CGRP concentration dropped on the 3rd day, went down evidently on the 7th day and went back unclearly in plasma and CSF with lumbar puncture group and control group. It was evident difference that drainage group was compared with lumbar puncture and control groups (P<0.05 ) . OxyHb went down remarkably in CSF with drainage group. However, OxyHb changed a little in CSF with lumbar puncture group and control group. It was evident difference that drainage group was compared with lumbar puncture and control group (P<0.01) .ET is endogenous vasoconstricting factor. NO is endogenous relaxing factor. CGRP is also endogenous relaxing factor. Experiment had proved that NO and CGRP hold strong antagonistic effect on ET. CVS turn up after SAH because that ET / NO balance was possibly to be broken down. It is essentially common recognition that ET, a important factor can cause CVS. The premise of CVS developed is cerebral vessels have to be soaked into hematocele of SAH. Cerebral vessels relaxing and constricting auto-regulation presented disorder. Blood vessels relaxing function decrease. To the contrary, constricting function increase. And then, CVS occur. Fe"1"1"in OxyHb perhaps may play a important role in CVS developing. Fe** is able to combine with NO and inhibit NO biological effects. High density ET in plasma and CSF can retrain NOs. NO contents reduce anomalously, and cerebral artery relaxing hypofunction occur. Because of CVS related to hematocele of SAH, hematocele in brain have to be removed as soon as possible. So, the morbidity of CVS decrease. It is the best time to get rid of hematocele before RBC lyse to give out OxyHb. Cleaved products of RBC in CSF such as OxyHb containing Fe""" may obstruct NO expanding vessels, and lead to CVS. Correlation analysis was applied in the research. It showed positive Correlation exist between ET and OxyHb, ET and VBa? OxyHb and Vba? NO and CGRP or caliber ratio of BA. Negative Correlation occurred between ET or OxyHb and caliber ratio of BA, NO or CGRP and ET or OxyHb. In this study, TCCD discovered very light CVS in drainage group. Moreover, it recovered on the whole normally after 10 days, But, severe CVS in lumbar puncture group and control group. VsAof SAH models increased after 3 days, remarkably quickened on 7th and lO^day. Then, VfiAof SAH models didn't improve after 10 days in the two groups. It showed CVS lasted too long time at serious level. DSA showed that caliber ratio of SAH models in drainage group was larger than that of SAH models in lumbar puncture group and control group. It represented the former CVS was lighter than the latter CVS. TCCD was able to assess CVS degree and judge CVS prognosis according to velocity of arteries flow, and trace to survey the whole range CVS changes. DSA was correlated to TCCD and evaluate CVS at a different angle. They verified LCCD following SAH was of feasibility, reliability and efficacy.This study proved that LCCD was able to promote to eliminate ET and OxyHb in CSF. NO and CGRP mediating vasodilation improved indirectly. ET in plasma was removed mostly through density ladder mechanism. It was to great extent to relieve CVS level and shorten CVS lasting period. From the experiment, NO and CGRP concentration in plasma and CSF didn't reduce, but been kept owing to drainage. The study proved that LCCD following SAH was of feasibility, reliability and efficacy.? Molecular pathogenesis of subarachnoid hemorrhage and clinical study on lumbar cistern constant drainage:In this research, 268 cases patients with aneurysm ruptured after endovascular treatment were given early LCCD as drainage group. TCCD was used to judge CVS level and prognosis. Other 86 cases patients with aneurysm ruptured afterendovascular treatment were merely given lumbar puncture as control group. The two groups were treated by coil embolism in 1—2h after hospital admission. Drainage group was carried out LCCD in 1—2h after coils embolism, 300ml CSF was drained everyday. About 30ml CSF was put out in control group by means of lumbar puncture everyday. Radio-immunity test was applied to determine ET and CGRP concentration in plasma and CSF. Nitrate reductase method was used to determine NO concentration in plasma and CSF. OxyHb concentration was tested by colorimetry in CSF. TCCD was given to measure VBa of patients, and DSA was used to measure the caliber ratio of patients' B A regularly. CVS degree was estimated objectively.CVS evaluation criteria were established according to clinical situation, TCCD and DSA results. Four grades was divided as follows: 0 grade, no CVS, no any clinical situation or headache with SAH, VMca< 120 cm/s, MCA caliber ratio 91 — 100%; I . light CVS, gentle headache, nausea and vomiting, VMca=120— 140cm/s, MCA caliber ratio 81—90%; TT. middle CVS, evident intracranial hypertension symptoms and signs, such as headache, nausea and vomiting, papilledema, or/ and drowsiness, consciousness gloom, light limbs motor disorder, Vmca=160—200 cm/s, MCA caliber ratio 71 — 80%; TTT. Severe CVS, superficial to middle coma or severe limbs motor disorder, VMca200—250cm/s, MCA caliber ratio 50—70%. IV. dying CVS deep coma, life signs changes , breath and circulation failure, VMca> 250cm/s , MCA caliber ratio <50%. This study demonstrated ET concentration went up only lightly in plasma and CSF with drainage group. It stepped up no apparently on the 7th and 10th. It dropped to normality basically after 10 days. However, ET concentration increased great in plasma and CSF of control group on the 3rd day. It went up to peak on the 7th and 10th day and lasted about two weeks. It was evident difference for drainage group to be compared with control group (P< 0.01) . It showed that LCCD was able to eliminated ET in plasma and CSF. NO concentration went down only lightly in plasma and CSF with drainage group on the 3rd day and back after the 10th day. But NO concentration reduced great on the 3rd day and went down remarkably on the 7* and 10th day in plasma and CSF of control group. It was significant difference that drainage groups compare with control group (<0.01). The research demonstrated that CGRP concentration decreased only a little in plasma and CSF with drainage group on the 3rd day, and went back normally step by step on theM* day. Nevertheless, CGRP concentration dropped very clearly on the 3rd day , went down to bottom evidently on the 7th and 10th day , and wentback unclearly in plasma and CSF control group. It was evident difference that drainage group was compared with control group (P<0.01) . OxyHb went down remarkably in CSF with drainage group. However, OxyHb changed a little in CSF with control group. It was evident difference that drainage group was compared with lumbar puncture and control group (P<0.0\) . In this study, TCCD discovered that Vmca went up lightly in drainage group after coil embolism. Moreover, it recovered on the whole normally after 10 days, But, VMca of control group appeared remarkably quick after 3 days, up to peak on 7th and lO^day. Then, It showed CVS with control group lasted too long time in serious level, However CVS with drainage group lasted very short period by light degree. It was significant difference that drainage group was compared with control group (P<0.01) . DSA showed that caliber ratio of drainage group was larger than that of control group. It represented the former CVS was lighter than the latter CVS. The two groups hold significant difference.It is possible that ET and OxyHb mediate strong CVS. They are thought as factors causing CVS. The action mechanism has been approved by most scholars. This study found that CVS morbidity was higher when ET and OxyHb concentration was thick. CVS morbidity was lower very clearly in drainage group due to ET and OxyHb removed in plasma and CSF. Control group was to the contrary. Especially, there was significant difference between ET or OxyHb of two groups on 7th and 10th day, It is 2—3 times different CVS between two groups. It showed that LCCD following SAH was of feasibility, reliability and efficacy. It likely profit to prevention and treat CVS.CVS following SAH often occurred after 2—3 days SAH, up to peak on the 6 to 7th day, restoring in 2to 3weeks. The times course of CVS was consistent with RBC split and OxyHb release process. Therefore, it is considered that OxyHb is one of main factors evoking CVS. RBC in CSF with SAH began to lyse after 16—32h, up to peak on the 7th and lasting presence. Cleaved products of RBC in CSF such as OxyHb containing Fe"1"1" was able to be combined with NO to obstruct NO expanding vessels. Hydrogen dioxide and superoxide free radical and single state oxide that RBC lysed to release are able to inhibit NO production and action , block up NO biological effects and lead to CVS finally. For this reason, haematocele after aneurysm ruptured have to be cleansed as soon as possible. It is the optimal time to get rid of hematocele before RBC solve to give out OxyHb. It is beneficial for NOand CGRP to exert biological actions. CVS is prohibited and lessened to great extent. TCCD and DSA proved that CVS morbidity of control group was 3 times or so than that of drainage group. It manifested LCCD promoted to eliminate ET and OxyHb in CSF. NO and CGRP mediating vasodilation was improved indirectly. It was to great extent to relieve CVS level and shorten CVS lasting period. Vasomotion auto-regulation balance renewed to restore through LCCD. It brought to light further that lumbar cistern constant drainage following SAH was of feasibility, reliability and efficacy.? Conclusion:CD Symptomatic SAH models was set up successfully. SAH models were analyzed and assessed objectively according to symptoms and signs, hemodynamics and caliber ratio of BA in this study.(2) CVS was caused by many of agents, related to anomalously high ET in plasma and CSF, and OxyHb in plasma , but also exceptionally lower NO and CGRP in plasma and CSF.(3) The research showed positive Correlation existed between ET and OxyHb, ET and VBa> OxyHb and VBa? NO and CGRP or caliber ratio of BA. Negative Correlation occurred between ET or OxyHb and caliber ratio of BA, NO or CGRP and ET or OxyHb.(4) The study manifested LCCD was able promote to eliminate anormally high ET and OxyHb concentration. NO and CGRP mediating vasodilation was improved indirectly. It was to great extent to relieve CVS level and shorten CVS lasting period. Vasomotion auto-regulation balance renewed to restore through LCCD. It brought to light that lumbar cistern constant drainage following SAH was of feasibility, reliability and efficacy.(5) CVS evaluation criteria were objectively illuminated further according to clinical situation, TCCD and DSA results.
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