Subarachnoid hemorrhage as a cause of an adaptive response in cerebral arteries

2000 ◽  
Vol 93 (3) ◽  
pp. 463-470 ◽  
Author(s):  
Marcus Stoodley ◽  
R. Loch Macdonald ◽  
Bryce Weir ◽  
Linda S. Marton ◽  
Lydia Johns ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Adaptive Response ◽  
Contractile Activity ◽  
Blood Clot ◽  
Cerebral Arteries ◽  
Content Type ◽  
Clot Removal ◽  
Basilar Arteries ◽  
Subarachnoid Blood ◽  
Fine Print

Object. It is not known whether the factors responsible for vasospasm after subarachnoid hemorrhage (SAH) cause the cerebral arteries to be narrowed independent of the subarachnoid blood clot or whether the continued presence of clot is required for the entire time of vasospasm. The authors undertook the present study to investigate this issue.Methods. To distinguish between these possibilities, bilateral SAH was induced in monkeys. The diameters of the monkeys' cerebral arteries were measured on angiograms obtained on Days 0 (the day of SAH), 1, 3, 5, 7, and 9. The subarachnoid blood clot was removed surgically on Day 1, 3, or 5 or, in control animals, was not removed until the animals were killed on Day 7 or 9. The concentrations of hemoglobins and adenosine triphosphate (ATP), substances believed to cause vasospasm, were measured in the removed clots and the contractile activity of the clots was measured in monkey basilar arteries in vitro. If the clot was removed 1 or 3 days after placement, vasospasm was significantly diminished 4 days after clot removal. Clot removal on Day 5 had no marked effect on vasospasm. There was a significant decrease over time in hemoglobin and ATP concentrations and in the contractile activity of the clots, although substantial hemoglobin and contractile activity was still present on Day 7.Conclusions. The authors infer from these results that vasospasm requires the presence of subarachnoid blood for at least 3 days, whereas by Day 5 vasospasm is less dependent on subarachnoid blood clot. Because the clot still contains substantial amounts of hemoglobin and contractile activity after 5 days, there may be an adaptive response in the cerebral arteries that allows them to relax in the presence of the stimulus that earlier caused contraction.

Prevention of cerebral vasospasm after SAH with a thromboxane synthetase inhibitor, OKY-1581

1982 ◽  
Vol 57 (1) ◽  
pp. 74-82 ◽  
Author(s):  
Tomio Sasaki ◽  
Susumu Wakai ◽  
Takao Asano ◽  
Kintomo Takakura ◽  
Keiji Sano
Keyword(s):  
Cerebral Vasospasm ◽  
Morphological Changes ◽  
Content Type ◽  
Synthetase Inhibitor ◽  
Thromboxane Synthetase Inhibitor ◽  
Thromboxane Synthetase ◽  
Basilar Arteries ◽  
Blood Injection ◽  
Subarachnoid Blood ◽  
Fine Print

✓ 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-methylacrylate)was used. Dogs received intravenous injections of 160 mg of OKY-1581 dissolved in 2 ml of physiological saline immediately after subarachnoid blood injection. Subsequently, the animals received continuous intravenous infusion of the drug at the rate of 4 gm/50 ml/24 hours until sacrifice 4 days after induction of SAH. Control dogs received subarachnoid blood injection without treatment with OKY-1581. Angiographic examination revealed that the late spasm was almost completely abolished by the treatment with OKY-1581. 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 the 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.

Antisense preproendothelin-oligoDNA therapy for vasospasm in a canine model of subarachnoid hemorrhage

1999 ◽  
Vol 90 (6) ◽  
pp. 1105-1114 ◽  
Author(s):  
Hiroki Ohkuma ◽  
Ian Parney ◽  
Joseph Megyesi ◽  
Aziz Ghahary ◽  
J. Max Findlay
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Dna Sequences ◽  
Combined Treatment ◽  
Canine Model ◽  
Clot Lysis ◽  
Therapeutic Effects ◽  
Causative Role ◽  
Content Type ◽  
Basilar Arteries ◽  
Fine Print

Object. The purpose of this study is twofold: 1) to test antisense genetic techniques used in the prevention of cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH), targeting the endothelin-1 (ET-1) gene; and 2) to determine if fibrinolysis of subarachnoid clot with recombinant tissue plasminogen activator (rtPA) could enhance the effect of antisense treatment.Methods. A total of 39 dogs were studied in this experiment. Placebo (six animals), rtPA (six animals), antisense preproET-1 oligodeoxynucleotide (ASOD; five animals), or rtPA plus ASOD (combined treatment; six animals) was injected into the cisterna magna 30 minutes after a second SAH was induced on the 2nd day of the experiment. The animals were observed until Day 7, when they underwent follow-up angiography and then were killed; their basilar arteries were removed for analysis. Control animals included in this study (two animals in each group) received placebo, rtPA, ASOD, or rtPA plus ASOD without induction of SAH, or rtPA with mismatched (nonsense) preproET-1 oligodeoxynucleotide following SAH. Six additional dogs were analyzed earlier following SAH.Dogs that received placebo developed severe vasospasm (51 ± 8% of baseline caliber). Administration of ASOD alone resulted in a mild reduction in vasospasm (64 ± 13% of baseline caliber) and rtPA alone resulted in a moderate reduction in vasospasm (81 ± 5% of baseline caliber); however, the combined therapy of rtPA plus ASOD almost completely prevented vasospasm (95 ± 6% of baseline caliber), which was significantly different from all other groups (p < 0.05). Morphological analysis of the basilar arteries yielded results similar to angiography with respect to vasospasm severity. The ASOD treatment combined with rtPA resulted in reduced ET-1 expression, as demonstrated by immunohistochemical staining of the arteries, and reduced preproET-1 levels on Day 4, as measured by reverse transcription—polymerase chain reaction. Nonsense DNA sequences had no effect on the vessels.Conclusions. Antisense preproET-1 oligodeoxynucleotide treatment, when combined with clot lysis caused by rtPA, reduced vasospasm in the canine model of SAH, and this effect appeared to be related to reduced ET-1 synthesis. The results of this experiment support a causative role for ET-1 early in the course of vasospasm development in dogs. The apparent additive therapeutic effects of antisense and fibrinolytic treatments could be due to clot lysis, which allows better delivery of oligodeoxynucleotides to arteries within the subarachnoid space.

Effect of early operation for ruptured aneurysms on prevention of delayed ischemic symptoms

1982 ◽  
Vol 57 (5) ◽  
pp. 622-628 ◽  
Author(s):  
Mamoru Taneda
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Reliable Method ◽  
Early Operation ◽  
Permanent Disability ◽  
Content Type ◽  
Giant Aneurysms ◽  
Ruptured Aneurysms ◽  
Blood Clots ◽  
Subarachnoid Blood ◽  
Fine Print

✓ The effect of removal of subarachnoid blood clots on the prevention of delayed ischemic deficit was evaluated in 239 consecutive patients with ruptured supratentorial non-giant aneurysms. All patients were hospitalized within 24 hours after subarachnoid hemorrhage (SAH) and were classified in Grades 1 to 4 according to the system of Hunt and Hess; classification was made immediately preoperatively in patients operated on within 48 hours after SAH, or 48 hours after SAH in patients for whom delayed operation was planned. Delayed ischemic deficit causing permanent disability or death occurred in 11 (25%) of 44 patients in whom surgery was planned to be delayed for 10 days or more, in 26 (27.7%) of 94 patients in whom the aneurysms were obliterated and blood clots adjacent to them were removed within 48 hours of SAH, and in 11 (10.9%) of 101 patients in whom the aneurysms were obliterated and extensive and aggressive removal of thick subarachnoid clots lying along the arteries (identified on computerized tomographic scan) was performed within 48 hours of SAH. Accordingly, early operation is an effective and reliable method to reduce the occurrence of severe delayed ischemic deficit only when subarachnoid blood clots are removed extensively and aggressively along the arteries within 48 hours of SAH.

Dose responses of cerebral arteries of the dog, rabbit, and man to human hemoglobin in vitro

1980 ◽  
Vol 53 (4) ◽  
pp. 486-490 ◽  
Author(s):  
Glyn R. Wellum ◽  
Thomas W. Irvine ◽  
Nicholas T. Zervas
Keyword(s):  
Cerebral Arteries ◽  
Postmortem Changes ◽  
Human Hemoglobin ◽  
Content Type ◽  
Weak Response ◽  
Basilar Arteries ◽  
Human Arteries ◽  
Dose Responses ◽  
Fine Print

✓ Dose responses in vitro of the basilar arteries of the dog, rabbit, and man to human hemoglobin are reported. For each species, the response occurred over a range of 10−9M to greater than 10−5M hemoglobin. When compared to a maximum serotonin contraction, the relative constriction induced by 10−5M hemoglobin was greater in the rabbit than in the dog, which in turn was greater than in man. The comparatively weak response of the human arteries is probably attributable to postmortem changes.

Subarachnoid hemorrhage—induced upregulation of the 5-HT1B receptor in cerebral arteries in rats

2003 ◽  
Vol 99 (1) ◽  
pp. 115-120 ◽  
Author(s):  
Jacob Hansen-Schwartz ◽  
Natalie Løvland Hoel ◽  
Cang-Bao Xu ◽  
Niels-Aage Svendgaard ◽  
Lars Edvinsson
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Real Time ◽  
Cerebral Vasospasm ◽  
Cerebral Arteries ◽  
Specific Treatment ◽  
Content Type ◽  
Sequence Of Events ◽  
Arterial Blood ◽  
Receptor Phenotype ◽  
Fine Print

Object. Cerebral vasospasm following subarachnoid hemorrhage (SAH) leads to reduced blood flow in the brain. Inspired by organ culture—induced changes in the receptor phenotype of cerebral arteries, the authors investigated possible changes in the 5-hydroxytryptamine (HT) receptor phenotype after experimental SAH. Methods. Experimental SAH was induced in rats by using an autologous prechiasmatic injection of arterial blood. Two days later, the middle cerebral artery (MCA), posterior communicating artery (PCoA), and basilar artery (BA) were harvested and examined functionally with the aid of a sensitive in vitro pharmacological method and molecularly by performing quantitative real-time reverse transcription—polymerase chain reaction (PCR). In the MCA and BA the 5-HT1B receptor was upregulated, as determined through both functional and molecular analysis. In response to selective 5-HT1 receptor agonists both the negative logarithm of the 50% effective concentration was increased (one log unit in the MCA and one half unit in the BA), as was the agonist's potency (increased by 50% in the MCA and doubled in the BA). In addition, the authors found an approximately fourfold increase in the number of copies of messenger RNA coding for the 5-HT1B receptor as determined by quantitative real-time PCR. In the PCoA no upregulation of the 5-HT1B receptor was observed. Conclusions. Changes in the receptor phenotype in favor of contractile receptors may well represent the end stage in a sequence of events leading from SAH to the actual development of cerebral vasospasm. Insight into the mechanism of upregulation may provide new targets for developing specific treatment against cerebral vasospasm.

Protein kinase C and diacylglycerol content in basilar arteries during experimental cerebral vasospasm in the dog

1995 ◽  
Vol 82 (5) ◽  
pp. 834-840 ◽  
Author(s):  
Masayuki Yokota ◽  
John W. Peterson ◽  
Marios C. Kaoutzanis ◽  
Kenta Yamakawa ◽  
Robert Sibilia ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cerebral Vasospasm ◽  
Blood Clot ◽  
Statistical Significance ◽  
Content Type ◽  
Control Value ◽  
Kinase C ◽  
Basilar Arteries ◽  
Subarachnoid Blood

✓ Sixteen dogs were entered into a study of the double subarachnoid hemorrhage (SAH) model of cerebral vasospasm. Six animals were sacrificed 72 hours after the first experimental SAH, and the remaining 10 animals were killed 72 hours after the second experimental SAH; ten additional animals served as controls. Basilar arteries were rapidly excised from the dogs and frozen. Multiple segments of the frozen arteries were analyzed independently for total protein and 1,2-diacylglycerol (DAG) content, which averaged 3.17 (± 0.27 standard error of the mean; SEM) pmol DAG/µg protein for all 25 arteries analyzed. A slight decreasing trend in DAG content relative to that of control vessels was found in vessels chronically constricted in situ by subarachnoid blood clot; however, this trend did not attain statistical significance. Two segments of the same vessels were assayed independently for protein kinase C (PKC) activity, which averaged 1.21 (± 0.08 SEM) pmol phosphate incorporation per minute per µg protein for all 24 arteries analyzed. A small decrease in PKC content was noted in vessels that experienced a single SAH; however, PKC returned to near control value in vessels subjected to double SAH. The ratio of particulate (membrane bound) to soluble PKC activity, an indicator of PKC translocation to the membrane and hence PKC activation, showed a small but statistically significant trend to increase with experimental SAH.

Responses to experimental subarachnoid hemorrhage in the spontaneously breathing primate

1980 ◽  
Vol 52 (3) ◽  
pp. 302-308 ◽  
Author(s):  
Charles Rothberg ◽  
Bryce Weir ◽  
Thomas Overton ◽  
Michael Grace
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Perfusion ◽  
Perfusion Pressure ◽  
Respiratory Pattern ◽  
Content Type ◽  
Cynomolgus Monkeys ◽  
Experimental Subarachnoid Hemorrhage ◽  
Subarachnoid Blood ◽  
Spontaneously Breathing ◽  
Fine Print

✓ The pathophysiological responses to experimental subarachnoid hemorrhage (SAH) were investigated in 20 spontaneously breathing cynomolgus monkeys. Four different volumes of fresh autogenous blood were used: 1.0, 1.33, 1.67, and 2.0 cc/kg. Five other animals had injection of 1.67 cc/kg of mock cerebrospinal fluid. Cerebral blood flow (CBF) was measured using the xenon-133 clearance technique. Respiratory rate and tidal volume were monitored by way of a Vertek pneumotach. The reduction of CBF after the SAH became more pronounced with increasing volumes of subarachnoid blood. The CBF remained reduced despite a return to normal of the cerebral perfusion pressure. Increasing SAH volumes were associated with greater abnormalities in the respiratory pattern, consisting of apnea and hyperventilation. These larger volumes were also associated with hypoxemia. Morbidity and mortality increased with increasing volumes of SAH, and are believed to be the result of a combination of decreased CBF, respiratory center disturbances, and pulmonary diffusion defects.

Intracranial mycotic aneurysms of extravascular origin

1972 ◽  
Vol 36 (5) ◽  
pp. 552-559 ◽  
Author(s):  
Charas Suwanwela ◽  
Nitaya Suwanwela ◽  
Srisakul Charuchinda ◽  
Chaturaporn Hongsaprabhas
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Carotid Artery ◽  
Internal Carotid Artery ◽  
Cavernous Sinus ◽  
Internal Carotid ◽  
Cerebral Arteries ◽  
Content Type ◽  
Mycotic Aneurysms ◽  
Fine Print

✓ Six patients with intracranial mycotic aneurysms of extravascular origin are reported. Four had aneurysms of the intracavernous portion of the internal carotid artery associated with thrombophlebitis of the cavernous sinus, and two had aneurysms of the cerebral arteries associated with meningitis. An aneurysm of this type may rupture, producing subarachnoid hemorrhage, or it may become thrombosed and decrease in size or spontaneously disappear. In some patients it may persist and develop calcification in the wall.

Contribution of Src tyrosine kinase to cerebral vasospasm after subarachnoid hemorrhage

2003 ◽  
Vol 99 (2) ◽  
pp. 383-390 ◽  
Author(s):  
Gen Kusaka ◽  
Hitoshi Kimura ◽  
Ikuyo Kusaka ◽  
Eddie Perkins ◽  
Anil Nanda ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Tyrosine Kinase ◽  
Cerebral Vasospasm ◽  
Mitogen Activated Protein Kinase ◽  
Src Tyrosine Kinase ◽  
Content Type ◽  
Upstream Regulator ◽  
Src Inhibitor ◽  
Basilar Arteries ◽  
Fine Print

Object. Mitogen-activated protein kinase (MAPK) has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether Src tyrosine kinase, an upstream regulator of MAPK, is involved in cerebral vasospasm. Methods. An established canine double-hemorrhage model was used. Twenty-four dogs were divided into four groups: control, vehicle-treated, Src inhibitor PP2—treated, and Src inhibitor damnacanthal—treated groups. Vehicle (dimethyl sulfoxide), PP2, or damnacanthal was injected daily into the cisterna magna of 18 dogs at 3 to 6 days after induction of SAH. Angiography was performed on Day 0 (the day on which the first blood injection was administered to induce SAH) and on Day 7. Western blot analysis of Src and MAPK activation in basilar arteries (BAs) collected on Day 7 post-SAH was performed. Severe vasospasm was observed in the BAs of vehicle-treated dogs. Mild vasospasm was observed in all dogs treated with Src inhibitors. Phosphorylated Src and MAPK were increased after SAH and activation of these kinases in the BAs was abolished by PP2 and damnacanthal. Conclusions. The tyrosine kinase Src is an important upstream regulator of MAPK, and inhibition of Src might offer a new therapy in the management of cerebral vasospasm.

Delayed CSF lavage for arteriographic and morphological vasospasm after experimental SAH

1985 ◽  
Vol 63 (6) ◽  
pp. 949-958 ◽  
Author(s):  
Eben Alexander ◽  
Peter McL. Black ◽  
Theodore M. Liszczak ◽  
Nicholas T. Zervas
Keyword(s):  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Blood Gases ◽  
Canine Model ◽  
Content Type ◽  
Clot Removal ◽  
Wilcoxon Rank Sum Test ◽  
Arterial Vasospasm ◽  
Chronic Vasospasm ◽  
Fine Print

✓ Irrigation of the subarachnoid space after aneurysmal subarachnoid hemorrhage (SAH) has been reported to alleviate subsequent arterial vasospasm. The authors have investigated the effect of lavage of the cerebrospinal fluid (CSF) space in the two-hemorrhage canine model of vasospasm. Twelve dogs had basilar cistern lavage with 120 cc of artificial CSF 24 hours after each of two SAH's, and 12 control dogs had two sequential SAH's without intervening lavage of clot. The amount of clot on the ventral brain stem was evaluated at sacrifice and was graded from 0 (no clot) to 4 (maximum clot) to assess the adequacy of clot removal. Dogs that had undergone lavage had a median grade of 1 (range Grade 0 to 2); control dogs had a median grade of 2 (range Grade 1 to 3.5, p < 0.001, Wilcoxon rank sum test), indicating significant reduction of gross clot by lavage. The neurological findings were graded from 0 to 5, based on meningismus, ataxia, paresis, and cranial nerve deficits. No significant differences in neurological grade were found on any day between the two groups. Satisfactory angiograms were obtained before and 7 days after hemorrhage and were controlled for blood pressure and blood gases; these showed significant spasm in both groups. There was a mean reduction (± standard deviation) of 21.6% ± 16.2% in basilar artery diameter in control dogs, compared to a 28.8% ± 15.1% reduction in dogs with lavage (difference not significant, t-test). There was a strong, but insignificant, trend toward reduction of endothelial desquamation in the basilar and middle cerebral arteries in dogs with lavage compared to control animals (p = 0.06). Corrugation and tearing of the elastica, thickened intima, intimal fibroplasia, vacuolization of the endothelial or smooth-muscle cells, and presence of blood cells in the adventitia occurred similarly in both groups. It appears that cisternal lavage 24 hours after hemorrhage in this model has no effect on the angiographic, neurological, or most morphological sequelae of SAH, in spite of evidence for removal of clot as seen at sacrifice. Any postulated interaction of clot and vessel resulting in chronic vasospasm must occur before this time. Evaluation of the effect of much earlier lavage (for instance, 1 hour after hemorrhage) may elucidate the point at which vasospasm is instigated after SAH, and help in determining what factors cause vasospasm.

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