Prostaglandin metabolism in experimental cerebral vasospasm

1981 ◽  
Vol 55 (5) ◽  
pp. 779-785 ◽  
Author(s):  
Yukio Maeda ◽  
Eiichi Tani ◽  
Tsumoru Miyamoto
Keyword(s):  
Platelet Aggregation ◽  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Content Type ◽  
Arterial Blood ◽  
Intracisternal Injection ◽  
Blood Injection ◽  
Canine Basilar Artery ◽  
Layer Chromatography ◽  
Fine Print

✓ Experimental cerebral vasospasm was produced in the canine basilar artery by an intracisternal injection of fresh autogenous arterial blood, and prostaglandins generated in spastic and nonspastic arteries were assessed by thin-layer chromatography. Prostaglandins synthesized in normal arteries were 6-keto-prostaglandin (PG)F1α, PGF2α, PGE2, and PGD2; 6-keto-PGF1α was the most abundant prostaglandin. The study of platelet aggregation suggested that prostacyclin (PGI2)-like activity was manufactured by the normal basilar artery. At 5 minutes after the intracisternal blood injection, no significant changes were evident in syntheses of prostaglandins generated by spastic artery. However, PGE2 synthesis was significantly increased in spastic artery 2 days after the intracisternal blood injection, and 6-keto-PGF1α and PGF2α synthesis and PGE2 synthesis were significantly decreased and increased, respectively, in spastic artery 6 days after the intracisternal blood injection. No significant changes were found in syntheses of 6-keto-PGF1α, PGF2α, and PGE2 manufactured by nonspastic arteries at any stage. Formation of thromboxane B2 was not detected in normal, spastic, or nonspastic arteries.

Evaluation of prostaglandin biosynthetic activity in canine basilar artery following subarachnoid injection of blood

1981 ◽  
Vol 55 (5) ◽  
pp. 771-778 ◽  
Author(s):  
Tomio Sasaki ◽  
Sei-itsu Murota ◽  
Susumu Wakai ◽  
Takao Asano ◽  
Keiji Sano
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Cerebral Artery ◽  
Basilar Artery ◽  
Biosynthetic Activity ◽  
Content Type ◽  
Blood Injection ◽  
Canine Basilar Artery ◽  
Subarachnoid Blood ◽  
Fine Print

✓ Transformation of arachidonic acid into prostaglandins was investigated in the basilar artery by incubating sections of artery with carbon-14-labeled arachidonic acid. Thin-layer radiochromatography revealed that, in normal canine basilar arteries, 14C-arachidonic acid was transformed mainly to 6-ketoprostaglandin (PG)F1α, a spontaneous metabolite of prostacyclin (PGI2). Among other prostaglandins, only a small amount of PGF2α was detected, whereas PGD2, PGE2, and thromboxane B2 were not. Arteries removed on Days 3 and 8 after subarachnoid blood injection showed a prostaglandin synthesis profile similar to that in the normal cerebral artery. In borate-buffered saline (0.1M borate buffer, pH 9.0/0.15M NaCl = 1:9, vol/vol), canine basilar artery produced a PGI2-like substance that inhibited adenosine diphosphate (ADP)-induced platelet aggregation. Its anti-aggregatory activity was completely abolished by acidification. Aspirin likewise inhibited production of the anti-aggregatory substance. From these results, it was concluded that the anti-aggregatory activity was due solely to the production of PGI2 by the arterial specimen. Based on the above results, PGI2 biosynthetic activity in the cerebral artery exposed to subarachnoid blood injection was bioassayed by measuring the inhibitory activity of the incubation product upon ADP-induced platelet aggregation following incubation of the arteries in borate-buffered saline for 5 to 30 minutes at 20°C, using synthetic PGI2-Na as a standard. The synthetic activity of PGI2 in the artery exposed to subarachnoid blood injection had diminished remarkably by Days 3 and 8. This diminution of PGI2 synthesis in the cerebral artery may be involved in the pathogenesis of cerebral vasospasm.

Posttreatment with adenovirus-mediated gene transfer of calcitonin gene—related peptide to reverse cerebral vasospasm in dogs

2002 ◽  
Vol 97 (1) ◽  
pp. 136-142 ◽  
Author(s):  
Motoyoshi Satoh ◽  
Eddie Perkins ◽  
Hitoshi Kimura ◽  
Jiping Tang ◽  
Yi Chun ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Cerebral Vasospasm ◽  
Treated Group ◽  
Positive Staining ◽  
Cmv Promoter ◽  
Content Type ◽  
Related Peptide ◽  
Arterial Blood ◽  
Blood Injection ◽  
Fine Print

Object. Gene transfer to cerebral vessels is a promising new therapeutic approach for cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was undertaken to explore whether a delayed treatment with adenovirus encoding the prepro-calcitonin gene—related peptide (CGRP), 2 days after initial blood injection, reduces cerebral vasospasm in a double-hemorrhage model of severe vasospasm in dogs. Methods. In 20 dogs, arterial blood was injected into the cisterna magna on Days 0 and 2. Thirty minutes after the second blood injection, the animals received either adenovirus encoding the prepro-CGRP gene (AdCMVCGRP—treated group, eight dogs) or adenovirus encoding the β-galactosidase gene (AdCMVβgal—treated group, six dogs) under the cytomegalovirus (CMV) promoter. One group of dogs did not receive treatment and served as controls (control SAH group, six dogs). Angiography was performed on Days 0 and 7 to assess cerebral vasospasm. On Day 7 following angiography, the animals were killed and their brains were stained with X-gal to detect the distribution of gene expression. Cerebrospinal fluid (CSF) was also tested for CGRP immunoreactivity. Severe vasospasm was observed in control SAH dogs on Day 7, and the mean basilar artery (BA) diameter was 53.4 ± 5.5% of the value measured on Day 0. Treatment with AdCMVβgal did not alter vasospasm (the BA diameter was 55 ± 3.9% of that measured on Day 0). The leptomeninges and adventitia of the BAs of dogs treated using AdCMVβgal demonstrated positive staining with X-gal. High levels of CGRP were measured in CSF from dogs that received AdCMVCGRP. In the group treated with AdCMVCGRP, vasospasm was significantly reduced (the BA diameter was 78.2 ± 5.3% of that measured on Day 0, p < 0.05 compared with the control SAH group and the AdCMVβgal group). Conclusions. In a model of severe vasospasm in dogs, gene transfer of CGRP after injection of blood attenuated cerebral vasospasm after SAH.

Experimental assessment of phenoxybenzamine in cerebral vasospasm

1979 ◽  
Vol 50 (2) ◽  
pp. 158-163 ◽  
Author(s):  
Richard P. White ◽  
Shang-Po Huang ◽  
A. Ainsworth Hagen ◽  
James T. Robertson
Keyword(s):  
Cerebrospinal Fluid ◽  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Experimental Assessment ◽  
Content Type ◽  
Cisterna Magna ◽  
Normal Behavior ◽  
Intracisternal Injection ◽  
Original Observation ◽  
Fine Print

✓ The effect of phenoxybenzamine (PBZ) on cerebral vasospasm of the basilar artery induced by the injection of 2 ml of blood into the cisterna magna of dogs was assessed in chronic experiments. The presence of vasospasm was documented arteriographically. In one group of animals, 12 mg/kg of PBZ was given intravenously 2 hours before the intracisternal injection of blood to ascertain whether this drug would prevent the development of vasospasm for 24 hours. In another group of animals a 10−2M solution of PBZ was given intracisternally 15 minutes after vasospasm was produced, and again 24 hours afterward, to determine if the drug would reverse an existing spasm. These drug-treated animals were compared with controls which were treated with saline alone. The results indicate that the drug treatment was not statistically superior to saline in any of the groups studied. The finding that saline injected into the cisterna magna reversed the cerebral vasospasm illustrates the importance of this procedure in evaluating effectiveness of drugs and confirms the original observation that washing the cerebrospinal fluid with saline can terminate an experimentally induced vasospasm. Moreover, the fact that intracisternal injections of saline were more effective when given soon after the establishment of vasospasm than when injected 24 hours afterward supports the conclusion of others that the pathogenesis of cerebral vasospasm changes with time. The results also indicate that the presence of cerebral vasospasm in some animals did not prevent the return of normal behavior.

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.

Combined effect of L-arginine and superoxide dismutase on the spastic basilar artery after subarachnoid hemorrhage in dogs

1994 ◽  
Vol 80 (3) ◽  
pp. 476-483 ◽  
Author(s):  
Yasukazu Kajita ◽  
Yoshio Suzuki ◽  
Hirofumi Oyama ◽  
Toshihiko Tanazawa ◽  
Masakazu Takayasu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Superoxide Anion ◽  
Content Type ◽  
Vasodilator Effect ◽  
Intracisternal Injection ◽  
Dose Dependent ◽  
Fine Print

✓ To investigate the function of nitric oxide (a major endothelium-derived relaxing factor) in cerebral arteries after subarachnoid hemorrhage (SAH) in vivo, several nitric oxide-related substances were administered to dogs that had undergone double SAH. These included L-arginine (a substrate for the formation of nitric oxide), NG-monomethyl-L-arginine (L-NMMA, an analog of L-arginine that inhibits the formation of nitric oxide from L-arginine), and superoxide dismutase (SOD, which protects nitric oxide from oxidation by superoxide anion), which were given via intracisternal injection. The diameter of the basilar artery was assessed angiographically. In intact dogs, intracisternal bolus injections of L-arginine (1, 10, or 100 µmol) produced a dose-dependent increase in the internal diameter of the basilar artery; conversely, L-NMMA reduced the diameter of the basilar artery from baseline in a dose-dependent manner. On Days 4 and 7, after two intracisternal injections of autologous blood, L-arginine produced transient vasodilation of the spastic basilar artery, whereas L-NMMA produced no significant vasoconstriction. The vasodilator effect of L-arginine after SAH was stronger on Day 4 than on Day 7, but less than in intact dogs. Intracisternal injection of SOD, which caused no effect per se, enhanced the duration of the vasodilator effect of L-arginine on the basilar artery on Day 4 and both the magnitude and duration of that effect on Day 7. Thus, the basal release of nitric oxide was impaired after SAH, but the ability to synthesize nitric oxide in the vascular wall was not abolished. The finding that the simultaneous injection of SOD enhanced and prolonged the vasodilation induced by sufficient exogenous L-arginine suggests that the inactivation of nitric oxide by superoxide anion contributes to the development of vasospasm.

Calpain-calpastatin system of canine basilar artery in vasospasm

1993 ◽  
Vol 79 (4) ◽  
pp. 537-543 ◽  
Author(s):  
Ikuya Yamaura ◽  
Eiichi Tani ◽  
Takaomi C. Saido ◽  
Koichi Suzuki ◽  
Nobutaka Minami ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Early Stage ◽  
Local Application ◽  
Neutral Protease ◽  
Control Group ◽  
Calpain Activity ◽  
Fresh Blood ◽  
Content Type ◽  
Canine Basilar Artery ◽  
Fine Print

✓ Vasospasm was produced in the canine basilar artery by a two-hemorrhage method, while contraction was induced in the normal canine basilar artery by a local application of KCl or serotonin after transclival exposure. The control animals were injected with saline instead of fresh blood. The activation of μ-calpain, a Ca++-dependent neutral protease, in the basilar artery was studied by evaluating the conversion from its inactivated into its activated form on immunoblots. In addition, the activity of calpastatin, an intrinsic inhibitor of calpain, in the basilar artery was determined by assay. The majority of the μ-calpain was inactivated in the control group. In the spastic group, μ-calpain was generally activated markedly in the early stage of vasospasm and moderately thereafter. The contraction induced by KCl or serotonin application was classified into the early phasic and the later tonic stages; μ-calpain was usually activated in the phasic stage and inactivated in the tonic stage. Calpastatin activity was significantly decreased during vasospasm, whereas it was not significantly changed in KCl- or serotonin-induced contraction. The final activity of μ-calpain results from the balance of μ-calpain and calpastatin. This suggests that μ-calpain activity was enhanced continuously in the spastic group and transiently in the KCl or serotonin group, and that the continuous activation of μ-calpain during vasospasm probably induced more proteolytic changes compared to those in the KCl or serotonin group.

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.

Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage

2000 ◽  
Vol 93 (3) ◽  
pp. 471-476 ◽  
Author(s):  
Yasushi Miyagi ◽  
Robin C. Carpenter ◽  
Toshinari Meguro ◽  
Andrew D. Parent ◽  
John H. Zhang
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Rho Kinase ◽  
Rt Pcr ◽  
Content Type ◽  
Blood Injection ◽  
Rho A ◽  
Rho Kinases ◽  
Fine Print

Object. Rho A, a small guanosine triphosphate—binding protein, and rho kinases have been suggested to play an important role in the agonist-induced myofilament Ca++ sensitization and cytoskeletal organization of smooth-muscle cells. To discover their possible roles in the prolonged contraction seen in cerebral vasospasm, the authors investigated the messenger (m)RNA expressions of rho A and rho-associated kinases α and β in the basilar artery (BA) of a rat double cisternal blood—injection model.Methods. An experimental subarachnoid hemorrhage (SAH) was achieved in rats by twice injecting autologous arterial blood into the cisterna magna of each animal. The mRNAs for rho A and rho-associated kinases α and β of the rat BA were analyzed using reverse transcription—polymerase chain reaction (RT-PCR). The cisternal blood injection induced a marked corrugation of elastic lamina and contraction of smooth-muscle cells observed with the aid of light and transmission electron microscopy in the rat BA on Days 3, 5, and 7. Results of the RT-PCR revealed that mRNAs for rho A and rho kinases α and β were expressed in the rat BA and that they were significantly upregulated and reached their peaks on Day 5.Conclusions. The mRNA upregulation of these proteins indicates that activation of rho A/rho kinase—related signal transduction pathways is involved in the development of long-lasting contraction of cerebral arteries after SAH.

Relative importance of hypertension compared with hypervolemia for increasing cerebral oxygenation in patients with cerebral vasospasm after subarachnoid hemorrhage

2005 ◽  
Vol 103 (6) ◽  
pp. 974-981 ◽  
Author(s):  
Andreas Raabe ◽  
Jügen Beck ◽  
Mike Keller ◽  
Hartmuth Vatter ◽  
Michael Zimmermann ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Tissue ◽  
Cerebral Vasospasm ◽  
Moderate Hypertension ◽  
Cerebral Oxygenation ◽  
Brain Oxygenation ◽  
Content Type ◽  
Arterial Blood ◽  
Hypertension Therapy ◽  
Fine Print

Object. Hypervolemia and hypertension therapy is routinely used for prophylaxis and treatment of symptomatic cerebral vasospasm at many institutions. Nevertheless, there is an ongoing debate about the preferred modality (hypervolemia, hypertension, or both), the degree of therapy (moderate or aggressive), and the risk or benefit of hypervolemia, moderate hypertension, and aggressive hypertension in patients following subarachnoid hemorrhage. Methods. Monitoring data and patient charts for 45 patients were retrospectively searched to identify periods of hypervolemia, moderate hypertension, or aggressive hypertension. Measurements of central venous pressure, fluid input, urine output, arterial blood pressure, intracranial pressure, and oxygen partial pressure (PO2) in the brain tissue were extracted from periods ranging from 1 hour to 24 hours. For these periods, the change in brain tissue PO2 and the incidence of complications were analyzed. During the 55 periods of moderate hypertension, an increase in brain tissue PO2 was found in 50 cases (90%), with complications occurring in three patients (8%). During the 25 periods of hypervolemia, an increase in brain oxygenation was found during three intervals (12%), with complications occurring in nine patients (53%). During the 10 periods of aggressive hypervolemic hypertension, an increase in brain oxygenation was found during six of the intervals (60%), with complications in five patients (50%). Conclusions. When hypervolemia treatment is applied as in this study, it may be associated with increased risks. Note, however, that further studies are needed to determine the role of this therapeutic modality in the care of patients with cerebral vasospasm. In poor-grade patients, moderate hypertension (cerebral perfusion pressure 80–120 mm Hg) in a normovolemic, hemodiluted patient is an effective method of improving cerebral oxygenation and is associated with a lower complication rate compared with hypervolemia or aggressive hypertension therapy.

scholarly journals Timing of ICAM-I Expression in a Canine Model of Post-Haemorrhagic Cerebral Vasospasm

2000 ◽  
Vol 6 (2) ◽  
pp. 95-106
Author(s):  
T. Abruzzo ◽  
G.G. Shengelaia ◽  
H.J. Cloft ◽  
G. Thaxton ◽  
P. Dudley ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Immunohistochemical Analysis ◽  
Canine Model ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Percent Reduction ◽  
Arterial Blood ◽  
Canine Basilar Artery ◽  
Histologic Changes

Temporal alterations in endothelial intercellular adhesion molecule I (ICAM-I) expression during the course of post-haemorrhagic cerebral vasospasm (PHCV) are correlated with angiographic and histologic changes in the canine basilar artery. Angiography was performed in six dogs to obtain baseline measurements of basilar artery diameter. In three dogs subarachnoid haemorrhage (SAH) was created by performing percutaneous puncture of the cisterna magna, and replacing 7 ml of cerebrospinal fluid with 7 ml of arterial blood. The remaining three dogs were used as controls. Daily angiography was performed on all dogs to determine the percent reduction in basilar artery diameter (%RBAD). One dog from each group was sacrificed after 24 hours. The remaining two dogs in each group were sacrificed after 48 hours. Each basilar artery was perfusion fixed and subjected to histologic, and immunohistochemical analysis. In the SAH group, the average %RBAD was 4 (+/- 3) at 24 hours, and 36 (+/- 1) at 48 hours. In the control group, the average %RBAD was — 1 (+/- 1) at 24 hours, and 0 (+/- 2) at 48 hours. Endothelial edema and endothelial expression of ICAM-I were found at 24 hours. At 48 hours post-SAH there was widespread endothelial desquamation, but no evidence of ICAM-I expression. In the control group, histology was normal and no ICAM-I expression was found at 24 or 48 hours. The results suggest that a brief window of therapeutic efficacy exists during the first postictal 24 hours where ICAM-I antagonists may be useful in suppressing the pathogenesis of PHCV.

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