Intimal proliferation of cerebral arteries after subarachnoid blood injection in pigs

1984 ◽  
Vol 61 (3) ◽  
pp. 494-500 ◽  
Author(s):  
Toshiki Takemae ◽  
P. Josephine Branson ◽  
John F. Alksne
Keyword(s):  
Cerebral Arteries ◽  
Arterial Injury ◽  
General Process ◽  
Content Type ◽  
Intimal Proliferation ◽  
Young Pigs ◽  
Experimental Subarachnoid Hemorrhage ◽  
Blood Injection ◽  
Medial Necrosis ◽  
Subarachnoid Blood

✓ A model of experimental subarachnoid hemorrhage in young pigs has been created using two subarachnoid blood injections. Cerebral arteries of the pig demonstrate intimal proliferation and medial necrosis 10 days after experimental blood injection; this appears to be a reaction to arterial injury. The similarity between the arterial reaction to subarachnoid blood and the general process of atherosclerosis is noted, and steps have been taken to insure that the vasculopathy described is truly a response to the injected blood. The authors conclude that the intimal proliferation observed between 1 and 2 weeks after experimental subarachnoid blood injection is an indicator of arterial injury and is, therefore, a good end point for further studies.

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.

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.

Ultrastructural evidence of arterial denervation following experimental subarachnoid hemorrhage

1986 ◽  
Vol 64 (2) ◽  
pp. 292-297 ◽  
Author(s):  
Thomas A. Duff ◽  
Grayson Scott ◽  
John A. Feilbach
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Prolonged Exposure ◽  
Cerebral Arteries ◽  
Content Type ◽  
Ultrastructural Evidence ◽  
Experimental Subarachnoid Hemorrhage ◽  
Catecholamine Histofluorescence ◽  
Increased Sensitivity ◽  
The Media ◽  
Adult Cats

✓ Loss of catecholamine histofluorescence, increased sensitivity to norepinephrine, and changes in alpha1 receptor binding have led to the proposal that denervation hypersensitivity may play a role in cerebrovascular spasm. Because the significance of these alterations has remained unclear, the present study was undertaken to determine whether there was direct ultrastructural evidence of arterial denervation following experimental subarachnoid hemorrhage. Under general anesthesia, adult cats were subjected to pre-pontine injection of blood or serum (5 to 7 ml) via a transclival approach. The animals were sacrificed 4, 7, or 10 days later and basilar artery segments were prepared for electron microscopy. Control vessels appeared normal, whereas those bathed in blood revealed unequivocal changes in neural and supporting elements, including: 1) disintegration of both clear- and dense-core vesicles; 2) fragmentation of varicosities; 3) loss of Schwann cell cytoplasm; and 4) axonal degeneration. These changes were most pronounced 7 days after instillation of blood, and correlated in time with maximal injury of the media and endothelium. Although the development of smooth-muscle hypersensitivity remains unsettled, this study indicates that prolonged exposure to blood can cause extensive denervation of cerebral arteries.

Adrenergic innervation of the cerebral blood vessels in the rabbit

1971 ◽  
Vol 35 (2) ◽  
pp. 148-154 ◽  
Author(s):  
S. John Peerless ◽  
M. Gazi Yasargil
Keyword(s):  
Basilar Artery ◽  
Cerebral Arteries ◽  
Adrenergic Innervation ◽  
Cerebral Blood Vessels ◽  
Content Type ◽  
Middle Cerebral Arteries ◽  
Transmitter Substance ◽  
Subarachnoid Blood ◽  
Adrenergic Fibers ◽  
Adrenergic Terminals

✓ The Hillarp technique of fluorescent staining of monoamines was used to examine the adrenergic fibers in the cerebral vessels of rabbit brains. These fibers were found to lie wholly within the deeper layers of the adventitia and not within muscle layers. Varicosities were interpreted as representing neural transmitter substance. The basilar artery had a sparse innervation; the anterior cerebral, carotid, and middle cerebral arteries were more richly supplied by adrenergic terminals, with the most dense innervation in the superficial vessels between 100 and 300 µ in diameter. Mild trauma to the basilar artery, as well as subarachnoid blood without trauma, caused the catecholamine reaction to disappear. A marked depletion of adrenergic fibers was also noted after administration of alpha methyl tyrosine and subjection of the animals to extremes of blood pressure.

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.

Cerebrovascular reactivity to noradrenaline and serotonin following experimental subarachnoid hemorrhage

1980 ◽  
Vol 53 (4) ◽  
pp. 480-485 ◽  
Author(s):  
Ramiro D. Lobato ◽  
Jesús Marín ◽  
Mercedes Salaices ◽  
Fernando Rivilla ◽  
Javier Burgos
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Time Course ◽  
Contractile Response ◽  
Cerebral Arteries ◽  
Cerebrovascular Reactivity ◽  
Content Type ◽  
Experimental Subarachnoid Hemorrhage ◽  
6 Hydroxydopamine ◽  
Chronic Cerebral Vasospasm ◽  
Supersensitivity To Noradrenaline

✓ This study analyzes the time course of the changes induced by subarachnoid hemorrhage (SAH) in the sensitivity of cat cerebral arteries to noradrenaline and serotonin. Cerebral arteries displayed a supersensitivity to these amines, which was most marked 3 days after the experiment and then gradually disappeared. The supersensitivity to serotonin was greater and longer than the response to noradrenaline. The increased in the vascular contractile response induced by SAH was similar to that seen after superior cervical ganglionectomy or intracisternal injections of 6-hydroxydopamine. It is suggested that supersensitivity to noradrenaline and serotonin induced by SAH may be involved in the production of chronic cerebral vasospasm.

Cerebrovascular responses to subarachnoid blood and serotonin in the monkey

1979 ◽  
Vol 50 (4) ◽  
pp. 441-448 ◽  
Author(s):  
Donald P. J. Boisvert ◽  
Bryce K. A. Weir ◽  
Thomas R. Overton ◽  
Rhoderick J. Reiffenstein ◽  
Michael G. A. Grace
Keyword(s):  
Cerebral Arteries ◽  
Blocking Agent ◽  
Post Injection ◽  
Content Type ◽  
Subarachnoid Injection ◽  
Artificial Cerebrospinal Fluid ◽  
Normal Monkey ◽  
Subarachnoid Blood ◽  
Fine Print

✓ Preliminary in vitro experiments were performed to determine the serum concentration of serotonin in the monkey, and the ability of cyproheptadine to block serotonin and serum-induced contractions in monkey cerebral arteries. Thirty-four cynomolgus monkeys were subsequently used to study changes in regional cerebral blood flow (CBF) obtained by the intracarotid 133Xe technique, and in the angiographic cerebral arterial caliber resulting from subarachnoid injection of artificial cerebrospinal fluid (CSF), blood, and serotonin. Five animals in each injection group were given 1.0 mg/kg intravenous cyproheptadine (a serotonin-blocking agent) during the post-injection period. Subarachnoid injection of artificial CSF produced no change in CBF or arterial caliber. Post-injection administration of cyproheptadine also had no effect on these parameters. A subarachnoid injection of fresh autogenous blood produced a significant but transient (less than 1 hour) decrease in CBF and moderate vasospasm, which lasted at least 3 hours. This vasospasm was essentially unaffected by intravenous cyproheptadine. The CBF and arterial caliber were unchanged following a subarachnoid injection of serotonin at concentrations (5 × 10−6M) present in normal monkey serum. In contrast, 5 × 10−6 M serotonin invariably produced near maximal contractions in the in vitro cerebral artery preparations. Higher (× 10) serotonin concentrations caused a transient CBF response similar to that obtained with blood. However, the cerebral vasospasm induced was of shorter duration than that obtained with blood. These results do not support a major role for serotonin in the production of post-subarachnoid hemorrhage vasospasm. Moreover, our data indicate that in vitro experiments do not reflect the ability of serotonin to constrict cerebral arteries in the intact animal.

Immunological reaction against the aging human subarachnoid erythrocyte

1989 ◽  
Vol 71 (5) ◽  
pp. 718-726 ◽  
Author(s):  
John W. Peterson ◽  
Byung-Duk Kwun ◽  
Atsushi Teramura ◽  
John D. Hackett ◽  
Jeffrey A. Morgan ◽  
...  
Keyword(s):  
Blood Clot ◽  
Cerebral Arteries ◽  
Cell Types ◽  
Complement Protein ◽  
Content Type ◽  
Artificial Cerebrospinal Fluid ◽  
Age Dependent ◽  
Subarachnoid Blood

✓ The role of the aging human erythrocyte in the mechanisms leading to cerebral vasospasm after subarachnoid hemorrhage was investigated using an in vitro model for the environment of the erythrocyte in a subarachnoid blood clot. It has long been suspected that, due to its potent vasoactivity, erythrocyte lysate provides the major vasoconstrictive input to cerebral arteries during vasospasm. Under the model conditions (incubation at 37°C in an artificial cerebrospinal fluid), however, the rate of spontaneous hemolysis was quite slow (about 1%/day), becoming only somewhat more rapid after 4 days' incubation. The rate of hemolysis of aging erythrocytes was dramatically increased (500- to 1000-fold) by the addition of plasma proteins, but only after the erythrocytes had aged 2 to 3 days, or more. The mechanism of age-dependent, plasma-induced hemolysis of originally autologous erythrocytes is shown to involve activation of the plasma complement protein pathway, analogous to the mechanisms of innate immunity which lead to lysis of nonautologous cell types and activate the inflammatory response.

Cerebral vasospasm evaluated by transcranial ultrasound correlated with clinical grade and CT-visualized subarachnoid hemorrhage

1986 ◽  
Vol 64 (4) ◽  
pp. 594-600 ◽  
Author(s):  
Rolf W. Seiler ◽  
Peter Grolimund ◽  
Rune Aaslid ◽  
Peter Huber ◽  
Helge Nornes
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Infarction ◽  
Cerebral Arteries ◽  
Clinical Status ◽  
Transcranial Doppler Sonography ◽  
Transcranial Ultrasound ◽  
Unaffected Side ◽  
Content Type ◽  
Middle Cerebral Arteries ◽  
Subarachnoid Blood

✓ In 39 patients with a proven subarachnoid hemorrhage (SAH), the clinical status, the amount of subarachnoid blood on a computerized tomography scan obtained within 5 days after SAH, and the flow velocities (FV's) in both middle cerebral arteries (MCA's) measured by transcranial Doppler sonography were recorded daily and correlated. All patients had pathological FV's over 80 cm/sec between Day 4 and Day 10 after SAH. The side of the ruptured aneurysm showed higher FV's than did the unaffected side in cases of laterally localized aneurysms. Increase in FV preceded clinical manifestation of ischemia. A steep early increase of FV's portended severe ischemia and impending infarction. Maximum FV's in the range of 120 to 140 cm/sec were not critical and in no case led to brain infarction. Maximum FV's over 200 cm/sec were associated with a tendency for ischemia, but the patients may remain clinically asymptomatic. In cases of no or only a little blood in the basal cisterns, mean FV's in both MCA's increased only moderately whereas, with thick clots of subarachnoid blood, there was a steeper and higher increase of mean FV's.

Barrier disruption in the major cerebral arteries following experimental subarachnoid hemorrhage

1985 ◽  
Vol 63 (3) ◽  
pp. 433-440 ◽  
Author(s):  
Tomio Sasaki ◽  
Neal F. Kassell ◽  
Masanori Yamashita ◽  
Shigeru Fujiwara ◽  
Mario Zuccarello
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Arterial Wall ◽  
Cerebral Arteries ◽  
Aneurysm Rupture ◽  
Post Contrast ◽  
Content Type ◽  
Sudden Rise ◽  
Branching Points ◽  
Experimental Subarachnoid Hemorrhage ◽  
Transient Elevation

✓ The effects of experimental subarachnoid hemorrhage (SAH) on the blood-arterial wall barrier in the major cerebral arteries were studied in 20 normotensive dogs. Horseradish peroxidase (HRP) was given intravenously before the animals were sacrificed to assess the integrity of the barrier. Transient elevation of intracranial pressure (ICP) produced by cisternal injection of saline solution resulted in HRP leakage at the branching points of the major cerebral arteries. Extensive disturbance of the blood-arterial wall barrier was consistently observed in the major cerebral arteries after SAH, with or without elevation of ICP. These results suggest that both subarachnoid clot and a sudden rise in the ICP are important factors causing the breakdown of the blood-arterial wall barrier, but that the effect of the clot is the most profound. Electron microscopy revealed that opening of the interendothelial junctions is one of the important mechanisms responsible for the HRP leakage in the major cerebral arteries following SAH. Disturbance of arterial permeability in the major cerebral arteries following SAH probably accounts for the abnormal post-contrast enhancement that occurs in patients who are prone to develop vasospasm following aneurysm rupture, and is probably involved in the pathogenesis of vasospasm.

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