Prolonged vasospasm produced by the breakdown products of erythrocytes

1977 ◽  
Vol 47 (3) ◽  
pp. 403-411 ◽  
Author(s):  
Kunihiko Osaka
Keyword(s):  
Cerebral Vasospasm ◽  
Arterial Wall ◽  
Platelet Rich Plasma ◽  
Prolonged Incubation ◽  
Content Type ◽  
Fresh Serum ◽  
Fresh State ◽  
Basilar Arteries ◽  
Fine Print

✓ The cause of cerebral vasospasm has been generally attributed to the vasoconstrictive substances released from platelets. The role of extravasated erythrocytes in vasospasm has never been well analyzed. To elucidate this point, the basilar arteries of cats were exposed and subjected to topical application of various blood fractions in their fresh state and after prolonged incubation for 1 to 7 days. Incubation was done to test stability of the vasoconstrictors. Severe vasospasm was induced by application of fresh and incubated fractions of lysed erythrocytes. Fresh, intact erythrocytes had no vasoactivity, but by incubation they lysed and gained vasoconstrictors. Vasospasm induced by lysed erythrocytes both in their fresh state and after prolonged incubation never relaxed, and tended to increase in severity during observation up to 24 hours. Fresh serum and platelet-rich plasma had vasoconstrictors, but they were lost after incubation. Apparently platelet-induced vasoconstriction is of short duration and contributes only to the early phase of vasospasm. Later, 12 to 24 hours after hemorrhage, iron pigments released by lysis of extravasated erythrocytes (oxyhemoglobin or methemoglobin) irritate the arterial wall and induce prolonged vasospasm. It is emphasized that the study of cerebral vasospasm should be focused on the role of the breakdown products of extravasated erythrocytes.

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.

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.

Neuropeptide Y in the primate model of subarachnoid hemorrhage

1992 ◽  
Vol 77 (3) ◽  
pp. 417-423 ◽  
Author(s):  
Ryszard M. Pluta ◽  
Anna Deka-Starosta ◽  
Alois Zauner ◽  
Jay K. Morgan ◽  
Karin M. Muraszko ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Neuropeptide Y ◽  
Cerebral Vasospasm ◽  
Primate Model ◽  
Content Type ◽  
Peripheral Plasma ◽  
Delayed Cerebral Vasospasm ◽  
Arterial Plasma ◽  
Fine Print

✓ The cause of cerebral vasospasm after subarachnoid hemorrhage (SAH) remains unknown. Recently, an association between the potent vasoconstricting peptide, neuropeptide Y, and delayed cerebral vasospasm after SAH has been postulated. This was based on the findings of increased neuropeptide Y levels in the cerebrospinal fluid (CSF) and plasma after SAH in animals and humans. For this study, the primate model of SAH was used to assess the possible role of neuropeptide Y in delayed vasospasm after SAH. Fifteen cynomolgus monkeys underwent placement of a clot of either whole blood or red blood cells in the subarachnoid space around the middle cerebral artery (MCA). Sequential arteriography for assessment of MCA diameter and sampling of blood and CSF for neuropeptide Y were performed: before SAH (Day 0); 7 days after SAH, when signs of delayed cerebral vasospasm peak in this model and in humans; 12 days after SAH; and 28 days after SAH. Subarachnoid hemorrhage did not evoke changes in CSF or plasma levels of neuropeptide Y. Nine monkeys had arteriographic evidence of vasospasm on Day 7, but no change in neuropeptide Y levels occurred in plasma or CSF. In addition, neuropeptide Y levels did not change, even after resolution of vasospasm on Day 12 or Day 28. Neuropeptide Y levels were substantially higher in CSF than in arterial plasma (p < 0.003 at each interval). No correlation was found between neuropeptide Y levels in CSF and in plasma. These results do not confirm a relationship between neuropeptide Y levels in the CSF or peripheral plasma and delayed cerebral vasospasm in SAH.

Natriuretic peptide system and endothelin in aneurysmal subarachnoid hemorrhage

1997 ◽  
Vol 87 (2) ◽  
pp. 275-280 ◽  
Author(s):  
Eelco F. M. Wijdicks ◽  
Wouter I. Schievink ◽  
John C. Burnett
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Natriuretic Peptide ◽  
Cerebral Vasospasm ◽  
Fluid Balance ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Content Type ◽  
Peptide System ◽  
Natriuretic Peptide System ◽  
Fine Print

✓ The natriuretic peptide system consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The system is implicated in the control of body fluid homeostasis, causes natriuresis and diuresis (ANP and BNP), and regulates vascular tone (CNP). A reciprocal relationship between ANP and endothelin (ET) has been suggested, and earlier studies have documented a possible role of ET in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The authors studied plasma ANP, BNP, CNP, and ET for 6 consecutive days in 13 patients with SAH by using radioimmunoassay. The median admission values for ANP were 31.5 pg/ml (range 16.8–323 pg/ml [normal 15 ± 7 pg/ml]); for BNP, 45.3 pg/ml (range 2.2–80.2 pg/ml [normal 12 ± 9 pg/ml]); for CNP, 7.7 pg/ml (range < 2–20 pg/ml [normal 5.2 ± 3 pg/ml]); and for ET, 11 pg/ml (range 6.5–25.1 pg/ml [normal 7.2 ± 4 pg/ml]). Additional increases (defined as > 100% increase on two consecutive measurements) were noted in ANP (11 patients), BNP (10 patients), and CNP (three patients), and resulted in a negative fluid balance in 10 of the 13 patients. The CNP increased in three of four patients with cerebral vasospasm and in one of nine patients without cerebral vasospasm (Fisher's exact test, p = 0.2). No major fluctuations in plasma ET were noted. In seven patients, the plasma ET level did not increase beyond 10 pg/ml during the days of measurement. In six patients, only an occasional sample showed an increase to a maximum of 25 pg/ml. Changes in BNP, ANP, and CNP were independent of each other. The authors conclude that both plasma ANP and BNP increase after SAH and often result in a negative fluid balance. Plasma ANP and BNP seem differentially regulated in the presence of SAH but not by the level of the plasma ET. The possible role of CNP as a regulatory response to cerebral vasospasm needs further exploration.

Acute subdural hematomas of arterial origin

1974 ◽  
Vol 41 (4) ◽  
pp. 435-439 ◽  
Author(s):  
Paul K. O'Brien ◽  
John W. Norris ◽  
Charles H. Tator
Keyword(s):  
Vessel Wall ◽  
Arterial Wall ◽  
Acute Subdural Hematoma ◽  
Subdural Space ◽  
Small Surface ◽  
Content Type ◽  
Subdural Hematomas ◽  
Arterial Bleeding ◽  
Fine Print

✓ Five cases of acute subdural hematoma associated with bleeding from cortical arteries are described. In the four cases in which the affected vessel was examined histologically, there was a defect in the arterial wall secondary to avulsion of a small surface twig, which had apparently been traversing the subdural space. The possible mechanisms for damage to the vessel wall and the role of this arterial bleeding in subdural hematomas are discussed.

The role of hemolysate in the facilitation of oxyhemoglobin-induced contraction in rabbit basilar arteries

1994 ◽  
Vol 81 (2) ◽  
pp. 261-266 ◽  
Author(s):  
Toshiki Aoki ◽  
Katsunobu Takenaka ◽  
Satoshi Suzuki ◽  
Neal F. Kassell ◽  
Oren Sagher ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Contractile Response ◽  
Weight Fraction ◽  
Low Molecular Weight ◽  
Equal Concentration ◽  
Content Type ◽  
Basilar Arteries ◽  
Fine Print

✓ The importance of factors within hemolysate in modulating oxyhemoglobin (oxyHb)-induced contraction was examined in an in vitro model of rabbit basilar arteries. When the basilar arteries were exposed to purified oxyHb alone, the contractile response observed was significantly weaker than that seen in arteries exposed to hemolysate containing an equal concentration of oxyHb. In order to delineate the nature of the factors within hemolysate that facilitate contraction, hemolysate was fractionated, and various components were tested individually for their ability to elicit this effect. A low-molecular-weight fraction of hemolysate, ranging from 0.5 to 2.0 kD, elicited only a mild contraction. However, when this fraction was combined with purified oxyHb, the contractile response was comparable in magnitude to that of unfractionated hemolysate. These studies confirm that purified oxyHb is capable of inducing contraction in vitro. The data also demonstrate that oxyHb elicits a significantly weaker contraction than does hemolysate. In addition, the results suggest that low-molecular-weight components in hemolysate (in the 0.5- to 2.0-kD range), while incapable of inducing a potent contraction alone, may act in concert with oxyHb to elicit the vasoconstriction seen following subarachnoid hemorrhage.

The role of hemoglobin in the etiology of cerebral vasospasm

1983 ◽  
Vol 59 (2) ◽  
pp. 231-236 ◽  
Author(s):  
David J. Boullin ◽  
Philip Tagari ◽  
George du Boulay ◽  
Victoria Aitken ◽  
J. Trevor Hughes
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Cerebral Angiography ◽  
Aneurysm Rupture ◽  
Neurological Deficits ◽  
Arterial Spasm ◽  
Content Type ◽  
Experimental Animals ◽  
Fine Print

✓ Oxyhemoglobin was injected intracisternally into three baboons, and methemoglobin into one baboon, in an attempt to mimic the prolonged cerebral arterial spasm sometimes seen after subarachnoid hemorrhage due to aneurysm rupture. Cerebral angiography was performed for up to 7 days after injection of hemoglobin, and the degree of vasospasm was estimated from the angiograms. Oxyhemoglobin caused slight arterial narrowing, which lasted for 3 days. Methemoglobin had no significant effects. Motor neurological deficits and histopathological signs, characteristic of prolonged cerebral vasospasm, were not observed. It was concluded that hemoglobin alone is not capable of causing the cerebral vasospasm syndrome in these experimental animals.

Possible role of the erythrocyte in causing prolonged cerebral vasospasm

1979 ◽  
Vol 51 (6) ◽  
pp. 773-778 ◽  
Author(s):  
Nobuyuki Ozaki ◽  
Sean Mullan
Keyword(s):  
Cerebral Vasospasm ◽  
Contractile Activity ◽  
Platelet Rich Plasma ◽  
Red Cells ◽  
Significant Activity ◽  
Sephadex Column ◽  
Content Type ◽  
Canine Basilar Artery

✓ Contractile activity of the various fractions of fresh and incubated blood was studied in vitro using the isolated canine basilar artery. Of the various fractions of fresh blood, significant contraction was induced by serum, but moderate contraction was induced by platelet-rich plasma and lysed red cells, while intact red cells and platelet-poor plasma had no significant activity. The contractions induced by serum and platelet-rich plasma were blocked by phenoxybenzamine, while those induced by lysed red cells were not. Whereas serum and platelet-rich plasma lost their contractile activity after 24 hours of incubation, lysed red cells retained activity up to 7 days after incubation. Biochemical analysis of the hemolysate by means of Sephadex column chromatography revealed that the contractile substance(s) possessed a molecular weight above 5000. These results suggest the possibility that the above substance(s) may play a role in prolonged cerebral vasospasm.

Cerebral artery spasm

1978 ◽  
Vol 48 (4) ◽  
pp. 515-525 ◽  
Author(s):  
J. Trevor Hughes ◽  
Pietro M. Schianchi
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Histological Examination ◽  
Cerebral Vasospasm ◽  
Arterial Wall ◽  
Arterial Occlusion ◽  
Intimal Thickening ◽  
Content Type ◽  
Small Arteries ◽  
Acute Changes ◽  
Fine Print

✓ From a larger series of autopsies with subarachnoid hemorrhage (SAH), 20 cases were selected for the known complication of cerebral vasospasm. Evidence for vasospasm was radiological and pathological in 17 cases and pathological alone in three. A systematic histological examination of the large arteries in places known formerly to have been in spasm showed that, in the 12 early cases (death before 3 weeks), there were relevant changes in all the layers of the arterial wall, the most significant being evidence of necrosis in the tunica media. In the eight late cases (death after 3 weeks), in addition to the sequelae of the earlier acute changes, there was marked concentric intimal thickening by subendothelial fibrosis, again located in the segments of arteries formerly in spasm. Changes were also found in the small arteries, capillaries, and veins, both in the early and late cases but these changes, although striking, were thought to be caused by the ischemia due to the vasospasm; similar changes were also seen in the control cases with ischemia from arterial occlusion.

Suramin-induced reversal of chronic cerebral vasospasm in experimental subarachnoid hemorrhage

2002 ◽  
Vol 97 (1) ◽  
pp. 129-135 ◽  
Author(s):  
Hitoshi Kimura ◽  
Toshinari Meguro ◽  
Ahmed Badr ◽  
John H. Zhang
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Tyrosine Kinase ◽  
Cerebral Vasospasm ◽  
Disulfonic Acid ◽  
Control Group ◽  
Content Type ◽  
Basilar Arteries ◽  
Blood Injection ◽  
The Mean ◽  
Fine Print

Object. The naphthylsulfonate derivative suramin is an inhibitor of growth factor receptors (receptor tyrosine kinases) and G protein—coupled P2Y receptors. Both types of these receptors are suspected of being involved in cerebral vasospasm after subarachnoid hemorrhage (SAH). In the current study, the authors examined the therapeutic effects of suramin and a selective P2X-receptor antagonist, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), in the reversal of vasospasm in an established canine double-hemorrhage model. Methods. Twenty-four dogs underwent double blood injection into the cisterna magna, with injections given on Days 0 and 2. The dogs were divided randomly into three groups (six animals in each group) to be treated from Days 2 through 6 with the vehicle dimethyl sulfoxide, suramin, or PPADS. An additional group of six dogs received double blood injection without any treatment and served as an SAH control group. The animals were killed on Day 7. Angiography was performed on Day 0 before blood injection and again on Day 7 before the animals were killed. After the death of the animals, the basilar arteries (BAs) were collected for morphological studies and determination of tyrosine kinase expression, and the bloody cerebrospinal fluid (CSF) produced by the hemorrhages was collected for measurement of oxyhemoglobin and adenosine triphosphate (ATP). In the SAH control group, the mean diameter of the BAs on Day 7 was 46.23 ± 6.32% of the value on Day 0 (which served as a reference of 100%). In the DMSO-treated group, the mean residual diameter of the BA was 47.77 ± 0.8% on Day 7 compared with the value on Day 0. Suramin, but not PPADS, increased the residual diameter to 74.02 ± 4.24% on Day 7. On Day 7 the level of ATP in the CSF was decreased and the level of oxyhemoglobin was increased, compared with values measured on Day 0. Suramin, but not PPADS, reduced tyrosine phosphorylation in the spastic BAs. Conclusions. By reducing tyrosine kinase activity, suramin may be useful in the treatment of cerebral vasospasm.

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