Effects of the Ca++-permeable nonselective cation channel blocker LOE 908 on subarachnoid hemorrhage—induced vasospasm in the basilar artery in rabbits

2003 ◽  
Vol 98 (3) ◽  
pp. 561-564 ◽  
Author(s):  
Yoshifumi Kawanabe ◽  
Tomoh Masaki ◽  
Nobuo Hashimoto
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intravenous Administration ◽  
Basilar Artery ◽  
Channel Blocker ◽  
Autologous Blood ◽  
Content Type ◽  
Dependent Part ◽  
Before And After ◽  
Fine Print

Object. The Ca++ influx into vascular smooth-muscle cells (VSMCs) plays a fundamental role in the development and chronic effects of vasospasm after subarachnoid hemorrhage (SAH). The Ca++-permeable nonselective cation channels (NSCCs) are activated by several endothelium-derived constricting factors such as endothelin 1 (ET-1) and thromboxane A2. Moreover, the receptor-operated Ca++ channel blocker LOE 908 inhibits ET-1—induced extracellular Ca++ influx via NSCCs in the VSMCs of the basilar artery (BA) and the NSCC-dependent part of ET-1—induced vasoconstriction of BA rings. The purpose of the present study was to evaluate the in vivo role of LOE 908 on SAH-induced vasospasm. Methods. Forty-two Japanese white rabbits were assigned to seven groups. Treatment groups consisted of the following: 1) control rabbits without SAH that received a cisternal injection of saline; 2) rabbits with SAH that were subjected to the intravenous administration of saline; 3 through 6) rabbits with SAH that underwent the intravenous administration of 0.01, 0.1, 1, or 10 mg/kg LOE 908, respectively; and 7) rabbits without SAH that underwent the intravenous administration of 10 mg/kg LOE 908. Autologous blood was injected into the cisterna magna. The caliber of the BA was measured on angiographic studies before and after the cisternal injection of autologous blood. The intravenous injection of LOE 908 inhibited the magnitude of an SAH-induced vasosapsm. In addition, the concentration of LOE 908 required to relax vasospasm (1 mg/kg) correlated with that required to block Ca++ influx into VSMCs. Conclusions. The Ca++ channel blocker LOE 908 may inhibit the magnitude of an SAH-induced vasospasm by blocking the influx of Ca++ through NSCCs in rabbit BAs. Blocking the NSCCs may represent a new treatment for cerebral vasospasm after SAH.

Role of ferrous iron chelator 2,2′-dipyridyl in preventing delayed vasospasm in a primate model of subarachnoid hemorrhage

1998 ◽  
Vol 88 (2) ◽  
pp. 298-303 ◽  
Author(s):  
Laura L. Horky ◽  
Ryszard M. Pluta ◽  
Robert J. Boock ◽  
Edward H. Oldfield
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Blood Clot ◽  
Autologous Blood ◽  
Iron Chelator ◽  
Preventive Therapy ◽  
Control Group ◽  
Primate Model ◽  
Content Type ◽  
Fine Print

Object. Oxyhemoglobin (HbO2) causes vasospasm after subarachnoid hemorrhage (SAH). The most likely spasmogenic component of HbO2 is iron. Various iron chelators, such as deferoxamine, have prevented vasospasm in vivo with limited success. However, only chelators of iron in the ferric state have been studied in animal models of vasospasm after SAH. Because free radical formation requires the ferrous (Fe++) moiety and Fe++ is a potent binder of the vasodilator nitric oxide, the authors hypothesized that iron in the ferrous state causes vasospasm and that chelators of Fe++, such as 2,2′-dipyridyl, may prevent vasospasm. This study was undertaken to investigate the influence of 2,2′-dipyridyl on vasospasm after induction of SAH in a primate model. Methods. Twelve cynomolgus monkeys were randomly divided into two groups and then both groups underwent placement of an arterial autologous blood clot in the subarachnoid space around the right middle cerebral artery (MCA). The five animals in the control group received intravenously administered saline and the seven treated animals received intravenously administered chelator (2,2′-dipyridyl) for 14 days. Sequential arteriography for assessment of MCA diameter was performed before and on the 7th day after SAH. Conclusions. Prevention of cerebral vasospasm by means of treatment with continuous intravenous administration of 2,2′-dipyridyl is reported in a primate model of SAH. This result provides insight into the possible mechanism of delayed vasospasm after aneurysmal SAH and provides a potential preventive therapy for it.

Prevention of cerebrovasospasm following subarachnoid hemorrhage in rabbits by the platelet-activating factor antagonist, E5880

1996 ◽  
Vol 84 (5) ◽  
pp. 826-830 ◽  
Author(s):  
Yutaka Hirashima ◽  
Shunro Endo ◽  
Ryoko Kato ◽  
Akira Takaku
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intravenous Administration ◽  
Basilar Artery ◽  
Platelet Activating Factor ◽  
Control Group ◽  
Distilled Water ◽  
Dependent Manner ◽  
Content Type ◽  
Arterial Blood ◽  
Fine Print

✓ Recently, an important role of platelet-activating factor (PAF), an inflammation mediator, has been demonstrated in the genesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). In the current study, the authors examined whether intravenous administration of the novel PAF antagonist, E5880, can prevent vasospasm following SAH in rabbits. A vasospasm model was produced in three groups of rabbits using two subarachnoid injections of autologous arterial blood, followed by intravenous administration of distilled water (control), a low dose of E5880 (0.1 mg/kg in distilled water), or a high dose of E5880 (0.5 mg/kg in distilled water). Neurological deterioration was largely prevented in the rabbits that received E5880. Basilar artery constriction was also reduced by both doses of E5880. Histological examination at autopsy predominantly showed ischemic changes in the brain. Animals in each E5880-treated group exhibited ischemic changes less frequently than those in the control group. Plasma thromboxane B2 concentrations were reduced in rabbits treated with E5880. Platelet-activating factor was immunolocalized in the intima and media of the basilar artery in the control group. The PAF immunoreactivity demonstrated in the basilar artery was decreased in the E5880 groups in a dose-dependent manner. Thus, this study provides evidence that PAF may play a role in the pathogenesis of vasospasm after SAH and that intravenous administration of E5880 is a promising approach in preventing vasospasm.

scholarly journals Application of the 1-µsec pulsed-dye laser to the treatment of experimental cerebral vasospasm

1991 ◽  
Vol 75 (2) ◽  
pp. 271-276 ◽  
Author(s):  
Atsushi Teramura ◽  
Robert Macfarlane ◽  
Christopher J. Owen ◽  
Ralph de la Torre ◽  
Kenton W. Gregory ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Laser Energy ◽  
Autologous Blood ◽  
Preliminary Investigation ◽  
Dye Laser ◽  
Pulsed Dye Laser ◽  
Content Type

✓ Laser energy of 480 nm was applied in 1-µsec pulses varying between 2.2 and 10 mJ to in vitro and in vivo models of cerebral vasospasm. First, the pulsed-dye laser was applied intravascularly via a 320-µm fiber to basilar artery segments from six dogs. The segments were mounted in a vessel-perfusion apparatus and constricted to, on average, 70% of resting diameter by superfusion with dog hemolysate. Immediate increase in basilar artery diameter occurred to a mean of 83% of control. In a second model, the basilar artery was exposed transclivally in the rabbit. In three normal animals, superfusion of the artery with rabbit hemolysate resulted in a reduction of mean vessel diameter to 81% of control. Following extravascular application of the laser, vessels returned to an average of 106% of the resting state. In six rabbits, the basilar artery was constricted by two intracisternal injections of autologous blood, 3 days apart. Two to 4 days after the second injection, the basilar artery was exposed. Extravascular laser treatment from a quartz fiber placed perpendicular to the vessel adventitia resulted in an immediate 53% average increase in caliber to an estimated 107% of control. No reconstriction was observed over a period of up to 5 hours. Morphologically, damage to the arterial wall was slight. This preliminary investigation suggests that the 1-µsec pulsed-dye laser may be of benefit in the treatment of cerebral 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.

Significance of a small bulge on the basilar artery in patients with perimesencephalic nonaneurysmal subarachnoid hemorrhage

2003 ◽  
Vol 98 (2) ◽  
pp. 426-429 ◽  
Author(s):  
Yuji Matsumaru ◽  
Kiyoyuki Yanaka ◽  
Ai Muroi ◽  
Hiroaki Sato ◽  
Takao Kamezaki ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Three Dimensional ◽  
Distinct Type ◽  
Rotational Angiography ◽  
Bleeding Pattern ◽  
Content Type ◽  
Nonaneurysmal Subarachnoid Hemorrhage ◽  
Excellent Clinical Outcome ◽  
Fine Print

✓ Perimesencephalic nonaneurysmal subarachnoid hemorrhage (SAH) is a distinct type of hemorrhage with a characteristic bleeding pattern and an excellent clinical outcome. The cause of this benign form of SAH remains unknown. The authors report on two cases of perimesencephalic nonaneurysmal SAH in which a small bulge on the basilar artery (BA) was demonstrated on three-dimensional rotational angiography studies. Based on data from these cases, one may infer that the lesion on the BA is responsible for the SAH. The possible pathogenesis is discussed.

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.

The effect of a lipid hydroperoxide of arachidonic acid on the canine basilar artery

1981 ◽  
Vol 54 (3) ◽  
pp. 357-365 ◽  
Author(s):  
Tomio Sasaki ◽  
Susumu Wakai ◽  
Takao Asano ◽  
Takashi Watanabe ◽  
Takaaki Kirino ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Basilar Artery ◽  
Morphological Changes ◽  
Degenerative Change ◽  
Lipid Hydroperoxide ◽  
Second Phase ◽  
Electron Microscopic ◽  
Content Type ◽  
Fine Print

✓ The in vivo spasmogenic capacity of a lipid hydroperoxide (15-hydroperoxy arachidonic acid: 15-HPAA) was studied in a chronic experiment using the dog. The 15-HPAA was injected into the cisterna magna (0.2 or 2 mg emulsified in bovine serum albumin solution). The changes in diameter of the basilar artery were followed by angiography, and the morphological changes were studied by electron microscopy. The cisternal injection of 0.2 mg of 15-HPAA caused a mild constriction of the basilar artery which lasted about 7 hours. The cisternal injection of 2 mg of 15-HPAA caused a biphasic constriction, the initial phase of which was a moderate narrowing lasting about 10 hours. The second phase started on the 2nd or the 3rd day after injection. The intensity of the arterial narrowing was more pronounced in the second phase than in the first. The prolonged secondary constriction of the basilar artery continued until sacrifice on the 7th day after injection. Electron microscopic study revealed a marked degenerative change in the endothelium and myonecrotic changes in the tunica media. The prolonged arterial constriction in the second phase was invariably associated with remarkable degeneration of the endothelium. On the other hand, myonecrotic changes were limited to a small number of smooth-muscle cells. The results of the present study are consonant with the hypothesis that lipid peroxidation associated with lysis of the subarachnoid clot is involved in the genesis of chronic vasospasm in subarachnoid hemorrhage.

Reduced platelet aggregability and thromboxane release after rebleeding in patients with subarachnoid hemorrhage

1991 ◽  
Vol 74 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Seppo Juvela ◽  
Marrku Kaste
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Statistical Significance ◽  
Adenosine Diphosphate ◽  
Blood Samples ◽  
Content Type ◽  
Platelet Aggregability ◽  
Before And After ◽  
Fine Print

✓ Serial blood samples were obtained from 80 patients with subarachnoid hemorrhage (SAH) to study adenosine diphosphate-induced platelet aggregation and associated thromboxane B2 release. The goal of the investigation was to detect whether reduced platelet function is involved in rebleeds. Seventeen patients (21%) suffered a rebleed, six of those experiencing their first rebleed within 24 hours after SAH. Therefore, most platelet function studies were performed after rebleeds. Thromboxane release was lower in patients with rebleeds than in the others, both before and after rebleeding, although statistical significance was reached only in samples collected after rebleeds. Patients rebleeding within 24 hours after SAH had lower platelet aggregability (p = 0.037) than patients without a rebleed in the samples taken within 3 days after SAH. The results suggest that reduced platelet aggregability and thromboxane release are involved in rebleeds following primary SAH.

A true mycotic (Aspergillus) aneurysm leading to fatal subarachnoid hemorrhage in a patient with hereditary hemorrhagic telangiectasia

1971 ◽  
Vol 35 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Peter Davidson ◽  
David M. Robertson
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Artery Aneurysm ◽  
Content Type ◽  
Intracranial Involvement ◽  
Basilar Artery Aneurysm ◽  
Fine Print

✓ A mycotic basilar artery aneurysm, in which Aspergillus was identified histologically, was found to be the cause of a massive subarachnoid hemorrhage in a 75-year-old man who suffered from hereditary hemorrhagic telangiectasia; there was no evidence of intracranial involvement by the latter disorder.

CSF leukotriene C4 following subarachnoid hemorrhage

1988 ◽  
Vol 69 (4) ◽  
pp. 488-493 ◽  
Author(s):  
Pietro Paoletti ◽  
Paolo Gaetani ◽  
Guido Grignani ◽  
Lucia Pacchiarini ◽  
Vittorio Silvani ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Subarachnoid Hemorrhage ◽  
Arterial Spasm ◽  
Lipoxygenase Pathway ◽  
Content Type ◽  
Symptomatic Vasospasm ◽  
Csf Levels ◽  
Fine Print

✓ Leukotrienes derive from arachidonic acid metabolism via the lipoxygenase pathway and modulate several cellular events. In the central nervous system, leukotrienes are mainly synthesized in the gray matter and in vascular tissues. Their production is enhanced in ischemic conditions and in experimental subarachnoid hemorrhage (SAH). Previous studies have indicated the ability of the leukotrienes C4 and D4 to constrict arterial vessels in vivo and in vitro and have suggested their involvement in the pathogenesis of cerebral arterial spasm. In the present study, the authors measured lumbar and cisternal cerebrospinal fluid (CSF) levels of leukotriene C4 in 48 patients who had suffered aneurysmal SAH. In 12 of the cases, symptomatic and radiological spasm was evident. The mean lumbar CSF level of immunoreactive-like activity of leukotriene C4 (i-LTC4) was significantly higher (p < 0.005) than in control cases, while the cisternal CSF level was higher than the lumbar mean concentration (p < 0.005). Patients presenting with vasospasm had significantly higher levels of i-LTC4 compared to patients without symptomatic vasospasm. This is the first report concerning monitoring of i-LTC4 levels in the CSF after SAH. The results of this study suggest that: 1) metabolism of arachidonic acid via the lipoxygenase pathway is enhanced after SAH; 2) the higher cisternal CSF levels of i-LTC4 may be part of the biological response in the perianeurysmal subarachnoid cisterns after the hemorrhage; and 3) the higher CSF levels of i-LTC4 in patients presenting with vasospasm suggest that a relationship exists between this compound and arterial spasm and/or reflect the development of cerebral ischemic damage.

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