Histological studies of intracranial vessels in primates following transluminal angioplasty for vasospasm

1993 ◽  
Vol 78 (3) ◽  
pp. 481-486 ◽  
Author(s):  
Hidenori Kobayashi ◽  
Hisashi Ide ◽  
Hiroshi Aradachi ◽  
Yoshikazu Arai ◽  
Yuji Handa ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Cerebral Artery ◽  
Cell Damage ◽  
Blood Clot ◽  
Autologous Blood ◽  
Transluminal Angioplasty ◽  
Content Type ◽  
Histological Studies ◽  
The Right ◽  
Chronic Cerebral Vasospasm

✓ Percutaneous transluminal angioplasty for treatment of cerebral vasospasm was performed in primates. Chronic cerebral vasospasm was induced by placement of an autologous blood clot over the right internal carotid artery (ICA), middle cerebral artery (MCA), and anterior cerebral artery (ACA). Cerebral angiography on Day 7 showed that the diameters of the ICA, MCA, and ACA were reduced to 55.7% ± 1.3%, 55.3% ± 2.6%, and 59.6% ± 1.3%, respectively, of baseline. The angioplasty was carried out with a silicone microballoon attached to a microcatheter under somatosensory evoked potential (SEP) monitoring on Day 7. The angioplasty for ICA was performed satisfactorily; however, the balloon could be not advanced to the spastic M1 or A1 portions of the cerebral artery. Following angioplasty, the diameters of the ICA, the M1 segment, and the A1 segment were 79.6% ± 2.9% (p < 0.001), 67.6% ± 4.3% (p < 0.05), and 61.7% ± 2.2% (not significant), respectively, of baseline. Histological studies demonstrated that the vessels were well dilated and patent without endothelial cell damage.

Time course of the impairment of cerebral autoregulation during chronic cerebral vasospasm after subarachnoid hemorrhage in primates

1992 ◽  
Vol 76 (3) ◽  
pp. 493-501 ◽  
Author(s):  
Yuji Handa ◽  
Minoru Hayashi ◽  
Hiroaki Takeuchi ◽  
Tetsuya Kubota ◽  
Hidenori Kobayashi ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Cerebral Autoregulation ◽  
Time Course ◽  
Blood Clot ◽  
Autologous Blood ◽  
Conduction Time ◽  
Arterial Blood ◽  
The Right ◽  
Chronic Cerebral Vasospasm

✓ The time course of the impairment of cerebral autoregulation during chronic cerebral vasospasm after subarachnoid hemorrhage was studied in 18 monkeys. Changes in cerebral blood flow (CBF) at the regional level and central conduction times during either graded hypo- or hypertension were evaluated in these animals at three stages (3, 7, and 14 days) following the introduction of an autologous blood clot around the right middle cerebral artery (MCA). Angiograms revealed a reduction in vessel caliber (compared to the baseline level in the involved MCA) of 30% at 3 days, 50% at 7 days, and 10% at 14 days. At all stages, CBF remained constant at mean arterial blood pressures (MABP) of 60 to 160 mm Hg in the noninvolved hemisphere. In contrast, at the 3- and 7-day stages, there was an impairment of autoregulation in the involved hemisphere at MABP of 40 to 180 mm Hg. The right hemispheric CBF was significantly (p < 0.05) lower than that in the left throughout the period of investigation at MABP below 120 mm Hg, but rose to exceed the left CBF at MABP above 180 mm Hg at the 7-day stage and 160 mm Hg at the 14-day stage. The right-sided central conduction time showed significant (p < 0.05) prolongation at MABP below 60 mm Hg at the 3-day stage and 40 mm Hg at the 7-day stage. It is suggested that these results may help to develop guidelines for hemodynamic therapy for vasospasm in its various stages.

Etiology of cerebral vasospasm in primates

1991 ◽  
Vol 75 (3) ◽  
pp. 415-424 ◽  
Author(s):  
R. Loch Macdonald ◽  
Bryce K. A. Weir ◽  
Tim D. Runzer ◽  
Michael G. A. Grace ◽  
J. Max Findlay ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Carotid Arteries ◽  
Internal Carotid ◽  
Autologous Blood ◽  
Supernatant Fluid ◽  
Primate Model ◽  
Content Type ◽  
The Right ◽  
Internal Carotid Arteries ◽  
Angiographic Findings

✓ A primate model was used to determine whether oxyhemoglobin (OxyHb), methemoglobin (MetHb), or bilirubin is likely to be responsible for cerebral vasospasm following subarachnoid hemorrhage (SAH). Forty cynomolgus monkeys were randomly assigned to one of five groups. On Day 0, each animal underwent angiography followed by right craniectomy and placement of an Ommaya reservoir with its catheter adjacent to the right middle cerebral artery (MCA). The animals received intrathecal injections twice a day for 6 days of one of the following solutions: mock cerebrospinal fluid (CSF); OxyHb; MetHb; bilirubin; or supernatant fluid from an incubated mixture of autologous blood and mock CSF. On Day 7, angiography was repeated and the animals were killed. Comparison of angiograms obtained on Day 0 and Day 7 of the experiment showed significant vasospasm of the right MCA and the right anterior cerebral and internal carotid arteries in the animal groups that had received OxyHb or supernatant fluid. There was a smaller reduction in diameter of the same vessels in the bilirubin group (not statistically significant), while no effects were observed in the groups receiving MetHb or mock CSF. Electron microscopy of the right MCA's gave results consistent with the angiographic findings. One monkey in the OxyHb group developed a delayed-onset right MCA infarction. These data suggest that OxyHb is the cause of cerebral vasospasm following SAH.

Loss of nitric oxide synthase immunoreactivity in cerebral vasospasm

1996 ◽  
Vol 84 (4) ◽  
pp. 648-654 ◽  
Author(s):  
Ryszard M. Pluta ◽  
B. Gregory Thompson ◽  
Ted M. Dawson ◽  
Solomon H. Snyder ◽  
Robert J. Boock ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cerebral Vasospasm ◽  
Cerebral Artery ◽  
Cerebral Arteries ◽  
Nerve Fibers ◽  
Content Type ◽  
The Right ◽  
Oxide Synthase ◽  
Fine Print

✓ To determine the distribution of nitric oxide synthase (NOS) in the primate cerebral artery nervi vasorum and to examine the potential role of NOS in cerebral vasospasm after subarachnoid hemorrhage (SAH) in primates, the distribution of NOS immunoreactivity (NOS-IR) in the major cerebral arteries was examined immunohistochemically in cynomolgus monkeys by the use of whole, mounted preparations of the circle of Willis. In four normal monkeys, NOS-IR was localized to the endothelial and adventitial layers of the large cerebral arteries. On the abluminal side, NOS-IR staining was densely concentrated in perivascular nerve fibers (nervi vasorum) of the anterior circulation. Staining was less prominent in the posterior circulation. In six monkeys with vasospasm on Day 7 after placement of preclotted arterial blood to form an SAH around the right middle cerebral artery (MCA) (42% ± 8.3% decrease of MCA area, mean ± standard deviation), NOS-IR was virtually absent in nerve fibers around the spastic right MCA but was normal on the contralateral side. In five monkeys in which vasospasm resolved by Day 14 after SAH (36% ± 14% decrease of right MCA area on Day 7, and 5% ± 14% decrease on Day 14), NOS-IR was also absent in the right MCA adventitial nerve fibers and remained normal in the left MCA. Adventitial NOS-IR was also normal in cerebral vessels of a sham-operated, nonspastic monkey. These findings provide further evidence that nitric oxide (NO) functions as a neuronal transmitter to mediate vasodilation in primates and indicate a role for adventitial NO in the pathogenesis of cerebral vasospasm after SAH in humans.

Prospective, randomized, double-blind trial of BQ-123 and bosentan for prevention of vasospasm following subarachnoid hemorrhage in monkeys

1995 ◽  
Vol 83 (3) ◽  
pp. 503-509 ◽  
Author(s):  
Akihiko Hino ◽  
Bryce K. A. Weir ◽  
R. Loch Macdonald ◽  
Ronald A. Thisted ◽  
Chul-Jin Kim ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Artery ◽  
Internal Carotid ◽  
Blood Clot ◽  
Autologous Blood ◽  
Ommaya Reservoir ◽  
Double Blind ◽  
The Right ◽  
Arterial Diameters

✓ Thirty-one monkeys were randomly divided into three groups to undergo baseline cerebral angiography followed by induction of subarachnoid hemorrhage by placement of autologous blood clot along the right-sided arteries of the anterior circle of Willis (Day 0). The monkeys were then given drug vehicle or one of two endothelin (ET) antagonists, BQ-123 (6 mg/kg/day) or bosentan (5 mg/kg/day) intracisternally. The BQ-123 was administered by continuous infusion from a subcutaneous pump and the bosentan was given by twice-daily injections into an Ommaya reservoir in the subcutaneous space with a catheter along the right middle cerebral artery (MCA). Seven days later (Day 7), angiography was repeated and the animals were killed. Comparison of arterial diameters shown on angiograms between Day 0 and Day 7 groups given placebo and bosentan showed significant reductions in the diameters of the right intradural internal carotid (28% ± 6% and 30% ± 6%, respectively, paired t-test, p < 0.05), anterior cerebral artery (29% ± 8% and 32%, ± 6% respectively ± 6%, respectively) and MCA (34% ± 6% and 46% ± 4%, respectively). Animals injected with BQ-123 had significant narrowing of the right extradural internal carotid artery (7% ± 6%) and the basilar artery (11% ± 3%), but not of the right MCA. Comparison of arterial diameters between groups at Day 7 showed significant variance in the right extradural internal carotid, both intradural internal carotid, right middle cerebral, and left anterior cerebral arteries; the animals injected with BQ-123 developed significantly less arterial narrowing these those receiving bosentan and placebo. Bosentan was not detected in the cerebrospinal fluid aspirated from the cisterna magna on Day 7, whereas BQ-123 was detected in two animals. We can infer from these results that BQ-123 prevents vasospasm following subarachnoid hemorrhage in monkeys, that further investigations of ET antagonists are warranted, and that ET may be an important pathophysiological mediator of vasospasm. The lack of efficacy of bosentan may be related to inadequate cerebrospinal fluid levels obtained by administration twice-daily through an Ommaya reservoir.

Prevention of chronic experimental cerebral vasospasm with ibuprofen and high-dose methylprednisolone

1983 ◽  
Vol 59 (6) ◽  
pp. 925-932 ◽  
Author(s):  
Douglas Chyatte ◽  
Nancy Rusch ◽  
Thoralf M. Sundt
Keyword(s):  
Smooth Muscle ◽  
Cerebral Vasospasm ◽  
Autologous Blood ◽  
Barium Chloride ◽  
High Dose ◽  
Content Type ◽  
High Dose Methylprednisolone ◽  
Prostaglandin F ◽  
Basilar Arteries ◽  
Chronic Cerebral Vasospasm

✓ Severe chronic cerebral vasospasm was reliably induced in dogs by two injections, 2 days apart, of autologous blood into the cisterna magna. Treatment with ibuprofen or high-dose methylprednisolone after the first injection prevented or reduced vasospasm. Both drugs reduced meningismus and accelerated the rate of neurological recovery. Compared with specimens from normal dogs, rings of basilar arteries obtained from untreated dogs contracted weakly in response to 5-hydroxytryptamine, prostaglandin F2α, potassium chloride, and barium chloride. Rings of arteries from dogs who received ibuprofen or methylprednisolone contracted more strongly. Electron micrographs of basilar arteries from untreated dogs showed degeneration of smooth muscle, whereas those from treated dogs did not. Thus, what is termed “chronic cerebral vasospasm” probably represents a structural derangement of the blood vessel wall leading to its narrowing, rather than a sustained contraction of the vascular smooth muscle. Administration of high-dose methylprednisolone and ibuprofen can prevent its occurrence.

The effect of timing of clot removal on chronic vasospasm in a primate model

1987 ◽  
Vol 67 (4) ◽  
pp. 558-564 ◽  
Author(s):  
Yuji Handa ◽  
Bryce K. A. Weir ◽  
Michael Nosko ◽  
Russ Mosewich ◽  
Tsutomu Tsuji ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Subarachnoid Space ◽  
Blood Clot ◽  
Autologous Blood ◽  
Cerebral Arteries ◽  
Neurological Deficits ◽  
Physiological Status ◽  
Cerebral Vessel ◽  
Clot Removal ◽  
Chronic Cerebral Vasospasm

✓ The effect of complete clot removal at times from 48 to 96 hours after subarachnoid hemorrhage (SAH) on the development of chronic cerebral vasospasm was evaluated to determine whether there is a critical point after which clot removal is ineffective in preventing vasospasm. Thirty cynomolgus monkeys were randomized to one of five groups: sham-operated group, clot removal at 48 hours after SAH (48-hour group), clot removal at 72 hours after SAH (72-hour group), clot removal at 96 hours after SAH (96-hour group), and clot placement only (clot group). Standard microsurgical techniques were used to dissect bilaterally the major cerebral arteries free of arachnoid. An autologous blood clot averaging 4.2 gm was placed around the vessels in the subarachnoid space of the monkeys in the 48-hour, 72-hour, 96-hour, and clot groups. Physiological saline was instilled into the subarachnoid space of the sham-operated animals. Animals in the clot-removal groups underwent surgical clot removal at the determined times for each group. Two animals in each of the sham-operated and clot groups were subjected to reoperation at each of 48, 72, and 96 hours after SAH. The incisions were reopened and then simply reclosed. Neurological status, angiographic cerebral vessel caliber, and physiological status were evaluated before and 7 days after SAH induction. There were no significant neurological deficits in the sham-operated, 48-hour, or 72-hour groups. Two animals in each of the 96-hour and clot groups showed deterioration in level of consciousness developing on Day 4 or 5 after SAH induction. All the major cerebral arteries of the animals in the clot and 96-hour groups showed significant vasospasm (p < 0.01) on Day 7. Animals in the 72-hour group had significant vasospasm (p < 0.05) of the internal carotid and middle cerebral arteries but not the anterior cerebral arteries. There was no significant vasospasm (p > 0.05) in any of the cerebral arteries in the 48-hour group. Severity of vasospasm paralleled the duration of contact between the blood clot and the cerebral vessels. Evacuation of the subarachnoid hematoma later than 48 hours after SAH resulted in no significant reduction in the degree of chronic cerebral vasospasm. It is suggested that clot removal at early operation is likely to be useful only if it is performed within 48 hours of SAH.

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.

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor—mediated contraction

2005 ◽  
Vol 102 (6) ◽  
pp. 1101-1107 ◽  
Author(s):  
Hartmut Vatter ◽  
Michael Zimmermann ◽  
Veronika Tesanovic ◽  
Andreas Raabe ◽  
Lothar Schilling ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Vasospasm ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Affinity Constant ◽  
Dependent Manner ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature. Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2). The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−). Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

A randomized placebo-controlled double-blind trial of nimodipine after SAH in monkeys

1984 ◽  
Vol 60 (6) ◽  
pp. 1176-1185 ◽  
Author(s):  
Francisco Espinosa ◽  
Bryce Weir ◽  
Theodor Shnitka ◽  
Thomas Overton ◽  
Donald Boisvert
Keyword(s):  
Blood Clot ◽  
Autologous Blood ◽  
Ultrastructural Changes ◽  
Wall Thickening ◽  
Fish Scale ◽  
Double Blind ◽  
Content Type ◽  
Arterial Perfusion ◽  
Basilar Arteries ◽  
Trial Drug

✓ Chronic cerebral vasospasm was induced in monkeys by placement of an autologous blood clot after the basal cisterns had been opened over the arteries of the circle of Willis on one side. The experimental protocol was detailed in Part 1 of this paper. Twenty of the 30 monkeys studied from both groups (one receiving placebo and the other nimodipine) underwent cerebral fixation (Day 14) at controlled pressure by intra-arterial perfusion. The arteries at the base of the brain were studied by light microscopy and scanning (SEM) and transmission electron microscopy (TEM). Cerebral angiography on Day 7 showed that vasospasm was significantly more common (p < 0.0001) and more severe (p < 0.01) on the clot side compared to the control or non-clot side. Vasospasm was less severe on Day 14, just before sacrifice. On SEM, 80% of the 20 middle cerebral artery (MCA) specimens that had been in spasm (Day 7) showed marked corrugation, and in some the endothelium had a fish-scale appearance. All of the 10 MCA's on the clot side examined by TEM that had been in spasm (Day 7) showed marked changes such as endothelial swelling, subendothelial proliferation, corrugation of the elastic lamina, and myonecrosis. With few exceptions, none of the basilar arteries or MCA's on the non-clot (control) side showed any abnormalities. The pathological findings of vessels in spasm were considered to be slightly less severe in the nimodipine group; however, the trial drug (1 mg/kg/8 hrs) did not prevent such abnormalities from occurring. The ultrastructural changes in the arterial walls of specimens from both placebo and nimodipine groups in vasospasm are described. Since dramatic changes are present in the vessel walls even after radiologically visible vasospasm has almost completely abated, we believe that vasospasm is due to long-lasting smooth-muscle constriction and not to vessel wall thickening caused by a cellular or subcellular infiltrate.

Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats

2004 ◽  
Vol 101 (1) ◽  
pp. 104-107 ◽  
Author(s):  
Donald Seyfried ◽  
Yuxia Han ◽  
Dunyue LU ◽  
Jieli Chen ◽  
Ali Bydon ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Autologous Blood ◽  
Cell Loss ◽  
Study Data ◽  
Content Type ◽  
Ipsilateral Striatum ◽  
The Right ◽  
Higher Doses ◽  
Fine Print

Object. Atorvastatin, a β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitor, improves neurological functional outcome, reduces cerebral cell loss, and promotes regional cellular plasticity when administered after intracerebral hemorrhage (ICH) in rats. Methods. Autologous blood was stereotactically injected into the right striatum in rats, and atorvastatin was administered orally beginning 24 hours after ICH and continued daily for 1 week. At a dose of 2 mg/kg, atorvastatin significantly reduced the severity of neurological deficit from 2 to 4 weeks after ICH. The area of cell loss in the ipsilateral striatum was also significantly reduced in these animals. Consistent with previous study data, higher doses of atorvastatin (8 mg/kg) did not improve functional outcome or reduce the extent of injury. Histochemical stains for markers of synaptogenesis, immature neurons, and neuronal migration revealed increased labeling in the region of hemorrhage in the atorvastatin-treated rats. Conclusions. Analysis of the data in this study indicates that atorvastatin improves neurological recovery after experimental ICH and may do so in part by increasing neuronal plasticity.

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