Blood Clot Placement Model of Subarachnoid Hemorrhage in Non-human Primates

2014 ◽  
pp. 343-346
Author(s):  
Ali Reza Fathi ◽  
Kamran D. Bakhtian ◽  
Serge Marbacher ◽  
Javier Fandino ◽  
Ryszard M. Pluta
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Blood Clot

scholarly journals Clinical condition of 120 patients alive at 3 years after poor-grade aneurysmal subarachnoid hemorrhage

2021 ◽  
Author(s):  
Anniina H. Autio ◽  
Juho Paavola ◽  
Joona Tervonen ◽  
Maarit Lång ◽  
Terhi J. Huuskonen ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Clinical Condition ◽  
Hospice Care ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Blood Clot ◽  
Neurointensive Care ◽  
Intracerebral Hematoma ◽  
Poor Grade ◽  
Final Study ◽  
Study Population

Abstract Background To study the clinical condition of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients alive at 3 years after neurointensive care. Methods Of the 769 consecutive aSAH patients from a defined population (2005–2015), 269 (35%) were in poor condition on admission: 145 (54%) with H&H 4 and 124 (46%) with H&H 5. Their clinical lifelines were re-constructed from the Kuopio Intracranial Aneurysm Database and Finnish nationwide registries. Of the 269 patients, 155 (58%) were alive at 14 days, 125 (46%) at 12 months, and 120 (45%) at 3 years. Results The 120 H&H 4–5 patients alive at 3 years form the final study population. On admission, 73% had H&H 4 but only 27% H&H 5, 59% intracerebral hematoma (ICH; median 22 cm3), and 26% intraventricular blood clot (IVH). The outcome was favorable (mRS 0–1) in 45% (54 patients: ICH 44%; IVH clot 31%; shunt 46%), moderate (mRS 2–3) in 30% (36 patients: ICH 64%; IVH clot 19%; shunt 42%), and unfavorable (mRS 4–5) in 25% (30 patients: ICH 80%; IVH clot 23%; shunt 50%). A total of 46% carried a ventriculoperitoneal shunt. ICH volume was a significant predictor of mRS at 3 years. Conclusions Of poor-grade aSAH patients, 45% were alive at 3 years, even 27% of those extending to pain (H&H 5). Of the survivors, 75% were at least in moderate condition, while only 2.6% ended in hospice care. Consequently, we propose non-selected admission to neurointensive care (1) for a possibility of moderate outcome, and (2), in case of brain death, possibly improved organ donation rates.

Disturbed Cerebrospinal Fluid Circulation after Subarachnoid Hemorrhage and Acute Aneurysm Surgery

Neurosurgery ◽  
1990 ◽  
Vol 26 (5) ◽  
pp. 804-809 ◽  
Author(s):  
Ludwig M. Auer ◽  
Michael Mokry
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Blood Clot ◽  
Cerebral Aneurysms ◽  
External Ventricular Drainage ◽  
Easy Access ◽  
Cerebrospinal Fluid Circulation ◽  
Aneurysm Dissection ◽  
Subarachnoid Blood ◽  
The Brain

Abstract In 138 patients with ruptured cerebral aneurysms operated on within 48 to 72 hours after subarachnoid hemorrhage, an external ventricular drainage catheter was inserted before craniotomy and was used intermittently during the first week after surgery. In 51 patients, intracranial pressure (ICP) was measured intraoperatively. The majority of patients showed increased ICP intraoperatively irrespective of the preoperative Hunt and Hess grade and the amount of subarachnoid blood accumulation or intraventricular blood clot. Intraoperative drainage of cerebrospinal fluid allowed easy access for aneurysm dissection by making the brain slack in more than 90% of patients. Postoperative ICP measurements revealed that significant brain swelling did not occur in the majority of patients, In 7 patients, persistently elevated ICP (>20 mm Hg) was recorded. Nine patients (8%) developed shunt-dependent hydrocephalus; all of these patients had suffered an intraventricular hemorrhage. Measurements of the volumes of cerebrospinal fluid drained did not allow prediction of shunt-dependent hydrocephalus.

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.

Cerebral perivascular nerves in subarachnoid hemorrhage

1986 ◽  
Vol 65 (4) ◽  
pp. 531-539 ◽  
Author(s):  
Hideaki Hara ◽  
Michael Nosko ◽  
Bryce Weir
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Blood Clot ◽  
Autologous Blood ◽  
Nerve Fibers ◽  
Content Type ◽  
Arterial Blood ◽  
Mild Reduction ◽  
Perivascular Nerves ◽  
Basilar Arteries ◽  
Repeat Angiography

✓ The authors have studied the changes induced by subarachnoid hemorrhage (SAH) in the density and distribution of cerebral perivascular nerves in monkeys and rats. The SAH was induced in monkeys by placement of an autologous blood clot after opening the basal cisterns over the arteries of the circle of Willis on one side. In the rat study, SAH was induced by injection of autologous arterial blood into the cisterna magna. The nerves examined were adrenergic nerves, acetylcholinesterase (AChE)-containing nerves, vasoactive intestinal polypeptide (VIP)-like immunoreactive nerves, and substance P-like immunoreactive nerves. In the monkey study, all animals underwent baseline cerebral angiography, then had repeat angiography just before sacrifice on Day 2, 7, 28, or 70 after SAH. Two sham-operated monkeys underwent the surgical procedure without clot placement and were sacrificed on postoperative Day 7, after repeat angiography. Clot placement in monkeys reduced staining of all middle cerebral artery (MCA) perivascular nerves for between 2 and 28 days post-SAH. The number of stained nerve fibers of MCA's on the non-operated side was slightly reduced on Days 2 and 7 after SAH. Sham-operated monkeys showed a mild reduction of staining in all nerves, but only on the operated side. Cerebral vasospasm was observed on all angiograms taken on Days 2 and 7 following SAH. No vasospasm was found in normal or sham-operated monkeys. The disappearance of nerve staining without associated vasospasm was found on the operated side of the sham-operated monkeys and on the clot side of the animal sacrificed on Day 28 after SAH. Rats sacrificed on Days 2 and 7 post-SAH showed reduction in adrenergic and VIP-like immunoreactive staining around basilar arteries, while nerves containing AChE were not affected. Saline-injected rats exhibited no change in the appearance of perivascular innervation. These results suggest that SAH as well as surgical manipulation of the vessel wall caused a reduction of the studied substances in cerebral perivascular nerves. This reduction in immunoreactive staining of perivascular nerves did not correlate with the development of angiographic vasospasm after SAH.

scholarly journals Early permanent cerebrospinal fluid diversion lowers the rate of nosocomial meningitis in aneurysmal subarachnoid hemorrhage

2020 ◽  
Author(s):  
Davide Marco Croci ◽  
Martina Dalolio ◽  
Soheila Aghlmandi ◽  
Ethan Taub ◽  
Daniel Zumofen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Blood Clot ◽  
Delayed Cerebral Ischemia ◽  
Infectious Complications ◽  
Detectable Effect ◽  
Catheter Colonization ◽  
Delayed Cerebral Vasospasm ◽  
Csf Diversion

Abstract Background: Early permanent cerebrospinal fluid (CSF) diversion for hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) might shorten the duration of external ventricular drainage (EVD) and thereby reduce infectious complications. The potential effect on the rate of delayed cerebral vasospasm (DCVS) and associated morbidity has not been studied to date. The objective of this study was to detect any association with EVD-associated infections (EVDAI), symptomatic DCVS, or delayed cerebral ischemia (DCI) by the time of hospital discharge. Methods: A single-center dataset of aSAH patients who received a permanent CSF diversion procedure between 2009 and 2018 was used for the evaluation. The subjects were divided into an “early group” if such a procedure was performed up to 14 days after the ictus, and a “late group” if it was performed from the 15 th day onward. The statistical analysis employed univariable and multivariable logistic regression models. Results: Among 274 consecutive aSAH patients, 39 (14.2 %) had a permanent CSF diversion procedure. While the blood clot burden was similarly distributed, patients with early permanent CSF diversion (20 out of 39, 51.2%) had higher levels of consciousness on admission. Early permanent CSF diversion was associated with a shorter duration of EVD (OR 0.73, 95%CI 0.58-0.92 per day). Higher catheter colonization to EVDAI ratio (1/7 out of 20 vs. 7/7 out of 19) and a markedly lower frequency of EVDAI (OR 0.08, 95 %CI 0.01-0.80) were detected. The prevalence (5 vs. 37) and the cumulative incidence (3 vs. 18) of EVDAI were remarkably lower in patients receiving early permanent CSF diversion. The occurrence of CSF-diversion device obstruction, the rate of symptomatic DCVS (OR 0.61, 95 %CI 0.16-2.27) or detected DCI on computed tomography (OR 0.35, 95 %CI 0.08-1.47), and the likelihood of a poor outcome at discharge did not differ between the two groups (OR 0.88, 95%CI 0.24-3.22). Conclusions: Early permanent CSF diversion in good grade aSAH patients is associated with a shorter duration of EVD, lower catheter colonization rates, and fewer infectious complications. The timing of permanent CSF diversion had no detectable effect on DCVS-related morbidity. These findings need to be confirmed in larger cohorts.

scholarly journals Alterations in Serotonin and Neuropeptide Y Content of Cerebrovascular Sympathetic Nerves following Experimental Subarachnoid Hemorrhage

1989 ◽  
Vol 9 (3) ◽  
pp. 271-279 ◽  
Author(s):  
A. Jackowski ◽  
A. Crockard ◽  
G. Burnstock ◽  
J. Lincoln
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Neuropeptide Y ◽  
Sympathetic Nerve ◽  
Blood Clot ◽  
Cerebral Arteries ◽  
Immunohistochemical Analysis ◽  
Sympathetic Nerves ◽  
Nerve Fibers ◽  
Arterial Blood ◽  
Experimental Subarachnoid Hemorrhage

The effect of an experimental subarachnoid hemorrhage (SAH) upon neurotransmitter content in sympathetic nerves supplying the major cerebral arteries of the rat has been examined by immunohistochemical analysis and high performance liquid chromatography with electrochemical detection (HPLC–ECD). In particular, changes that occur in sympathetic nerve content of the vasoconstrictor agents serotonin (5-HT) and neuropeptide Y (NPY), which are colocalized with noradrenaline, were assessed. Subarachnoid hemorrhage was induced by a single injection of autologous arterial blood into the cerebrospinal fluid (CSF) space of the cisterna magna. The density of 5-HT-containing and NPY-containing perivascular nerve fibers per unit area of vessels was measured at defined intervals from 15 min to 5 days post-SAH. In addition, an HPLC study was performed to quantify the actual amounts of 5-HT and noradrenaline present in circle of Willis vessels at 3 h post-SAH. Comparison was made with sham-operated animals and animals that received a cisternal injection of buffered saline in place of blood. Our results reveal a major increase in cerebrovascular sympathetic nerve content of serotonin, arising by uptake, presumably from subarachnoid blood clot, within the first 3 h post-SAH. Neuropeptide Y content, however, decreased from 3 up to 48 h posthemorrhage. By 3 days post-SAH, when the majority of subarachnoid clot had resorbed, the sympathetic nerve content of both NPY and 5-HT was restored to normal. This pattern of change was not observed in either sham-operated or saline-injected controls.

Grading of Subarachnoid Hemorrhage: Modification of the World Federation of Neurosurgical Societies Scale on the Basis of Data for a Large Series of Patients

Neurosurgery ◽  
2004 ◽  
Vol 54 (3) ◽  
pp. 566-576 ◽  
Author(s):  
David S. Rosen ◽  
R. Loch Macdonald
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Randomized Clinical Trials ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Blood Clot ◽  
Prognostic Significance ◽  
World Federation ◽  
Computed Tomographic ◽  
The World ◽  
History Of ◽  
Grading Scale

Abstract OBJECTIVE The goals of this study were to use a large, prospectively collected, multicenter database for patients with aneurysmal subarachnoid hemorrhage (SAH) who were treated between 1991 and 1997 to determine the prognostic significance of clinical and radiological factors for outcomes and to use those factors to develop a grading scale to predict outcomes. METHODS A total of 3567 patients with SAH who were entered into four randomized clinical trials of tirilazad were studied. Outcomes were assessed 3 months after SAH, with the Glasgow Outcome Scale. Twenty clinical and radiological factors were entered into univariate and multivariate analyses, to determine factors prognostic for outcomes. Grading scales based on the most powerful prognostic parameters were statistically derived and validated and were compared with the World Federation of Neurosurgical Societies (WFNS) grading scale. RESULTS Factors predictive of outcomes included age, WFNS grade, history of hypertension, systolic blood pressure at admission, ruptured aneurysm location and size, blood clot thickness on computed tomographic scans, and angiographic vasospasm at admission. A grading scale using these factors could be derived; it predicted outcomes more accurately than did the WFNS scale, although it would be more complex to use. CONCLUSION Outcome prediction after SAH can be improved by adding additional clinical and radiological factors to the WFNS scale, albeit with added complexity.

scholarly journals Intrathecal Fibrinolytic Therapy after Subarachnoid Hemorrhage: Dosage Study in a Primate Model and Review of the Literature

1989 ◽  
Vol 16 (1) ◽  
pp. 28-40 ◽  
Author(s):  
J.M. Findlay ◽  
B.K.A. Weir ◽  
K. Kanamaru ◽  
M. Grace ◽  
P. Gordon ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Dose Group ◽  
Blood Clot ◽  
Cerebral Arteries ◽  
Recombinant Tissue Plasminogen Activator ◽  
Fibrinolytic Therapy ◽  
Primate Model ◽  
High Concentrations ◽  
Dosage Study ◽  
Erythrocyte Clearance

ABSTRACT:Because of the naturally low fibrinolytic activity of CSF many erythrocytes entrapped in subarachnoid blood clot undergo hemolysis in situ, releasing vasogenic oxyhemoglobin (OxyHb) in high concentrations around the basal cerebral arteries. In order to promote more rapid clearance of erythrocytes from the basal subarachnoid cisterns we are currently investigating intrathecal thrombolytic therapy with human, recombinant, tissue plasminogen activator (rt-PA) in a primate model of subarachnoid hemorrhage (SAH) and cerebral vasospasm (VSP). In the present study 16 monkeys were divided into 4 groups of 4, and each group received a different dose of sustained-release gel rt-PA at the time of experimental SAH. Cerebral angiography seven days later showed that whereas no VSP occurred in the groups receiving 0.5 or 0.75 mg of rt-PA, mild to moderate VSP occurred in the groups receiving 0.125 or 0.25 mg of rt-PA. Analysis of the combined 2 smaller dosage groups revealed significant (P<0.05) reduction of lumen caliber in the clotside internal carotid (C3 and C4), proximal anterior cerebral (A1) and middle cerebral (MCA) arteries. Gross subarachnoid clot remained in all of the animals in the 0.125 and 0.25 mg dose groups, in 2 of the animals in the 0.5 mg dose group, and none of the animals in the 0.75 mg dose group. It was concluded that 0.75 mg of gel rt-PA is sufficient to completely lyse a 4.25 ml SAH and prevent VSP in our primate model. The literature on fibrinolysis and erythrocyte clearance in cerebrospinal fluid (CSF) is reviewed.

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.

scholarly journals Reversal of cerebral vasospasm via intravenous sodium nitrite after subarachnoid hemorrhage in primates

2011 ◽  
Vol 115 (6) ◽  
pp. 1213-1220 ◽  
Author(s):  
Ali Reza Fathi ◽  
Ryszard M. Pluta ◽  
Kamran D. Bakhtian ◽  
Meng Qi ◽  
Russell R. Lonser
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Sodium Nitrite ◽  
Whole Blood ◽  
Intravenous Infusion ◽  
Blood Clot ◽  
Vessel Diameter ◽  
Aneurysm Rupture ◽  
Saline Infusion ◽  
Similar Treatment

Object Subarachnoid hemorrhage (SAH)-induced vasospasm is a significant underlying cause of aneurysm rupture-related morbidity and death. While long-term intravenous infusion of sodium nitrite (NaNO2) can prevent cerebral vasospasm after SAH, it is not known if the intravenous administration of this compound can reverse established SAH-induced vasospasm. To determine if the intravenous infusion of NaNO2 can reverse established vasospasm, the authors infused primates with the compound after SAH-induced vasospasm was established. Methods Subarachnoid hemorrhage–induced vasospasm was created in 14 cynomolgus macaques via subarachnoid implantation of a 5-ml blood clot. On Day 7 after clot implantation, animals were randomized to either control (saline infusion, 5 monkeys) or treatment groups (intravenous NaNO2 infusion at 300 μg/kg/hr for 3 hours [7 monkeys] or 8 hours [2 monkeys]). Arteriographic vessel diameter was blindly analyzed to determine the degree of vasospasm before, during, and after treatment. Nitric oxide metabolites (nitrite, nitrate, and S-nitrosothiols) were measured in whole blood and CSF. Results Moderate-to-severe vasospasm was present in all animals before treatment (control, 36.2% ± 8.8% [mean ± SD]; treatment, 45.5% ± 12.5%; p = 0.9). While saline infusion did not reduce vasospasm, NaNO2 infusion significantly reduced the degree of vasospasm (26.9% ± 7.6%; p = 0.008). Reversal of the vasospasm lasted more than 2 hours after cessation of the infusion and could be maintained with a prolonged infusion. Nitrite (peak value, 3.7 ± 2.1 μmol/L), nitrate (18.2 ± 5.3 μmol/L), and S-nitrosothiols (33.4 ± 11.4 nmol/L) increased significantly in whole blood, and nitrite increased significantly in CSF. Conclusions These findings indicate that the intravenous infusion of NaNO2 can reverse SAH-induced vasospasm in primates. Further, these findings indicate that a similar treatment paradigm could be useful in reversing cerebral vasospasm after aneurysmal SAH.

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