Reversal of cerebral vasospasm using an intrathecally administered nitric oxide donor

Object. Intrathecal bolus administration of (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen-1-ium-1,2-diolate (DETA/NO), a long half-life diazeniumdiolate-class nitric oxide (NO) donor, was evaluated for safety and efficacy in the treatment of delayed cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH). Methods. The baseline basilar artery (BA) diameter of 25 dogs was measured with the aid of angiography on Day 0. Vasospasm was then induced by intracisternal injection of autologous arterial blood on Days 0 and 2. Repeated arteriography on Day 7 revealed an average BA diameter of 58% of baseline. Each dog was then randomized to one of four groups: a pathology control group (SAH only, four animals); a treatment control group (SAH plus 2 µmol of the inactive drug carrier DETA, eight animals); a low-dose treatment group (SAH plus 0.2 µmol DETA/NO, six animals); or a high-dose treatment group (SAH plus 2 µmol DETA/NO, six animals). The drugs were administered in a 2-ml intrathecal bolus via the cisterna magna. Arterial caliber was monitored by angiography over the subsequent 4 hours. A 2-µmol dose of the drug was then given and serial arteriography continued for an additional hour to screen for tachyphylaxis. Intracranial pressure and respiratory and hemodynamic parameters were continuously monitored. Histopathological analyses of the animals' brains were performed after the dogs were killed on Day 8. The drug DETA/NO produced reversal of vasospasm in a dose-dependent fashion that roughly followed a double exponential time course. Doses of 2 µmol DETA/NO resulted in restoration of the angiographically monitored BA diameter to the prevasospasm size at 1.5 hours posttreatment, and this was sustained at 88% of baseline at 4 hours (p < 0.01, independent samples t-test). By contrast, the treatment control group remained on average at 54% of baseline diameter. The low-dose treatment group achieved only partial and more transitory relaxation. Histopathological analyses showed findings consistent with chronic SAH but did not demonstrate any toxicity associated with the NO donor. No adverse physiological changes were seen. Conclusions. This study indicates that long-acting NO donors are potentially useful as agents to restore circulation in patients suffering from cerebral vasospasm.

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Efficacy of multiple intraarterial papaverine infusions for improvement in cerebral circulation time in patients with recurrent cerebral vasospasm

Journal of Neurosurgery ◽

10.3171/jns.2004.100.3.0414 ◽

2004 ◽

Vol 100 (3) ◽

pp. 414-421 ◽

Cited By ~ 43

Author(s):

James K. Liu ◽

Michael S. Tenner ◽

Oren N. Gottfried ◽

Edwin A. Stevens ◽

Joshua M. Rosenow ◽

...

Keyword(s):

Cerebral Vasospasm ◽

Cerebral Circulation ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Primary Treatment ◽

Circulation Time ◽

Control Group ◽

Content Type ◽

The Mean ◽

Cerebral Circulation Time ◽

Fine Print

Object. Cerebral vasospasm that is caused by aneurysmal subarachnoid hemorrhage and that is refractory to maximal medical management can be treated with selective intraarterial papaverine infusions. The effects of single papaverine treatments on cerebral circulation time are well known. The purpose of this study was to assess the efficacy of multiple, repeated papaverine infusions on the cerebral circulation time in patients with recurrent vasospasm. Methods. A retrospective study was conducted in 17 patients who received multiple intraarterial papaverine infusions in 91 carotid artery (CA) territories for the treatment of cerebral vasospasm. Cerebral circulation times were measured from the first angiographic image, in which peak contrast was seen above the supraclinoid internal CA, to the peak filling of cortical veins. Glasgow Outcome Scale (GOS) scores assessed 12 months after discharge were reviewed. Cerebral circulation times in 16 CA territories were measured in a control group of 11 patients. Seventeen patients received a total of 91 papaverine treatments. Prolonged cerebral circulation times improved after 90 (99%) of 91 papaverine treatments. The prepapaverine mean cerebral circulation time was 6.54 seconds (range 3.35–27 seconds) and the immediate postpapaverine mean cerebral circulation time was 4.19 seconds (range 2.1–12.6 seconds), an overall mean decrease of 2.35 seconds (36%, p < 0.001). Recurrent vasospasm reflected by prolonged cerebral circulation times continued to improve with subsequent papaverine infusions. Repeated infusions were just as successful quantitatively as the primary treatment (mean change 2.06 seconds). The mean cerebral circulation time in the control group was 5.21 seconds (range 4–6.8 seconds). In five patients a dramatic reversal of low-attenuation changes was detected on computerized tomography scans. The mean GOS score at 12 months after discharge was 3.4. Conclusions. The preliminary results indicate that multiple intraarterial papaverine treatments consistently improve cerebral circulation times, even with repeated infusions in cases of recurrent vasospasm.

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Normobaric hyperoxia—induced improvement in cerebral metabolism and reduction in intracranial pressure in patients with severe head injury: a prospective historical cohort—matched study

Journal of Neurosurgery ◽

10.3171/jns.2004.101.3.0435 ◽

2004 ◽

Vol 101 (3) ◽

pp. 435-444 ◽

Cited By ~ 183

Author(s):

Christos M. Tolias ◽

Michael Reinert ◽

Rolf Seiler ◽

Charlotte Gilman ◽

Alexander Scharf ◽

...

Keyword(s):

Treatment Group ◽

Intracranial Pressure ◽

Historical Control Group ◽

Historical Control ◽

Control Group ◽

Historical Cohort ◽

Normobaric Hyperoxia ◽

Content Type ◽

Severe Tbi ◽

Fine Print

Object. The effect of normobaric hyperoxia (fraction of inspired O2 [FIO2] concentration 100%) in the treatment of patients with traumatic brain injury (TBI) remains controversial. The aim of this study was to investigate the effects of normobaric hyperoxia on five cerebral metabolic indices, which have putative prognostic significance following TBI in humans. Methods. At two independent neurointensive care units, the authors performed a prospective study of 52 patients with severe TBI who were treated for 24 hours with 100% FIO2, starting within 6 hours of admission. Data for these patients were compared with data for a cohort of 112 patients who were treated in the past; patients in the historical control group matched the patients in our study according to their Glasgow Coma Scale scores after resuscitation and their intracranial pressure within the first 8 hours after admission. Patients were monitored with the aid of intracerebral microdialysis and tissue O2 probes. Normobaric hyperoxia treatment resulted in a significant improvement in biochemical markers in the brain compared with the baseline measures for patients treated in our study (patients acting as their own controls) and also compared with findings from the historical control group. In the dialysate the glucose levels increased (369.02 ± 20.1 µmol/L in the control group and 466.9 ± 20.39 µmol/L in the 100% O2 group, p = 0.001), whereas the glutamate and lactate levels significantly decreased (p < 0.005). There were also reductions in the lactate/glucose and lactate/pyruvate ratios. Intracranial pressure in the treatment group was reduced significantly both during and after hyperoxia treatment compared with the control groups (15.03 ± 0.8 mm Hg in the control group and 12.13 ± 0.75 mm Hg in the 100% O2 group, p < 0.005) with no changes in cerebral perfusion pressure. Outcomes of the patients in the treatment group improved. Conclusions. The results of the study support the hypothesis that normobaric hyperoxia in patients with severe TBI improves the indices of brain oxidative metabolism. Based on these data further mechanistic studies and a prospective randomized controlled trial are warranted.

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Low-dose radiotherapy for the inhibition of peridural fibrosis after reexploratory nerve root decompression for postlaminectomy syndrome

Journal of Neurosurgery Spine ◽

10.3171/spi.2003.99.3.0271 ◽

2003 ◽

Vol 99 (3) ◽

pp. 271-277 ◽

Cited By ~ 5

Author(s):

Peter C. Gerszten ◽

John J. Moossy ◽

John C. Flickinger ◽

William C. Welch

Keyword(s):

Nerve Root ◽

Low Dose ◽

Radicular Pain ◽

Control Group ◽

Preoperative Irradiation ◽

External Beam Irradiation ◽

Content Type ◽

Peridural Fibrosis ◽

Nerve Root Decompression ◽

Fine Print

Object. The authors of clinical studies have demonstrated a significant association between the presence of extensive post—lumbar discectomy peridural scar formation and the recurrence of low-back and radicular pain. Low-dose perioperative radiotherapy has been demonstrated to inhibit peridural fibrosis after laminectomy in animal models. The present study was designed to evaluate the clinical efficacy of preoperative irradiation in patients with failed—back surgery syndrome due to peridural fibrosis who underwent reexploration and nerve root decompression. Methods. Ten patients with symptomatic post—discectomy peridural fibrosis were randomized. Half of the patients underwent 700-cGy external-beam irradiation to the operative site 24 hours prior to reexploration and decompressive treatment of their symptomatic nerve root(s) (treatment group) and the other half underwent reexploration and decompressive treatment without preoperative irradiation (control group). All patients underwent simulated irradiation so neither patient nor surgeon was aware of the patient's group. In all patients the antiadhesion product ADCON-L was placed over the affected nerve root at the time of surgery. Clinical outcome was assessed using the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Section Lumbar Disc Herniation Study Questionnaire at baseline, 6 weeks, 3 months, and 1 year follow up. Five men and five women (mean age 42 years) underwent randomization and surgery. Three patients underwent reexploration at L4–5, four at L5—S1, and three at both levels. No complication was associated with irradiation, and no new neurological deficits occurred. At 1-year follow-up examination, three irradiation-treated patients were pain free and two experienced improvement. In the control group, three patients experienced improved pain relief and two were unchanged. There was a trend toward better outcome at 1 year in the radiotherapy-treated group (p = 0.056). Conclusions. Preoperative low-dose external-beam irradiation improved clinical outcomes after reexploration and decompression of nerve roots affected by postlaminectomy peridural fibrosis causing radicular pain. The addition of preoperative irradiation may improve outcome in patients who undergo reoperation for recurrent radicular pain associated with a significant amount of peridural fibrosis, particularly now that no antiadhesion product is available for clinical use.

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

Journal of Neurosurgery ◽

10.3171/jns.2002.97.1.0129 ◽

2002 ◽

Vol 97 (1) ◽

pp. 129-135 ◽

Cited By ~ 6

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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Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.1998.88.3.0557 ◽

1998 ◽

Vol 88 (3) ◽

pp. 557-561 ◽

Cited By ~ 95

Author(s):

Ryszard M. Pluta ◽

John K. B. Afshar ◽

Robert J. Boock ◽

Edward H. Oldfield

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Blood Clot ◽

Saline Control ◽

Control Group ◽

Content Type ◽

Delayed Cerebral Vasospasm ◽

Arterial Blood ◽

Fine Print

Hemoglobin released from hemolysed erythrocytes has been postulated to be responsible for delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). However, the evidence is indirect and the mechanisms of action are unclear. Cerebrovascular tone is regulated by a dynamic balance of relaxing and contracting factors. Loss of the endothelium-derived relaxing factor—nitric oxide in the presence of oxyhemoglobin and overproduction of endothelin-1 stimulated by oxyhemoglobin have been postulated as causes of delayed cerebral vasospasm after SAH. Object. The authors aimed to investigate this hypothesis using in vivo microdialysis to examine time-dependent changes in the perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin in a primate model of SAH. Methods. Nine cynomolgus monkeys underwent right-sided frontotemporal craniectomy and placement of a semipermeable microdialysis catheter adjacent to the right middle cerebral artery (MCA). Saline (control group, three animals) or an arterial blood clot (SAH group, six animals) was then placed around the MCA and the catheter. Arteriographically confirmed vasospasm had developed in all animals with SAH but in none of the control animals on Day 7. The dialysate was collected daily for 12 days. Levels of oxyhemoglobin, deoxyhemoglobin, and methemoglobin were measured by means of spectrophotometry. Perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin peaked on Day 2 in the control monkeys and could not be detected on Days 5 to 12. Perivascular concentrations of oxyhemoglobin and deoxyhemoglobin peaked on Day 7 in the SAH group, at which time the concentrations in the dialysate were 100-fold higher than in any sample obtained from the control animals. Methemoglobin levels increased only slightly, peaking between Days 7 and 12, at which time the concentration in the dialysate was 10-fold higher than in samples from the control animals. Conclusions. This study provides in vivo evidence that the concentrations of oxyhemoglobin and deoxyhemoglobin increase in the cerebral subarachnoid perivascular space during the development of delayed cerebral vasospasm. The results support the hypothesis that oxyhemoglobin is involved in the pathogenesis of delayed cerebral vasospasm after SAH and implicate deoxyhemoglobin as a possible vasospastic agent.

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Using Social Network Sites to Boost Savoring: Positive Effects on Positive Emotions

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17176407 ◽

2020 ◽

Vol 17 (17) ◽

pp. 6407

Author(s):

Sen-Chi Yu ◽

Kennon M. Sheldon ◽

Wen-Ping Lan ◽

Jia-Huei Chen

Keyword(s):

Treatment Group ◽

University Students ◽

Positive Emotions ◽

Well Being ◽

Control Group ◽

Treatment Control ◽

Positive Effects ◽

Post Test ◽

Treatment Control Group

Research has demonstrated that positive interventions (PIs) can be effective in enhancing well-being. Our study used Facebook to conduct a PI based on savoring. Sixty-one university students in Taiwan were randomly assigned to undergo a three-week savoring PI, and 61 participants were assigned to a no-treatment control group. The results showed significantly enhanced positive affect in the treatment group compared to the control group, in both a post-test and a final follow-up, but no significant differences between the two groups in negative affect. The treatment group also displayed significantly lower depression in the post-test, which was not maintained at the follow-up. These results indicate that, for university students, a savoring intervention via Facebook can be an effective way of enhancing positive emotions.

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Evaluation of endorphin content in the CSF of patients with trigeminal neuralgia before and after Gasserian ganglion thermocoagulation

Journal of Neurosurgery ◽

10.3171/jns.1981.55.6.0935 ◽

1981 ◽

Vol 55 (6) ◽

pp. 935-937 ◽

Cited By ~ 5

Author(s):

Giuseppe Salar ◽

Salvatore Mingrino ◽

Marco Trabucchi ◽

Angelo Bosio ◽

Carlo Semenza

Keyword(s):

Cerebrospinal Fluid ◽

Trigeminal Neuralgia ◽

Control Group ◽

Gasserian Ganglion ◽

Content Type ◽

Group Of Seven ◽

Idiopathic Trigeminal Neuralgia ◽

Significant Difference ◽

Before And After ◽

Fine Print

✓ The β-endorphin content in cerebrospinal fluid (CSF) was evaluated in 10 patients with idiopathic trigeminal neuralgia during medical treatment (with or without carbamazepine) and after selective thermocoagulation of the Gasserian ganglion. These values were compared with those obtained in a control group of seven patients without pain problems. No statistically significant difference was found between patients suffering from trigeminal neuralgia and those without pain. Furthermore, neither pharmacological treatment nor surgery changed CSF endorphin values. It is concluded that there is no pathogenetic relationship between trigeminal neuralgia and endorphins.

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Prevention of cerebral vasospasm after SAH with a thromboxane synthetase inhibitor, OKY-1581

Journal of Neurosurgery ◽

10.3171/jns.1982.57.1.0074 ◽

1982 ◽

Vol 57 (1) ◽

pp. 74-82 ◽

Cited By ~ 70

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.

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Protective effects of histamine on Gq-mediated relaxation in regenerated endothelium

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00733.2013 ◽

2014 ◽

Vol 306 (2) ◽

pp. H286-H290 ◽

Cited By ~ 4

Author(s):

Calvin K. Chan ◽

Song Yan Liao ◽

Yue Lin Zhang ◽

Aimin Xu ◽

Hung Fat Tse ◽

...

Keyword(s):

Area Under The Curve ◽

Treated Group ◽

Control Group ◽

Protective Effects ◽

Treatment Control ◽

Porcine Coronary Artery ◽

Endogenous Histamine ◽

Coronary Endothelium ◽

Treatment Control Group

In the porcine coronary artery, regenerated endothelium is dysfunctional as regards the responses to endothelium-dependent agonists. The current study aimed to determine the possible involvement of histamine in such dysfunction. Pigs were treated chronically with pyrilamine (H1 receptor inhibitor, 2 mg·kg−1·day−1) with part of their coronary endothelium and allowed to regenerate for 28 days after balloon denudation. The results showed a reduction in relaxation to bradykinin (Gq protein dependent) only in the pyrilamine-treated group (area under the curve, 269.7 ± 13.4 vs. 142.0 ± 31.0, native endothelium vs. regenerated endothelium) but not in the control group (253.0 ± 22.1 vs. 231.9 ± 29.5, native endothelium vs. regenerated endothelium). The differences in the relaxation to serotonin (Gi protein dependent) between native and regenerated endothelium were not affected by the pyrilamine treatment (control group, 106.3 ± 17.0 vs. 55.61 ± 12.7; and pyrilamine group, 106.0 ± 8.20 vs. 49.30 ± 6.31, native endothelium vs. regenerated endothelium). These findings indicate that during regeneration of the endothelium, the activation of H1 receptors by endogenous histamine may be required to maintain the endothelium-dependent Gq protein-mediated relaxation to bradykinin, suggesting a beneficial role of the monoamine in the process of endothelial regeneration.

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