scholarly journals Comparative study of vasodilatation after intra-arterial nicardipine or dantrolene infusion in animal model of cerebral vasospasm

2021 ◽  
Author(s):  
Jeongwook Lim ◽  
Young Dae Cho ◽  
Hyoung Soo Byoun
Keyword(s):  
Animal Model ◽  
Subarachnoid Hemorrhage ◽  
Drug Efficacy ◽  
Channel Blockers ◽  
Conventional Angiography ◽  
Duration Of Action ◽  
Vasodilatory Effect ◽  
New Zealand White Rabbits ◽  
Arterial Diameters

Abstract Intra-arterial (IA) infusions of calcium channel blockers (CCBs) have been widely applied in treating medically refractory vasospasm. However, surprisingly little is known regarding their vasodilatory duration. This study was undertaken to compare attributes of nicardipine and dantrolene, focusing on efficacy and capacity for sustained vasodilation. In New Zealand white rabbits (N=22), vasospasm was individually provoked through experimentally induced subarachnoid hemorrhage and confirmed via conventional angiography, grouping animals by IA-infused drug (nicardipine vs dantrolene). Controls received normal saline. After chemoangioplasty, follow-up angiography was performed at intervals of 1-3 hours for 6 hours to compare vasospastic and dilated (ie, treated) arterial diameters. Drug efficacy, duration of action, and changes in mean arterial pressure (relative to baseline) were analyzed by group. Compared with controls, effective vasodilation was evident in both nicardipine and dantrolene test groups after IA infusion. Vasodilatory effects of nicardipine peaked at 1 hour, returning to former vasospastic states at 3 hours. In dantrolene recipients, vasodilation endured longer, lasting >6 hours. This outcome suggests that IA dantrolene infused alone or together with a conventional CCB infusion may be a new means of prolonging vasodilatory effect. Further research is needed to assess durations of IA-infused vasodilatory drug based on perfusion status.

scholarly journals Systemic and CSF Interleukin-1α Expression in a Rabbit Closed Cranium Subarachnoid Hemorrhage Model: An Exploratory Study

2019 ◽  
Vol 9 (10) ◽  
pp. 249 ◽  
Author(s):  
Croci ◽  
Wanderer ◽  
Strange ◽  
Grüter ◽  
Casoni ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Sham Group ◽  
Delayed Cerebral Ischemia ◽  
Delayed Cerebral Vasospasm ◽  
Significant Difference ◽  
New Zealand White Rabbits ◽  
Interleukin 1Α ◽  
Correlation Trend

Background: The inflammatory pathway in cerebrospinal fluid (CSF) leads to delayed cerebral vasospasm (DCVS) and delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). The role of IL-1α has never been evaluated in a rabbit SAH model. The aim of our study is to analyze systemic and CSF changes of IL-1α, and to evaluate potential associations with the onset of DCVS in a rabbit closed cranium SAH model. Methods: 17 New Zealand white rabbits were randomized into two groups, SAH (n = 12) and sham (n = 5). In the first group, SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cerebral cistern of magna under intracranial pressure (ICP) monitoring. The sham group served as a control. The CSF and blood samples for IL-1α measurement were taken at day zero before SAH induction and at day three. Results: There was a significant increase of ICP (p = 0.00009) and a decrease of cerebral perfusion pressure (CPP) (p = 0.00089) during SAH induction. At follow up, there was a significant increase of systemic IL-1α in the SAH as compared with the sham group (p = 0.042). There was no statistically significant difference in the CSF values in both groups. The CSF IL-1α values showed a correlation trend of DCVS. Conclusions: Systemic IL-1α levels are elevated after SAH induction in a rabbit SAH model.

Optimal cerebrospinal fluid magnesium ion concentration for vasodilatory effect and duration after intracisternal injection of magnesium sulfate solution in a canine subarachnoid hemorrhage model

2011 ◽  
Vol 114 (4) ◽  
pp. 1168-1175 ◽  
Author(s):  
Kentaro Mori ◽  
Takuji Yamamoto ◽  
Masahiro Miyazaki ◽  
Yasukazu Hara ◽  
Yasuhisa Aiko ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Cerebral Arteries ◽  
Ion Concentration ◽  
Superior Cerebellar Artery ◽  
Arterial Diameter ◽  
Vasodilatory Effect ◽  
Intracisternal Injection ◽  
Arterial Diameters

Object The optimal CSF Mg++ concentration for vasodilation of spastic cerebral arteries after subarachnoid hemorrhage (SAH) and its duration are unknown. The temporal profile of the vasodilatory effect and optimal CSF Mg++ concentration after the intracisternal injection of MgSO4 solution were investigated in an SAH model in canines. Methods Cerebral vasospasm was induced by experimental SAH using a 2-hemorrhage model in 26 female beagles. On Day 7, 0.5 ml/kg of 15, 10, 5, or 0 mmol/L MgSO4 in Ringer solution was injected into the cerebellomedullary cistern. Angiography was performed on Day 1 (before SAH) and before and 1, 3, and 6 hours after the intracisternal injection on Day 7 to measure arterial diameters of the basilar artery (BA), superior cerebellar artery (SCA), and vertebral artery (VA). Cerebrospinal fluid Mg++ was also measured at the same time. Results Arterial diameters of the BA, SCA, and VA were significantly decreased by vasospasm on Day 7. Arterial diameter ratios (ratio of arterial diameter after MgSO4 injection to diameter before injection on Day 7) of the BA and SCA at 1 and 3 hours after and the VA at 1 hour after intracisternal injection of the MgSO4 solution were positively correlated with the CSF Mg++ concentration. All arterial diameter ratios, except 1 point of the SCA, exceeded 1 if the CSF Mg++ concentration was > 3 mEq/L at 1 hour after injection. Animals with CSF Mg++ concentrations > 3 mEq/L at 1 hour after injection (11 dogs) showed significantly increased arterial diameters of the BA at 1 and 3 hours after and of the SCA and VA at 1, 3, and 6 hours after injection, as compared with the diameters before injection. The CSF Mg++ concentration significantly increased at 1 hour (3.73 ± 0.69 mEq/L, p < 0.01) and 3 hours (2.05 ± 0.35 mEq/L, p < 0.01) after the intracisternal injection as compared with the baseline value (1.41 ± 0.20 mEq/L). Conclusions The reversible effect of an intracisternal injection of MgSO4 solution on the spastic artery requires CSF Mg++ concentrations > 3 mEq/L. The vasodilatory effect continues for 3–6 hours after injection. These results suggest that the continuous infusion or intermittent intracisternal injection of MgSO4 is needed to maintain the optimal CSF Mg++ concentration and constantly ameliorate cerebral vasospasm.

scholarly journals Evaluation of the Accero Stent for Stent-Assisted Coiling of Unruptured Wide-Necked Intracranial Aneurysm Treatment with Short-Term Follow-Up

2020 ◽  
Vol 9 (9) ◽  
pp. 2808
Author(s):  
Wojciech Poncyljusz ◽  
Kinga Kubiak ◽  
Leszek Sagan ◽  
Bartosz Limanówka ◽  
Katarzyna Kołaczyk
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intracranial Aneurysms ◽  
Clinical Results ◽  
Class I ◽  
Unruptured Aneurysms ◽  
Patient Demographics ◽  
Stent Deformation ◽  
Unruptured Intracranial Aneurysms ◽  
Occlusion Rate

Background: Stent-assisted coiling is an effective method of treating intracranial aneurysms. The aim of the study was to assess the safety and efficacy of the new Accero stent for the treatment of intracranial aneurysms. Materials and Methods: It was a retrospective, single-center study. Eighteen unruptured intracranial aneurysms were treated using the stent-assisted coiling method with the Accero stent. Patient demographics, aneurysm characteristics, procedural parameters, grade of occlusion, complications, and clinical results were analyzed. Follow-up magnetic resonance (MR) was performed 6 months after intervention. Results: Seventeen patients with 18 incidental unruptured aneurysms were electively treated with coiling and the Accero stent. The aneurysms were located on internal carotid artery (ICA), middle cerebral artery (MCA) and basilar artery (BA). All stents were deployed successfully. Immediate complete occlusion rate Raymond-Roy occlusion classification (RROC) class I was achieved in 13 cases and class II in 4 cases. Complications occurred in 2/17 treatments and included guidewire stent perforation with subarachnoid hemorrhage (SAH) and stent deformation. Vascular spasm in the subarachnoid hemorrhage (SAH) patient subsided before discharge. Ninety days after intervention, the modified Rankin Scale (mRS) value was 0. RROC class I was observed in 88.23% of cases in follow-up. Conclusion: The Accero stent provides excellent support for coil mass. It constitutes an efficacious device with good initial occlusion rate for treating wide-necked unruptured intracranial aneurysms.

scholarly journals A Novel Infection Protocol in Zebrafish Embryo to Assess Pseudomonas aeruginosa Virulence and Validate Efficacy of a Quorum Sensing Inhibitor In Vivo

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 401
Author(s):  
Pauline Nogaret ◽  
Fatima El El Garah ◽  
Anne-Béatrice Blanc-Potard
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Animal Model ◽  
Quorum Sensing ◽  
Drug Testing ◽  
Drug Efficacy ◽  
Embryo Viability ◽  
Immersion Method ◽  
Opportunistic Human Pathogen

The opportunistic human pathogen Pseudomonas aeruginosa is responsible for a variety of acute infections and is a major cause of mortality in chronically infected cystic fibrosis patients. Due to increased resistance to antibiotics, new therapeutic strategies against P. aeruginosa are urgently needed. In this context, we aimed to develop a simple vertebrate animal model to rapidly assess in vivo drug efficacy against P. aeruginosa. Zebrafish are increasingly considered for modeling human infections caused by bacterial pathogens, which are commonly microinjected in embryos. In the present study, we established a novel protocol for zebrafish infection by P. aeruginosa based on bath immersion in 96-well plates of tail-injured embryos. The immersion method, followed by a 48-hour survey of embryo viability, was first validated to assess the virulence of P. aeruginosa wild-type PAO1 and a known attenuated mutant. We then validated its relevance for antipseudomonal drug testing by first using a clinically used antibiotic, ciprofloxacin. Secondly, we used a novel quorum sensing (QS) inhibitory molecule, N-(2-pyrimidyl)butanamide (C11), the activity of which had been validated in vitro but not previously tested in any animal model. A significant protective effect of C11 was observed on infected embryos, supporting the ability of C11 to attenuate in vivo P. aeruginosa pathogenicity. In conclusion, we present here a new and reliable method to compare the virulence of P. aeruginosa strains in vivo and to rapidly assess the efficacy of clinically relevant drugs against P. aeruginosa, including new antivirulence compounds.

scholarly journals RNAi inhibition of angiopoietin-like protein 3 (ANGPTL3) with ARO-ANG3 mimics the lipid and lipoprotein profile of familial combined hypolipidemia

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G.F Watts ◽  
C Schwabe ◽  
R Scott ◽  
P Gladding ◽  
D Sullivan ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Response ◽  
Minimal Change ◽  
Funding Source ◽  
Private Company ◽  
Good Tolerability ◽  
Duration Of Action ◽  
Mixed Dyslipidemia ◽  
Genetic Deficiency

Abstract Background Elevated LDL-C and triglyceride rich lipoproteins (TRLs) are independent risk factors for cardiovascular disease (CVD). Genetic deficiency of angiopoietin-like protein 3 (ANGPTL3) is associated with reduced circulating levels of LDL-C, triglycerides (TGs), VLDL-C, HDL-C and reduced CVD risk, with no described adverse phenotype. ARO-ANG3 is a RNA interference drug designed to silence expression of ANGPTL3. Single doses of ARO-ANG3 have been shown to reduce ANGPTL3, TGs, VLDL-C and LDL-C in healthy volunteers (HVs, AHA 2019). We report the effects of multiple doses of ARO-ANG3 in HVs with a focus on the duration of action. Methods ARO-ANG3 was administered subcutaneously to HVs on days 1 and 29 at doses of 100, 200 or 300 mg (n=4 per group). Measured parameters included ANGPTL3, LDL-C, TGs, VLDL-C and HDL-C. Follow up is ongoing. Results All HVs have received both doses and follow-up is currently through week 16 (12 weeks after second dose). Mean nadir for ANGPTL3 levels occurred 2 weeks after the second dose (−83–93%) with minimal change for 200 and 300 mg but 16% recovery for 100 mg at week 16. Mean TGs and VLDL-C reached nadir earlier (3 wks, −61–65%) without apparent dose response and minimal change for any dose at wk 16. LDL-C nadir occurred 4–6 wks after the second dose (−45–54%), again with minimal evidence for dose response or change through wk 16. HDL-C was reduced 14–37% at wk 16. ARO-ANG3 was well tolerated without serious or severe adverse events or dropouts related to drug. The most common adverse events have been headache and upper respiratory infections. Conclusions Genetic deficiency of ANGPTL3 is a cause of familial combined hypolipemia and is associated with a decreased risk of CVD. Using RNAi to selectively suppress ANGPTL3 production reproduces these genetic effects with a duration of at least 12 weeks following a second dose and with good tolerability over 16 wks. ANGPTL3 inhibition results in lowering of LDL-C and TRLs which may confer protection against CVD in patients with atherogenic mixed dyslipidemia. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Arrowhead Pharmaceuticals

scholarly journals Aspirin treatment prevents inflammation in experimental bifurcation aneurysms in New Zealand White rabbits

2021 ◽  
pp. neurintsurg-2020-017261
Author(s):  
Stefan Wanderer ◽  
Basil Erwin Grüter ◽  
Fabio Strange ◽  
Gwendoline Boillat ◽  
Sivani Sivanrupan ◽  
...  
Keyword(s):  
New Zealand ◽  
Clinical Situation ◽  
Fluorescence Angiography ◽  
Preventive Effect ◽  
Aneurysm Formation ◽  
Aneurysm Wall ◽  
New Zealand White Rabbits ◽  
Aneurysm Thrombosis ◽  
Wall Groups

BackgroundAneurysm wall degeneration is linked to growth and rupture. To address the effect of aspirin (ASA) on aneurysm formation under various wall conditions, this issue was analyzed in a novel rabbit bifurcation model.MethodsBifurcation aneurysms created in 45 New Zealand White rabbits were randomized to vital (n=15), decellularized (n=13), or elastase-degraded (n=17) wall groups; each group was assigned to a study arm with or without ASA. At follow-up 28 days later, aneurysms were evaluated for patency, growth, and wall inflammation at macroscopic and histological levels.Results36 rabbits survived to follow-up at the end of the trial. None of the aneurysms had ruptured. Patency was visualized in all aneurysms by intraoperative fluorescence angiography and confirmed in 33 (92%) of 36 aneurysms by MRI/MRA. Aneurysm size was significantly increased in the vital (without ASA) and elastase-degraded (with and without ASA) groups. Aneurysm thrombosis was considered complete in three (50%) of six decellularized aneurysms without ASA by MRI/MRA. Locoregional inflammation of the aneurysm complex was significantly reduced in histological analysis among all groups treated with ASA.ConclusionASA intake prevented inflammation of both the periadventitial tissue and aneurysm wall, irrespective of initial wall condition. Although ASA prevented significant growth in aneurysms with vital walls, this preventive effect did not have an important role in elastase-degraded pouches. In possible translation to the clinical situation, ASA might exert a potential preventive effect during early phases of aneurysm formation in patients with healthy vessels but not in those with highly degenerative aneurysm walls.

scholarly journals Pulmonary arteriovenous malformation (PAVM) embolization: prediction of angiographically-confirmed recanalization according to PAVM Diameter changes on CT

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jihoon Hong ◽  
Sang Yub Lee ◽  
Jung Guen Cha ◽  
Jae-Kwang Lim ◽  
Jongmin Park ◽  
...  
Keyword(s):  
Arteriovenous Malformation ◽  
Case Series ◽  
Pulmonary Angiography ◽  
Endovascular Embolization ◽  
Pulmonary Arteriovenous Malformation ◽  
Conventional Angiography ◽  
Receiver Operating Characteristic Curves ◽  
Vein Diameter ◽  
Diameter Reduction

Abstract Background To assess pulmonary arteriovenous malformation (PAVM) recanalization after embolization based on PAVM diameter changes on computed tomography (CT), with pulmonary angiography used as a gold standard. Methods A retrospective review was done of patients from 2008 to 2019 with a PAVM treated with endovascular embolization. The treatment outcome was determined by conventional angiography. Follow-up pulmonary angiography was performed when recanalization was suspected on CT, or embolization of all lesions in multiple PAVM patients could not be completed in a single session. Patients who had no preprocedural or follow-up CT were excluded. Draining vein, feeding artery, and venous sac diameter were measured on CT, and diameter reduction rates were compared with the widely-used, binary 70 % criteria. Results Forty-one patients with 114 PAVMs were treated during the study period. Eight patients with 50 PAVMs met the inclusion criteria. Mean vein, artery, and venous sac diameter reduction rates were as follows: 59.2 ± 9.3 %, 47.5 ± 10.6 %, and 62.6 ± 13.2 %, respectively, in the occluded group and 5.4 ± 19.5 %, 11.3 ± 17.7 %, and 26.8 ± 14.2 %, respectively, in the recanalized group. The area under the receiver operating characteristic curves for PAVM recanalization for the draining vein was 1.00, showing a better result than the artery (0.97) and sac (0.99). Patients showed > 42 % draining vein diameter reduction in the occluded group and < 32 % in the recanalized group. The widely-used 70 % criteria showed low specificity for predicting recanalization (draining vein, 7.3 %; venous sac, 41.7 %) but 100 % sensitivity for both the draining vein and venous sac. Conclusions The widely-used 70 % binary criteria showed limited performance in predicting outcomes in this angiographically-confirmed case series. Further investigations are warranted to establish a strategy for detecting recanalization after PAVM embolization.

Association of Refractory Pain in the Acute Phase After Subarachnoid Hemorrhage with Continued Outpatient Opioid Use

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011906
Author(s):  
Matthew N. Jaffa ◽  
Jamie E. Podell ◽  
Madeleine C. Smith ◽  
Arshom Foroutan ◽  
Adam Kardon ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Ethnic Minority ◽  
Acute Phase ◽  
Acute Illness ◽  
Minority Status ◽  
Opioid Use ◽  
Opioid Dose ◽  
Refractory Pain ◽  
Racial Ethnic

ObjectiveLittle is known about the prevalence of continued opioid use following aneurysmal subarachnoid hemorrhage (aSAH) despite guidelines recommending their use during the acute phase of disease. We sought to determine prevalence of opioid use following aSAH and test the hypothesis that acute pain and higher inpatient opioid dose increased outpatient opioid use.MethodsWe reviewed consecutively admitted aSAH patients from November 2015 through September 2019. We retrospectively collected pain scores and daily doses of analgesics. Pain burden was calculated as area under the pain-time curve. Univariate and multivariable regression models determined risk factors for continued opioid use at discharge and outpatient follow-up.ResultsWe identified 234 aSAH patients with outpatient follow-up. Continued opioid use was common at discharge (55% of patients) and follow-up (47% of patients, median 63 (IQR 49–96) days from admission). Pain burden, craniotomy, and racial-ethnic minority status were associated with discharge opioid prescription in multivariable analysis. At outpatient follow-up, pain burden (OR 1.88, 95% CI 1.5–2.4), depression (OR 3.1, 95% CI 1.1–8.8), and racial-ethnic minority status (OR 2.1, 95% CI 1.1–4.0) were independently associated with continued opioid use while inpatient opioid dose was not.ConclusionContinued opioid use following aSAH is prevalent and related to refractory pain during acute illness, but not inpatient opioid dose. More efficacious analgesic strategies are needed to reduce continued opioid use in patients following aSAH.Classification of evidenceThis study provides Class II evidence that continued opioid use following aSAH is associated with refractory pain during acute illness but not hospital opioid exposure.

Comparison of Cefpodoxime Proxetil and Cefixime in the Treatment of Acute Otitis Media in Infants and Children

PEDIATRICS ◽  
1994 ◽  
Vol 94 (6) ◽  
pp. 847-852
Author(s):  
Basim I. Asmar ◽  
Adnan S. Dajani ◽  
Mark A. Del Beccaro ◽  
Paul M. Mendelman ◽  
Keyword(s):  
Otitis Media ◽  
Acute Otitis Media ◽  
Drug Efficacy ◽  
Oral Suspension ◽  
Suppurative Otitis Media ◽  
Once Daily ◽  
Cefpodoxime Proxetil ◽  
Long Term Follow Up ◽  
Cure Rates

Objective. To compare the use of once-a-day cefpodoxime proxetil to once-a-day cefixime in the treatment of acute suppurative otitis media. Design. Randomized, multicenter, investigator-blinded. Setting. Outpatient. Patients. A total of 368 patients (age 2 months to 17 years) were randomized to receive either cefpodoxime or cefixime in a 2:1 ratio (245 cefpodoxime, 123 cefixime); 236 patients (155 cefpodoxime, 81 cefixime) were evaluable for drug efficacy. Interventions. Patients received either cefpodoxime proxetil oral suspension (10 mg/kg/day, once daily for 10 days) or cefixime oral suspension (8 mg/kg/day, once daily for 10 days). Main outcome measures. Clinical evaluations were performed before treatment (study day 1), at an interim visit (study day 3 through 6), at the end of therapy (study day 12 through 15), and at final follow-up (study day 25 through 38). Microbiologic evaluations were performed at enrollment and whenever appropriate thereafter. Results. End-of-therapy clinical cure rates in evaluable patients were 56% for the cefpodoxime group and 54% for the cefixime group. Clinical improvement rates were 27% for both groups. Clinical response rates were not significantly different between treatment groups (P = .541; 95% confidence interval = -8.1%, 15.2%). At long-term follow-up, 17% of patients in the cefpodoxime group and 20% in the cefixime group had a recurrence of infection. Drug-related adverse events (eg, diarrhea, diaper rash, vomiting, rash) occurred in 23.3% of cefpodoxime-treated patients and 17.9% of cefixime-treated patients (P = .282). Conclusions. These findings suggest that cefpo-doxime proxetil administered once daily is as effective and safe as cefixime given once daily in the treatment of acute suppurative otitis media in pediatric patients.

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