Intra-arterial Administration Research Articles

Dietary restriction for prevention of contrast-induced acute kidney injury in patients undergoing percutaneous coronary angiography: a randomized controlled trial

Short-term dietary restriction (DR) may prevent organ damage from ischemic or toxic insults in animals, but clear evidence in humans is missing. While especially intraarterial administration of contrast media represents a cause of hospital-acquired acute kidney injury (AKI), targeted preventive strategies are not available. This trial investigated the feasibility and effectiveness of pre-interventional DR for preventing AKI in patients undergoing percutaneous coronary intervention (PCI). Patients were randomized to receive a formula diet containing 60% of daily energy requirement (DR group) or ad-libitum food during the 4-day-interval before PCI. Primary endpoint was change of serum creatinine 48 h after PCI (Δcreatinine). Further analyses included incidence of AKI and safety evaluation. Δcreatinine post PCI in the DR group vs. the control group did not show any difference (DR: 0.03(−0.15,0.14)mg/dL vs. control: 0.09(−0.03,0.22)mg/dL;p = 0.797). Subgroup analyses revealed a significant beneficial impact of DR in patients that received ≤100 ml of contrast agent (DR n = 26: Δcreatinine −0.03(−0.20,0.08)mg/dL vs. control n = 24: Δcreatinine 0.10(−0.08,0.24)mg/dL; p = 0.041) and in patients with ≤2 risk factors for AKI (DR: n = 27; Δcreatinine −0.01(−0.18,0.07)mg/dL vs. control n = 31: Δcreatinine 0.09(−0.03,0.16)mg/dl; p = 0.030). Although the primary endpoint was not met, the results of this trial suggest a beneficial impact of DR in low-to-moderate risk patients.

Severe Periocular Edema after Intraarterial Carboplatin Chemotherapy for Retinoblastoma in a Rabbit (Oryctolagus cuniculus) Model

Endovascular microcatheter-based intraarterial (ophthalmic artery) chemotherapy is becoming widely used for the clinical treatment of intraocular retinoblastoma due to its apparent increased efficacy compared with traditional intravenous chemotherapy; however local ocular complications are not uncommon. Carboplatin is a chemotherapeutic agent used in both intravenous and intraarterial chemotherapy. We used rabbits to assess pharmacokinetics and ocular and systemic toxicity after intraarterial carboplatin infusion. Subsequent to unilateral intraarterial administration of carboplatin, severe unilateral or bilateral periocular edema occurred in 6 adult male New Zealand white rabbits. Time to onset varied from less than 4 h after administration (n = 3, 50 mg) to approximately 24 h afterward (n = 3, 25 mg). After becoming symptomatic, 5 of the 6 animals were promptly euthanized, and the remaining animal (25 mg treatment) was medically managed for 4 d before being euthanized due to intractable edema-related lagophthalmos. Globes and orbits from all 6 euthanized rabbits were harvested en bloc; whole-mount sections were prepared for histologic evaluation, which revealed drug-induced vasogenic edema in confined spaces as the main underlying pathogenesis. Transient and self-limiting periocular edema is a common side effect of intraarterial chemotherapy but is thought to occur predominantly with melphalan monotherapy or combination therapy using melphalan, carboplatin, and topotecan. The severity of this adverse consequence in rabbits was unexpected, and its use in the study was subsequently discontinued. Although the definitive cause for this vasotoxicity and striking clinical presentation is unknown, we suspect species-specific anatomic features and sensitivity might have contributed to amplified complications after intraarterial carboplatin chemotherapy of the eye. Due to the adverse effects of intraarterial carboplatin chemotherapy that we observed in 2 experimental cohorts of rabbits, we recommend caution regarding its use in this species.

3:00 PM Abstract No. 182 Effect of intra-arterial nitroglycerin and verapamil administration during radial artery access on systemic blood pressure and its correlation with timing of moderate sedation administration

3:00 PM Abstract No. 182 Effect of intra-arterial nitroglycerin and verapamil administration during radial artery access on systemic blood pressure and its correlation with timing of moderate sedation administration

Intra-arterial lidocaine administration during uterine fibroid embolization to reduce the immediate postoperative pain: a prospective randomized study

BackgroundTo investigate if intra-arterial lidocaine administrated immediately after the embolisation endpoint reduces the pain.MethodsForty patients were randomised and 36 completed the study for purposes of analysis. In one group, the patients got 1% 10 ml lidocaine (100 mg) administered into each uterine artery immediately after embolisation with microspheres. The other group was embolised without supplementary lidocaine. The patients scored their pain on a visual analogue scale (VAS) 2 h, 4 h, 7 h, 10 h and 24 h after embolisation, and the total amount of used morphine was noted. Three-month follow-up MRI control was scheduled for all the patients to investigate the infarction rate.ResultsEmbolisation was performed without any complications and with embolisation of both uterine arteries in all cases. Intra-arterial lidocaine was administered in all 20 patients without complications, and 20 patients in a control group did not receive lidocaine intra-arterial. VAS schemes showed a significant reduction in pain experience 2 h after UFE where mean pain score in the lidocaine group was 42.7 ± 21.4 compared with the control group in which the mean pain score was 61.1 ± 20.4 (p < 0.02). There was no significant difference in pain score 4 h, 7 h, 10 h and 24 h after UFE. In the lidocaine group, the mean amount of used morphine was significantly less with 11.2 mg compared with 20.2 mg in the control group (p < 0.03). Three months of MR follow-up control showed no significant difference in the grade of fibroid infarction.ConclusionIntra-arterial Lidocaine administration after embolisation is safe and effective in reducing post-procedural pain in the early hours and opioid usage in the first 24 h following UAE.

Adenovirus-Antibody Complexes Contributed to Lethal Systemic Inflammation in a Gene Therapy Trial

Intra-arterial administration of an adenovirus serotype 5 (Ad5) vector in a gene therapy trial caused lethal, systemic inflammation in subject 019 with ornithine transcarbamylase deficiency. This unanticipated inflammatory response was absent in another subject receiving the same vector dose and in 16 subjects receiving lower vector doses. We hypothesized that an immune memory to a previous natural adenovirus infection enhanced the immune response to high-dose systemic Ad5 vector,causing the exaggerated immune response in subject 019. To investigate this, we found that rabbit polyclonal sera to Ad5 and pooled human immunoglobulin (Ig) inhibited Ad5 vector transduction of non-immune cells invitro, but enhanced transduction and activation of human dendritic cells(DCs). Sera from approximately 7% of normal human subjects and 50% of patients treated topically with Ad5 vectors enhanced Ad5 transduction and activation of DCs, apparently from formation of Ig-Ad5 immune complexes and binding to DCs through FcγR. Subject 019's blood substantially increased Ad5-vector activation of human DC primary cultures at levels exceeding those from normal subjects. Although this study is based on one event in a single subject, the results implicatea pre-existing humoral immune response to Ad5 in the lethal systemic inflammatory response that occurred in subject019.

Intra-arterial versus standard intravenous administration of lutetium-177-DOTA-octreotate in patients with NET liver metastases: study protocol for a multicenter, randomized controlled trial (LUTIA trial)

BackgroundLutetium-177-DOTA-octreotate (177Lu-DOTATATE) significantly increases survival and response rates in patients with grade I and grade II neuroendocrine tumors (NETs). However, survival and response rates are significantly lower in patients with bulky liver metastases. Increasing the tumor-absorbed dose in liver metastases may improve response to 177Lu-DOTATATE. The LUTIA (Lutetium Intra-Arterial) study aims to increase the tumor-absorbed dose in liver metastases by intra-arterial (IA) administration of 177Lu-DOTATATE, compared to conventional intravenous (IV) administration.MethodsA multicenter, within-patient randomized controlled trial (RCT) in 26 patients with progressive, liver-dominant, unresectable grade I or grade II NET will be conducted. Patients with bilobar bulky disease will be randomly allocated to receive IA treatment into either the left or the right hepatic artery. Using this approach, one liver lobe will be treated intra-arterially (first-pass effect), while the contralateral lobe will receive an intravenous treatment as a second-pass effect. The primary endpoint of this study is the difference in tumor-to-non-tumor ratio of 177Lu-DOTATATE uptake between the two liver lobes on post-treatment SPECT/CT (IA versus IV). Secondary endpoints include absorbed dose in both liver lobes, tumor response, dose-response relationship, toxicity, uptake in extrahepatic lesions, and renal uptake.DiscussionThis multicenter, within-patient RCT will investigate whether IA administration of 177Lu-DOTATATE results in a higher activity concentration in liver metastases compared to IV administration.Trial registrationClinicalTrials.gov, NCT03590119. Registered on 17 July 2018.

Renovascular hypertension elevates pulmonary ventilation in rats by carotid body-dependent mechanisms.

The two kidney-one clip (2K1C) renovascular hypertension depends on the renin-angiotensin system and sympathetic overactivity. The maintenance of 2K1C hypertension also depends on inputs from the carotid bodies (CB), which when activated stimulate the respiratory activity. In the present study, we investigated the importance of CB afferent activity for the ventilatory responses in 2K1C hypertensive rats and for phrenic and hypoglossal activities in in situ preparations of normotensive rats treated with angiotensin II. Silver clips were implanted around the left renal artery of male Holtzman rats (150 g) to induce renovascular hypertension. Six weeks after clipping, hypertensive 2K1C rats showed, in conscious state, elevated resting tidal volume and minute ventilation compared with the normotensive group. 2K1C rats also presented arterial alkalosis, urinary acidification, and amplified hypoxic ventilatory response. Carotid body removal (CBR), 2 wk before the experiments (4th week after clipping), significantly reduced arterial pressure and pulmonary ventilation in 2K1C rats but not in normotensive rats. Intra-arterial administration of angiotensin II in the in situ preparation of normotensive rats increased phrenic and hypoglossal activities, responses that were also reduced after CBR. Results show that renovascular hypertensive rats exhibit increased resting ventilation that depends on CB inputs. Similarly, angiotensin II increases phrenic and hypoglossal activities in in situ preparations of normotensive rats, responses that also depend on CB inputs. Results suggest that mechanisms that depend on CB inputs in renovascular hypertensive rats or during angiotensin II administration in normotensive animals increase respiratory drive.

Antibacterial and Antifungal Therapy for Patients with Acute Pancreatitis at High Risk of Pancreatogenic Sepsis (Review).

Controlling infection is crucial in treating patients with acute pancreatitis (AP). The infectious process in AP often predisposes to subsequent sepsis by damaging not only the pancreas, but retroperitoneal tissues as well. Among other AP-associated factors, are the rapidly developing immune imbalance, the poor penetration of antimicrobial agents into necrotic tissue, and the impossibility of a single surgical debridement. Antibacterial and antifungal therapy for patients with infected necrosis and AP-associated extra-pancreatic infections remains a complex and largely unresolved problem, partially due to the high occurrence of multiresistant pathogens. The preventive use of antimicrobial agents has been discussed in the literature; however, the lack of consistent results makes it difficult to develop a unified strategy and clinical guidelines on this specific issue. Recent meta-analyses provide no conclusive evidence that antibacterial prophylaxis reduces the infection rate, mortality, or the need for surgical treatment in patients with necrotizing pancreatitis. We found only two studies indicating the benefits of using carbapenems for prophylactic purposes and one meta-analysis indicating a reduction in mortality under antibiotic treatment started no later than 72 h after the onset of the attack. Selective bowel decontamination is considered as one of the preventive anti-infection measures, although the available data may not be fully reliable.The main indications for antibacterial therapy in patients with AP are confirmed infected necrosis or extra-pancreatic infection, as well as clinical symptoms of suspected infection. Intra-arterial administration or local treatment with antibiotics can increase the efficacy of antibacterial therapy. No randomized studies on antifungal prophylaxis in AP are available; some reports though recommend using such therapy among patients at high risk of invasive candidiasis.

Endovascular Pressure Measurements to Assess the Functional Severity of Mesenteric Arterial Stenoses.

To assess the ability of pressure measurements to discriminate clinically significant celiac artery (CA) or superior mesenteric artery (SMA) stenosis in patients with suspected chronic mesenteric ischemia (CMI). Single-center, retrospective cohort study of 41 intra-arterial pressure measurements during mesenteric angiography with intended revascularization, performed in 37 patients (mean age 67.7 ± 10.8 years, 62% female) between April 2015 and May 2017. Simultaneous prestenotic and poststenotic pressure measurements had been obtained before and after intra-arterial administration of nitroglycerin. Revascularization was performed in 38 of 41 procedures. Definitive diagnosis of CMI was defined as patient-reported symptom relief or improvement after successful revascularization. Pressure gradients obtained after vasodilator administration were significantly higher in CAs and SMAs with ≥50% stenosis. Pressure ratios (pressure distal [Pd]/pressure aorta [Pa]) obtained after vasodilator administration were significantly higher in CAs with ≥50% stenosis. Subgroup analysis of 22 patients with a ≥50% stenosis of either CA or SMA showed significantly higher pressure gradients and Pd/Pa ratios after vasodilator administration in CMI patients (median pressure gradient: CMI [interquartile ratio] 36 [21-40] mm Hg versus no-CMI 20 [9-21] mm Hg, P= 0.041; Pd/Pa: CMI 0.703 [0.598-0.769] versus no-CMI 0.827 [0.818-0.906], P= .009). A ≤0.8 Pd/Pa cutoff value after administration of a vasodilator best identified a clinically relevant stenosis, with 86% sensitivity and 83% specificity. Complications related to the pressure measurements were not observed. Intra-arterial pressure measurements are feasible and safe. Low Pd/Pa ratios were associated with clinically relevant CA or SMA stenosis.

Tirofiban for acute ischemic stroke: systematic review and meta-analysis.

The safety and efficacy of tirofiban for patients with acute ischemic stroke (AIS) remains controversial. We therefore conducted a systematic review and meta-analysis. We searched PubMed, EMBASE, Cochrane Library, Web of Science, and related international clinical trials registries through March 31, 2019, using the terms "tirofiban" and "stroke". All apparently unconfounded randomized controlled trials (RCTs) and cohort studies with two arms comparing treatment with and without tirofiban for AIS were included in this review. Primary outcomes included symptomatic intracranial hemorrhage (sICH), fatal ICH, mortality, and modified Rankin Scale (mRS 0-2) at 3months. Seventeen studies including 2914 AIS patients were identified. Pooled results showed that tirofiban treatment in AIS did not increase the risk of sICH (OR, 0.95; 95% CI, 0.71-1.28; p = 0.75) or mortality (OR, 0.80; 95% CI; 0.64-1.02; p = 0.07). However, fatal ICH increased significantly in the tirofiban treatment group (OR, 2.84; 95% CI, 1.38-5.85; p = 0.005), and subgroup analysis showed that tirofiban via intra-arterial (IA) administration was associated with increased risk of fatal ICH (OR, 2.90; 95% CI, 1.12-7.55; p = 0.03), while intravenous (IV) administration was not (OR, 2.75; 95% CI, 0.92-8.20; p = 0.07). In addition, tirofiban showed no obvious improvement in functional outcome (mRS 0-2) (OR, 1.29; 95% CI, 0.97-1.71; p = 0.08). Tirofiban seems to be safe in systemic treatment and may represent a potential choice for management of AIS. However, intra-arterial administration requires further adequately controlled studies in order to develop an appropriate protocol, similar to that in cardiology.

Subclinical Contrast-Induced Acute Kidney Injury in Patients Undergoing Cerebral Computed Tomography

Introduction: The nephrotoxicity of modern contrast media remains controversial. Novel biomarkers of kidney damage may help in identifying a subclinical structural renal injury not revealed by widely used markers of kidney function. Objective: The aim of this study was to investigate clinical (contrast-induced acute kidney injury [CI-AKI]) and subclinical CI-AKI (SCI-AKI) after intra-arterial administration of Iodixanol and Iopamidol in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m². Methods: This is a prospective observational monocentric study. Urinary sample was collected at 4–8 h after contrast medium exposure to measure neutrophil gelatinase associated lipocalin (NGAL) and the product tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), while blood samples were collected at 24 and 48 h after exposure to measure serum creatinine. Results: One hundred patients were enrolled, of whom 53 were exposed to Iodixanol and 47 to Iopamidol. Patients in Iodixanol and Iopamidol groups were comparable in terms of demographics, pre-procedural and procedural data. No patient developed CI-AKI according KDIGO criteria, while 13 patients reported SCI-AKI after exposure to iodine-based medium contrast (3 patients in Iodixanol group and 10 patients in Iopamidol group), defined by positive results of NGAL and/or [TIMP-2] × [IGFBP7]. A positive correlation was found between NGAL and [TIMP-2] × [IGFBP7] in the analysed population (Spearman’s rho 0.49, p < 0.001). In logistic regression analysis, Iopamidol exposure showed higher risk for SCI-AKI compared to Iodixanol (OR 4.5 [95% CI 1.16–17.52], p = 0.030), even after controlling for eGFR and volume of contrast medium used. Conclusions: This study showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease. Further investigations on larger scale are warranted to confirm if Iopamidol exposed patients to increased risk of SCI-AKI compared to Iodixanol.

Intra-Arterial Lidocaine Is Not Found to Be Effective for Reducing Pain after Uterine Fibroid Embolization in a Retrospective Study: Now What?

I would like to thank the authors for undertaking and publishing the study titled “Intra-arterial lidocaine administration for anesthesia after uterine artery embolization with trisacryl gelatin microspheres for leiomyoma.” With uterine artery embolization (UAE) for fibroids being a frequently performed interventional radiology procedure in many practice settings, the subject matter is undoubtedly relevant to Journal of Vascular and Interventional Radiology readers. Also, there is limited understanding of the mechanism in question—that is, the way in which intra-arterial lidocaine can reduce pain in an embolized uterine artery.

Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review

ObjectiveTo systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage.MethodsThe Pubmed®, Cochrane and Embase databases were screened for articles published from April 2001 to February 2019. Two independent reviewers performed the methodological quality screening and data extraction of the studies.ResultsTwenty-two studies were found to be relevant, and only one of these was a randomized control trial. Studies showed marked heterogeneity and weaknesses in key methodological criteria. Most patients presented with moderate to severe vasospasm. Angiography was the main method of diagnosing vasospasm. Intra-arterial administration of milrinone was performed in three studies, intravenous administration was performed in nine studies, and both routes of administration in six studies; the intrathecal route was used in two studies, the cisternal route in one study and endovascular administration in one study. The side effects of milrinone were described in six studies. Twenty-one studies indicated resolution of vasospasm.ConclusionThe current evidence indicates that milrinone may have a role in treatment of vasospasm after aneurysmal subarachnoid hemorrhage. However, only one randomized control trial was performed, with a low quality level. Our findings indicate the need for future randomized control trials with patient-centered outcomes to provide definitive recommendations.

Сердечная недостаточность и контрастиндуцированное острое повреждение почек у больных с ишемической болезнью сердца

Aim. To assess the influence of heart failure on the risk of contrast-induced acute kidney injury (CI-AKI) in patients with stable coronary artery disease (CAD) with indications to diagnostic procedures requiring intra-arterial administration of contrast media. Materials and methods. 1023 patients, who were receiving optimal medical therapy and had indications to coronary angiography and possible coronary angio-plasty, with stable CAD were included in the study. We conducted an observational open prospective cohort study, which was registered in clinicaltrials.gov with ID NCT04014153. CI-AKI was defined as 25% or more increase of baseline serum creatinine, or more than 0.5 mg/dl and was assessed 48 hours after contrast media administration. The primary endpoint was the CI-AKI development according to KDIGO criteria. Most of the patients, included in the study, were males aged 66.3±10 years with arterial hypertension and overweight (BMI 29.14±5 kg/m2). Results. The study included 1023 patients, 76 suffered from heart failure. The rate of CI-AKI in this group was 13.2% (10 patients). The rate of CI-AKI using the absolute creatinine rise definition was 4% cases (3 cases). Conclusion. Female patients suffering from heart failure with higher levels of serum creatinine and low glomerular filtration rate need more attention, less amount of contrast and adequate preventive measures before contrast media administration in order to lower the risk of CI-AKI development.

Neurogenin-1 Overexpression Increases the Therapeutic Effects of Mesenchymal Stem Cells through Enhanced Engraftment in an Ischemic Rat Brain.

Background and ObjectivesStem cell therapy is a promising strategy for treating neurological diseases but its effectiveness is influenced by the route of administration and the characteristics of the stem cells. We determined whether neural induction of mesenchymal stem cells (MSCs) was beneficial when the cells were delivered intra-arterially through the carotid artery.Methods and ResultsMSCs were neurally induced using a retroviral vector expressing the neurogenic transcription factor neurogenin-1 (Ngn1). The LacZ gene encoding bacterial β-galactosidase was used as a control. Ischemic stroke was induced by transluminal occlusion of the middle cerebral artery and 3 days later the MSCs were delivered intra-arterially through the internal carotid artery. Magnetic resonance imaging analysis indicated that compared to MSCs expressing LacZ (MSCs/LacZ), MSCs expressing Ngn1 (MSCs/Ngn1) exhibited increased recruitment to the ischemic region and populated this area for a longer duration. Immunohistochemical analysis indicated that compared to MSCs/LacZ, MSCs/Ngn1 more effectively alleviated neurological dysfunction by blocking secondary damage associated with neuronal cell death and brain inflammation. Microarray and real-time PCR analysis indicated that MSCs/Ngn1 exhibited increased expression of chemotactic cytokine receptors, adherence to endothelial cells, and migration ability.ConclusionsNeural induction with Ngn1 increases the homing ability of MSCs, enhancing their engraftment efficiency in the ischemic rat brain. Intra-arterial delivery of neurally induced MSCs/Ngn1 3 days after ischemic injury blocks neuronal cell death and inflammation, and improves functional recovery. Thus, intra-arterial administration of stem cells with neural properties may be a novel therapy for the treatment of ischemic stroke.

An Observational study about the levels of bifurcationsin Common Carotid Artery among male &amp; female cadavers

Introduction: The carotid arterial system which begins from the common carotid arteries (CCAs) is the main arterial supply of the head and neck. The knowledge of point of bifurcation of CCA is very important in surgeries of head and neck region to prevent vascular accidents, during catheterization of carotid arteries and intra-arterial administration of chemotherapeutic agents. The carotid arteries lying anterolaterally in the neck are the major structures commonly injured in penetrating wounds of the neck Hence this study to evaluate the variations, levels of divisions among both male and female cadavers in Local Medical Teaching Institutes. Methods: This Observational based descriptive study design was conducted to describe the CCA bifurcation. Study was undertaken in 30 adult formalin fixed cadavers The dissections were carried out according to the instructions given in Cunningham’s manual of practical anatomy . The level of bifurcation of common carotid artery was noted and correlated with the upper border of thyroid cartilage. The age of death ranged from 24 to 78 years and all specimens were fixed in 10% formaldehyde solution. Result: A total of thirty unclaimed adult cadavers of 3 females and 27 males or 60 specimens (30 cadavers, left and right sides). The height of cadavers ranges from 154 cm – 180 cm.The level of bifurcation of the common carotid artery was at the level of upper border of thyroid cartilage in 78.33%. Only 11.66%) showed the higher level . 10 % showed the lower level of bifurcation in the range of 2 mm to 10 mm below the level of upper border of thyroid cartilage. The bifurcation levels were symmetrical on both sides. Conclusion: The present study finds the incidence of bifurcation of common carotid was more or less constant at the level of upper border of thyroid cartilage. Clinicians / Surgeons need to take the standard and variable heights of the carotid bifurcation into consideration; to avoid unnecessary complications.

Intra-Arterial Lidocaine Administration for Anesthesia after Uterine Artery Embolization with Trisacryl Gelatin Microspheres for Leiomyoma.

To evaluate whether administration of lidocaine into the uterine artery for anesthesia immediately after uterine artery embolization (UAE) with trisacryl gelatin microspheres (TAGM) for leiomyoma is safe and effective. In a single-institution retrospective study, 100 patients underwent UAE using TAGM with a pruned tree endpoint between June 2014 and April 2019. The first 50 patients (control group) underwent UAE without lidocaine; in the second 50 patients (study group), lidocaine was administered into the uterine artery immediately after UAE. Baseline characteristics and technical and periprocedural outcomes were compared. Visual analog scale (VAS) scores 0, 3, 6, 9, 12, and 18 hours after UAE were compared between the groups with repeated measures analysis of variance. Each multivariate-adjusted VAS score < 24 hours was compared with analysis of covariance. No significant differences were observed in baseline characteristics or technical and periprocedural outcomes, including the volume of morphine used (P= .415), between the groups. No significant differences were found in crude or multivariate-adjusted VAS scores at each time point < 24 hours. Only the multivariate-adjusted VAS score 3 hours after UAE was 0.7 lower in the study group (mean ± SE, 2.2 ± 0.3 vs 2.9 ± 0.3); however, no significant difference was noted (P= .070). No adverse events associated with lidocaine were detected. Intra-arterial lidocaine administration immediately after UAE with TAGM for leiomyoma was safe, but did not contribute to significant reductions in pain or volume of narcotic agent administered.

Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke

BackgroundStroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et al., J Cereb Blood Flow Metab 37:3531–3543, 2017; Hill et al., Lancet Neurol 11:942–950, 2012; Amaro et al., Stroke 47:2874–2876, 2016).MethodsTransient stroke was induced in mice via one of two methods. One group of mice were subjected to tandem ipsilateral common carotid artery and middle cerebral artery occlusion, while another group underwent the filament-based middle cerebral artery occlusion. We have recently developed an animal model of intra-arterial (IA) drug administration after recanalization (Maniskas et al., J Neurosci Met 240:22–27, 2015). Sub groups of the mice were treated with either saline or Il-1α, wherein the drug was administered either acutely (immediately after surgery) or subacutely (on the third day after stroke). This was followed by behavioral and histological analyses.ResultsWe now show in the above-mentioned mouse stroke models (transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery occlusion (MCA) occlusion, MCA suture occlusion) that IL-1α is neuroprotective when acutely given either intravenously (IV) or IA at low sub-pathologic doses. Furthermore, while IV administration induces transient hemodynamic side effects without affecting systemic markers of inflammation, IA delivery further improves overall outcomes while eliminating these side effects. Additionally, we show that delayed/subacute IV IL-1α administration ameliorates functional deficit and promotes neurorepair.ConclusionsTaken together, our present study suggests for the first time that IL-1α could, unexpectedly, be an effective ischemic stroke therapy with a broad therapeutic window.

A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation

Cell therapies that invoke pleiotropic mechanisms may facilitate functional recovery in patients with stroke. Based on previous experiments using microglia preconditioned by oxygen-glucose deprivation, we hypothesized that the administration of peripheral blood mononuclear cells (PBMCs) preconditioned by oxygen-glucose deprivation (OGD-PBMCs) to be a therapeutic strategy for ischemic stroke. Here, OGD-PBMCs were identified to secrete remodelling factors, including the vascular endothelial growth factor and transforming growth factor-β in vitro, while intra-arterial administration of OGD-PBMCs at 7 days after focal cerebral ischemia prompted expression of such factors in the brain parenchyma at 28 days following focal cerebral ischemia in vivo. Furthermore, administration of OGD-PBMCs induced an increasing number of stage-specific embryonic antigen-3-positive cells both in vitro and in vivo. Finally, it was found to prompt angiogenesis and axonal outgrowth, and functional recovery after cerebral ischemia. In conclusion, the administration of OGD-PBMCs might be a novel therapeutic strategy against ischemic stroke.

Vandetanib-eluting Radiopaque Beads: Pharmacokinetics, Safety, and Efficacy in a Rabbit Model of Liver Cancer.

Background Transarterial chemoembolization with cytotoxic drugs is standard treatment for unresectable intermediate-stage hepatocellular carcinoma but achieves suboptimal outcomes because of hypoxic stress and the production of detrimental proangiogenic factors. An alternative approach using radiopaque embolization beads loaded with the antiangiogenic drug vandetanib may provide improved anticancer efficacy. Purpose To evaluate the pharmacokinetics, safety, and efficacy of vandetanib-eluting radiopaque bead (VERB) chemoembolization of rabbit liver tumors. Materials and Methods Between April 2015 and March 2016, 60 New Zealand white rabbits with VX2 liver tumors were randomly treated with VERBs at different doses, with nonloaded radiopaque beads (ROBs), or with intra-arterial vandetanib suspension (VS) or were not treated. Vandetanib plasma concentration and tumor growth at US were evaluated. Animals were euthanized after 3 days or 3 weeks. Assessment included bead distribution at x-ray imaging and histologic examination, tumor viability at histologic examination, and vandetanib tissue concentration. Group comparison analysis (Mann-Whitney, Kruskal-Wallis, and χ2 tests) and predictive factor analysis for tumor growth and viability were performed. Results Vandetanib plasma concentration was lower with VERBs than with VS (P < .01), while concentration in tumor was higher for VERBs (than for VS) at 3 days (median, 29.2 vs 2.74 ng/mg; P = .48). Tumor growth was lower with VERBs than with ROBs and with VS at both time points, with median values of +114%, +192%, and +466% at 3 weeks, respectively. Tumor viability was lower at 3 days for VERBs than for ROBs and for VS (3%, 18%, and 38%, respectively) but was not significantly different at 3 weeks. The volume of bead in tumor was a significant predictive factor for lower tumor growth in multivariable analysis at 3 days (P = .03). Drug tumor concentration was a significant predictive factor for lower tumor growth at 3 weeks (P = .04). Conclusion Vandetanib-eluting radiopaque bead chemoembolization showed a pharmacokinetic advantage over intra-arterial drug administration in a preclinical model of liver cancer. High deposition of beads and high vandetanib concentration in tumor led to stronger antitumor effects. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kim and Van den Abbeele in this issue.