Intra-arterial Injection Research Articles

Intraarterial Peptide Receptor Radionuclide Therapy Using 90Y-DOTATOC for Hepatic Metastases of Neuroendocrine Tumors

Given the high frequency of liver metastases in neuroendocrine tumor patients, we aimed to determine whether hepatic intraarterial administration of 90Y-DOTATOC peptide receptor radionuclide therapy (PRRT) would increase treatment efficacy while reducing systemic toxicity compared with systemic toxicity from intravenous administration as previously reported in the literature. Methods: PRRT-naïve adult neuroendocrine tumor patients with liver-dominant metastases were enrolled in a prospective single-center, open-label pilot study. The patients underwent baseline PET/CT using intravenous 68Ga-DOTATOC. Then, 3.5 ± 0.2 GBq (94.7 ± 5.4 mCi) of 90Y-DOTATOC were administered into the proper hepatic artery over 30 min. The first 5 patients also received intraarterial 68Ga-DOTATOC and underwent PET/CT. All patients were followed for response (RECIST, version 1.1) (primary aim 2, safety) and toxicity (Common Terminology Criteria for Adverse Events, version 4.0) (primary aim 1, efficacy) for at least 6 mo, with optional follow-up for up to 1 y. In the subset of 5 patients who underwent both intravenous and intraarterial 68Ga-DOTATOC PET/CT, tumor SUVmax was compared between intravenous and intraarterial administration for hepatic tumors, intrahepatic tumors, and uninvolved background organs (secondary aim, intravenous vs. intraarterial uptake). Results: The study was terminated after a planned analysis of the first 10 patients because of lack of efficacy. The best response was stable disease in 90% (9/10 patients) and progressive disease in 10% (1/10 patients) at 3 mo, and stable disease in 8 of 10 patients and progressive disease in 2 of 10 patients at 6 mo. One additional patient developed progressive disease after the 6-mo follow-up period but within the optional 1-y follow-up period. No partial response or complete response was observed. The 2 patients with the highest liver tumor burden died within 6 mo of treatment, with treatment considered a possible contributor. Patients who received intraarterial administration failed to demonstrate higher uptake by hepatic metastases than patients who received intravenous administration, with a median intraarterial-to-intravenous SUVmax ratio of 0.81 (range, 0.36-2.09) on a lesion level. Conclusion: Our study found that administration of PRRT via the proper hepatic artery did not reproduce the increase in hepatic tumor uptake that was previously reported. In addition, the single treatment using 90Y-DOTATOC did not induce tumor shrinkage, indicating that more treatment cycles may be required. Possible safety concerns in patients with a high liver tumor burden should inform patient selection for future studies.

Antioxidant nanomedicine with cytoplasmic distribution in neuronal cells shows superior neurovascular protection properties

This study investigated whether nitroxide radical (4-amino-TEMPOL)–containing nanoparticles (RNPs; antioxidant nanomedicine) can prevent neurovascular unit impairment caused by reactive oxygen species (ROS) after cerebral ischemia-reperfusion.C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO). The mice were randomly divided and administered intra-arterial RNPs injection (9 mg/kg, 7 μM/kg), edaravone (3 mg/kg, 17 μM/kg), or phosphate-buffered saline (control group). Survival rate and neurological score were evaluated 24 h post-injection. RNPs distribution was determined using immunofluorescence staining and blood–brain barrier (BBB) disruption using Evans blue extravasation assay. Effect of RNPs and edaravone on microglia polarization into microglia M1 and M2 was evaluated. We also determined multiple ROS-scavenging activities in brain homogenates of RNPs- and edaravone-treated animals using an electron spin resonance-based spin-trapping method.Compared with edaravone, RNPs significantly improved the survival rate and neurological deficit, inhibited BBB disruption and supported polarization of microglia into M2 microglia. RNPs were localized in endothelial cells, the perivascular space, neuronal cell cytoplasm, astrocytes, and microglia. Scavenging capacities of hydroxyl, alkoxyl, and peroxyl radicals were significantly higher in the RNPs-treated group.RNPs show promising results as a future neuroprotective nanomedicine approach for cerebral ischemia-reperfusion injury.

Visualization techniques of the facial arteries.

BackgroundAs the face is known for its extreme variation in vascular anatomy and the number of filler‐associated complications due to intra‐arterial injection is increasing, we are in need of a method to visualize anyone’s individual arterial anatomy of the face in a completely harmless way.AimsThe different medical imaging methods and a recently developed MRA protocol are reviewed.MethodsThe literature of the last twenty years—with special attention for the last five years—concerning the different medical imaging modalities of the facial arteries was reviewed.ResultsA harmless visualisation of the facial arteries is currently only possible with US or MRA. US may identify single vessels but never the complete arterial network. A combination of IR “heat enhancement” and a MRA 3D‐TOF sequence might make it feasible to visualize a large number of facial arteries in a risk‐free, radiation‐free, contrast‐free and non‐invasive way.ConclusionCurrently, a new combination of IR “heat enhancement” and a MRA 3D‐TOF sequence might be the only method to visualize a large number of facial arteries.

Unexpected radiation pneumonitis after SIRT with significant decrease in DLCO with internal radiation exposure: a case report

BackgroundIn the last years, Selective Internal Radiation Therapy (SIRT), using biocompatible Yttrium-90 (90Y) labeled microspheres have emerged for the treatment of malignant hepatic tumors. Unfortunately, a significant part of 90Y-labeled microspheres may shunt to the lungs after intraarterial injection. It can be predictable by infusing technetium-99 m-labeled macro-aggregated albumin particles through a catheter placed in the proper hepatic artery depending on the lobe to be treated with performing a quantitative lung scintigraphy. Radiation pneumonitis (RP) can occur 1 to 6 months after the therapy, which is a rare but severe complication of SIRT. Prompt timing of steroid treatment is important due to its high mortality rate. On the other hand, pulmonary diffusion capacity measured by carbon monoxide (DLCO) is an excellent way to measure the diffusing capacity because carbon monoxide is present in minimal amount in venous blood and binds to hemoglobin in the same manner as oxygen. Some authors reported that the most consistent changes after radiation therapy (RT) are recorded with this quantitative reproducible test. The relationship between the proportional reductions in DLCO and the severity of RP developing after this therapy may prove to be clinically significant.Case presentationWe herein present a patient who developed RP after SIRT that could be quantified using DLCO. To the best of our knowledge, this case is the first who developed unexpected RP after SIRT with significant decrease in DLCO with internal radiation exposure.ConclusionsRP is a very rare complication and may lead to a fatal outcome. Decline in DLCO could be a valuable parameter for follow-up and to identify potential candidates for RP and could be also another trigger for administration of steroid therapy with prompt timing in this patient group.

Single-dose toxicity study by intra-arterial injection of 10BSH entrapped water-in-oil-in-water emulsion for boron neutron capture therapy to hepatocellular carcinoma

We developed a mixing medical device by attaching Shirasu porous glass Millipore membrane to prepare water-in-oil-in-water (WOW) emulsion in a shorter time to be applied as 10B-entrapped WOW emulsion for hepatocellular carcinoma (HCC) treatment. Single-dose toxicity studies by intra-arterial injection of 10BSH-entrapped WOW were performed in rabbits and pig, and no side effects were observed. We hope to proceed to the preclinical and clinical studies for further evaluation of 10B compound as multidisciplinary treatments for HCC.

Pedicled flap from the first dorsal branch of the proper palmar digital artery of the fingers: An anatomy study

The pedicled flap from the first dorsal branch of the proper palmar digital artery (FBPPDA) of the fingers is an option for reconstructing digital skin defects. It has the advantage of being innervated by the dorsal branch of the proper palmar digital nerve (DBPPDN) associated with the artery. However, no studies on the anatomical variations of the neurovascular pedicle have been performed yet. The objective of our study was to evaluate the anatomical variations in the neurovascular pedicle, determine its relationships with other anatomical structures, describe the dissection technique for the FBPPDA and explore potential indications. We conducted an anatomical study with eight upper limbs from fresh adult cadavers. Twenty-six fingers (6 index, 6 middle, 8 ring, 8 little) were dissected after intra-arterial silicone injection. We found a pedicle composed of the FBPPDA and the DBPPDN in all fingers. The artery arises an average 19mm from the bifurcation of the common palmar digital artery. The DBPPDN's configuration relative to the FBPPDA varied; in the main variant – found in 58% of cases – the nerve was superficial and proximal position to the artery. After its origin, the pedicle ran on the superficial aspect of the extensor hood along an oblique path from proximal to distal and from palmar to dorsal. Its path ended with its penetration into the skin paddle of the flap just upstream the proximal interphalangeal (PIP) joint. The skin paddle corresponded to the functional skin unit represented by the dorsal surface of the middle phalanx and that of the PIP joint. Its average length was 33mm (26–40) and its average width was 21mm (15–30). The arc of rotation was sufficient to reach homodigital and heterodigital cutaneous defects. Based on our findings, this flap is a reliable and reproducible option for finger skin defects. The size of its paddle and its innervation make it an interesting alternative to conventional flaps.

Infrared Thermally Enhanced 3-Dimensional Time of Flight Magnetic Resonance Angiography Imaging for the Visualization of the Arteries of the Face.

BackgroundThe face is known for its extreme variation in vascular anatomy. Furthermore, the rapidly increasing number of filler treatments leads to an increase in severe filler-associated complications (such as skin necrosis and blindness) due to intra-arterial injection. Visualizing a patient’s individual complete facial arterial anatomy in a contrast- and radiation-free way has not been published before. This innovative imaging technique could, therefore, enhance the safety of minimally invasive surgical procedures as it provides a harmless way to map the arteries of the face.ObjectivesEvaluate a newly developed imaging technique to visualize the arteries of the face in a noninvasive and radiation-free manner.MethodsThe individual arterial facial anatomy of 20 volunteers was studied by an imaging technique, combining infrared (IR) facial warming and 3-dimensional (3D) time of flight (TOF) magnetic resonance angiography (MRA). The source and maximum intensity projection images were assessed by 2 investigators, familiar with the anatomy of the face.ResultsThe MRA technique visualized most of the main facial arteries, albeit in a variable way. The main facial branches of the external carotid artery (facial, angular, supralabial, and superficial temporal arteries) were illustrated well, whereas the visualization of the internal carotid branches (supratrochlear and supraorbital arteries) and nasal branches (dorsal nasal and lateral nasal arteries) was less consistent.ConclusionsThe combination of IR “heat-induced enhancement” and a 3D-TOF MRA sequence may actually be an important step toward the visualization of the variable facial vascular anatomy in a noninvasive, radiation-free, and contrast-free manner.

Expression of HIF-1α is a predictive marker of the efficacy of neoadjuvant chemotherapy for locally advanced cervical cancer.

Platinum-based, arterial infusion chemotherapy as a neoadjuvant chemotherapy (NACT) followed by hysterectomy may be efficient for the treatment of locally advanced cervical cancer and improve prognosis. It is important to predict whether the NACT would be effective before it is launched. Hypoxia inducible factor-1α (HIF-1α) is the master transcriptional regulator of the cellular response to altered oxygen concentration. HIF-1α protein expression is elevated in numerous human malignancies, contributes to poor disease outcome, and has been reported to induce tumorigenesis and chemoresistance. In the present study, patients with International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer (n=59) between 2008 and 2014 were assessed for HIF-1α expression by immunohistochemistry. Tumor samples were obtained by biopsy before any treatment. A double-path chemotherapy regimen, paclitaxel (intravenous) plus cisplatin (intra-arterial injection into the uterine region), was used as NACT. The patients were then separated into two groups according to NACT response: One group comprised patients with NACT, for whom the response to treatment was efficient resulting in complete/partial remission of the tumor (CR + PR group; n=52), the other group contained patients with NACT, for whom the result of the treatment was a stable/progressive disease (SD + PD group; n=7). HIF-1α expression was tested in paraffin-embedded sections using immunohistochemistry. HIF-1α expression was significantly higher in the SD + PD group compared with the CR + PR group (P=0.029). The overall survival time was significantly longer in the CR + PR group compared with the SD + PD group (P<0.001). When the patients were divided into two groups based on HIF-1α expression levels. Low (weighted score ≤4, n=39) and high (weighted score ≥6, n=20) expression level groups; the low HIF-1α expression group was significantly more susceptible to NACT treatment (P=0.025). Cox hazard analysis revealed that a high level of HIF-1α expression and lymph node metastases were significant independent predictors of poor overall survival (P=0.025, HR=6.354; P=0.020, HR=6.909, respectively). These results indicated that the expression of HIF-1α may be able to predict the efficiency of NACT and may be considered an independent prognostic factor for stage IIB-IIIB cervical cancer.

Stability study of autologous mesoangioblasts intermediate and drug product for myogenic stem cell therapy for m.3243A>G mutation carriers

Background & Aim Stem cell therapy for m.3243A>G mutation carriers consists of autologous myogenic stem cells, called mesoangioblasts (MABs), obtained from a skeletal muscle biopsy, which are expanded ex vivo for autologous intra-arterial injection to induce muscle regeneration. During the manufacturing of MABs for clinical use, the intermediate product is stored in the gas phase of liquid nitrogen. Before administration, the intermediate product is thawed, cultured for 1 passage and formulated in a syringe. During formulation, cells are labelled with IC Green to enable detection of autologous MABs in the muscle after intra-arterial administration. The drug product will be formulated in Hypothermosol FRS with 5IU/ml heparin, packaged in a syringe and stored at 2-8°C during shipping to the clinical site. Stability studies were set up to assess stability of MABs intermediate and drug product. Methods, Results & Conclusion Viability, sterility, identity (CD13+ and CD44+ cells) and impurities (CD31+, CD34+, CD45+ and CD56+ cells) (assessed by flowcytometry) were measured for both intermediate and drug product. Furthermore, recovery after thaw and endotoxin was determined for the MABs intermediate product and IC Green fluorescent signaling was visualized for the MABs drug product. MABs intermediate product stability was assessed at time points 0, 1, 3, 6 and 12 months. MABs drug product stability was assessed at time points 0, 24 and 30 hours. See table 1 for acceptance criteria. MABs intermediate product stored in the gas phase of liquid nitrogen is stable for at least 6 months, as viability, sterility, identity, impurities, recovery after thaw and endotoxin are conform acceptance criteria. MABs final formulated drug product stored in a syringe at 2-8°C is stable for at least 30 hours, since viability, sterility, identity and impurities have met the acceptance criteria. These stability data support the shipment of MABs fresh drug product at 2-8°C from the GMP manufacturing facility to the clinical site.

Targeted Repair of Vascular Injury by Adipose-Derived Stem Cells Modified with P-Selectin Binding Peptide.

Percutaneous coronary intervention for coronary artery disease treatment often results in pathological vascular injury, characterized by P‐selectin overexpression. Adipose‐derived stem cells (ADSCs) therapeutic efficacy remains elusive due to poor ADSCs targeting and retention in injured vessels. Here, conjugated P‐selectin binding peptide (PBP) to polyethylene glycol‐conjugated phospholipid derivative (DMPE‐PEG) linkers (DMPE‐PEG‐PBP; DPP) are used to facilitate the modification of PBP onto ADSCs cell surfaces via hydrophobic interactions between DMPE‐PEG and the phospholipid bilayer. DPP modification neither has influence on ADSCs proliferation nor apoptosis/paracrine factor gene expression. A total of 5 × 10−6 m DPP‐modified ADSCs (DPP‐ADSCs) strongly binds to P‐selectin‐displaying activated platelets and endothelial cells (ECs) in vitro and to wire‐injured rat femoral arteries when administered by intra‐arterial injection. Targeted binding of ADSCs shields injury sites from platelet and leukocyte adhesion, thereby decreasing inflammation at injury sites. Furthermore, targeted binding of ADSCs recovers injured ECs functionality and reduces platelet‐initiated vascular smooth muscle cells (VSMCs) chemotactic migration. Targeted binding of DPP‐human ADSCs to balloon‐injured human femoral arteries is also demonstrated in ex vivo experiments. Overall, DPP‐ADSCs promote vascular repair, inhibit neointimal hyperplasia, increase endothelium functionality, and maintain normal VSMCs alignment, supporting preclinical noninvasive utilization of DPP‐ADSCs for vascular injury.

Method of Intra‐Arterial Administration in a transient MCAO Rat model to mimic the treatment of the human patient

Endovascular thrombectomy is routinely performed in patients undergoing a large vessel occlusion. This process not only allows for the removal of a blood clot but also for the selective delivery of potential therapeutics directly to the site of injury. The intra‐arterial (IA) route of drug administration in the mouse was developed to bridge the gap between animal stroke treatments and clinical stroke therapy. We have previously shown this delivery method targets the site of injury while blunting systemic effects that have proven problematic with intraperitoneal routes. Here, we adapted the IA method for use in rats, combining it with a clinically relevant large vessel occlusion stroke model (MCAO). Our goal was to characterize variances in the model in order to optimize potential therapeutic delivery methods to the ipsilaterally affected hemisphere. Male and female Sprague‐Dawley rats (4 months of age) were subjected to placement of micro‐angio tubing at the bifurcation of the common carotid artery (CCA), with delivery through the internal carotid artery (ICA). We then determined the optimal infusion rate and volume using injection of India ink and evaluation of vascular distribution within the brain and the liver. Importantly, we found the infusion rate and volume varied depending on sex and body weight. India ink was selectively delivered to the ipsilateral side of the brain in males (370–460 g) at 4 μl/min with a max volume of 25 μl and in females (250–300 g) at 2.5 μl/min with a max volume of 25 μl. Following these guidelines, no ink was observed in the liver of these animals, indicating reduced systemic circulation of administered compounds. We then performed a 5‐hour transient MCAO, on male and female Sprague‐Dawley rats (4 months of age), to mimic human stroke, since 5 hours is the average time from the clinical presentation of stroke to the thrombectomy procedure. A silicone coated monofilament was advanced till resistance was felt, occluding the MCA territory. At the 5 hour time point, we removed the monofilament and inserted the mico‐angio tubing at the same entry point on the bifurcation of the CCA. We performed variant injections using different volumes and rates, measuring delivery of dye (India Ink) and rate of induced subarachnoid hemorrhage. A rate of 4 ul/min with a max volume of 25 ul was optimal in males, and a rate of 2.5 ul/min with a max volume of 25 ul was optimal in females. The results showed that, even with a large vessel occlusion, and removal of the monofilament (recanalization), the IA injection using these sex‐specific rates and volumes resulted in appropriate limited dye delivery without ruptured subarachnoid hemorrhage. This IA method is ideally suited for combination with the MCAO stroke model and mirrors the human patient undergoing an endovascular thrombectomy. This model provides an investigative opportunity to test neuroprotective drugs and other pharmacotherapies.Support or Funding InformationUniversity of Kentucky Center for Advanced Translational Stroke Science, Surgery Core

Descripción de la experiencia en pacientes diagnosticados con insulinoma. Estudio multicéntrico en Medellín, Colombia

Objetivo: describir la experiencia de los pacientes con insulinoma, diagnosticados y tratados entre los años 2002 y 2017 en tres hospitales de la ciudad de Medellín, Colombia.&#x0D; Métodos: estudio descriptivo y retrospectivo de pacientes con criterios bioquímicos para hipoglucemia hiperinsulínica y confirmación histopatológica de insulinoma.&#x0D; Resultados: se estudiaron 19 casos, 10 eran mujeres (52,6 %), la edad media al diagnóstico fue 43 años (D.E 15,5). Hubo cuatro casos de insulinoma multifocal (21,1 %), tres asociados con NEM-1 (15,8 %) y dos malignos (10,6 %). Todos presentaron hipoglucemia en ayunas y 63,2 % posprandial. En la prueba de ayuno, el nadir de glucemia sucedió antes de 48 horas en todos los casos, en promedio 9 horas (D.E 8,0). El diagnóstico bioquímico fue realizado con hipoglucemia e insulina elevada en todos los casos, aunque el péptido C fue reportado en nueve pacientes (47,3 %) y las sulfonilureas en dos (11,1 %). La localización preoperatoria se hizo por imágenes en 12 individuos (68,5 %) y las pruebas invasivas fueron necesarias en seis (31,5 %). Las pruebas diagnósticas fueron positivas en un 83 % para resonancia, 50 % para ecografía endoscópica y prueba de estímulo intraarterial con calcio y 100 % para ecografía intraoperatoria. La cirugía se realizó en 18 casos (94,7 %). La mortalidad (15,8 %) fue derivada de complicaciones en el posoperatorio temprano; la curación se logró en todos los casos.&#x0D; Conclusiones: el insulinoma en nuestro medio tiene características demográficas y clínicas similares a otras series. Existen limitaciones locales para el acceso a los estudios bioquímicos y en el rendimiento diagnóstico de las pruebas de localización.

Acute Upper Limb Ischemia after an Accidental Intra-Arterial Antispasmodic Injection on an Anatomical Variant of the Radial Artery: A Case Report and Review of the Literature

Acute Upper Limb Ischemia after an Accidental Intra-Arterial Antispasmodic Injection on an Anatomical Variant of the Radial Artery: A Case Report and Review of the Literature

Upper Limb Arterial Ischemia Occurred After Accidental Antibiotics Intra-Arterial Injection: Report of Three Cases

Upper Limb Arterial Ischemia Occurred After Accidental Antibiotics Intra-Arterial Injection: Report of Three Cases

The effectiveness of various cytotherapeutic strategies for the treatment of ischemic stroke: a Bayesian network meta-analysis of randomized controlled trials.

Cytotherapy is a potential treatment for ischemic stroke (IS) patients but lacks uniform procedures. We aimed to assess the impact of the time of intervention, cell type, dose, and route of administration on the clinical effects by network meta-analysis. We searched public electronic databases through July 7, 2019. Bayesian network meta-analyses were performed to compare differences among different cytotherapeutic strategies. Cytotherapy can significantly improve patients' activity of daily living according to the modified Rankin Scale (standard mean difference (SMD) - 0.81; 95% confidence interval (CI) - 1.58, - 0.03; p = 0.0417) and Barthel Index (SMD 0.67; 95% CI 0.05, 1.30; p = 0.036) results as well as improve neurological recovery (SMD - 0.93; 95% CI - 1.29, - 0.57; p < 0.001). Network meta-analysis showed that the intra-arterial injection of large amounts of mononuclear cells (NCs) or aldehyde dehydrogenase (ALDH)-positive cells was beneficial for improving patients' activity of daily living, while CD34+ cells through intracerebral injection had an advantage in the recovery of injured nerve function. Intravenous injection of mesenchymal stem cells (MSCs) or endothelial progenitor cells (EPCs) was beneficial in reducing mortality and serious adverse event (SAE) onset. In the subacute stage, the intra-arterial injection of NCs or ALDH cells improves patients' activity of daily living. Additionally, CD34+ cells through intracerebral injection had an advantage in the recovery of injured nerve function even in the chronic stage. Intravenous injection of MSCs or EPCs is a safety delivery route that can reduce mortality and SAE onset. However, further clinical studies are still needed to confirm these results.

Efficacy of Dexmedetomidine as an Adjuvant to Bupivacaine in Peripheral Nerve Block - Three Prospective Randomized Controlled Studies

Abstract Introduction Peripheral nerve blocks are frequently used as the sole anesthetic technique or as an adjuvant to general anesthesia, However, the duration of sensory nerve block after single doses of long-acting local anesthetics is not consistent enough to avoid the use of postoperative opioids. Many adjuvants have been added to prolong the duration of nerve block, It was recently suggested that, based on current evidence, perineural dexmedetomidine is the most promising adjuvant to extend the duration of long-acting local anesthetics Aim The aim of this work is to study the effects of dexmedetomidine as an adjuvant to bupivacaine in various peripheral nerve blocks. The study will include: supraclavicular brachial plexus block, paravertebral block and femoral nerve block. Patients Adult patients of either sex aged 25 – 60 years, ASA physical status I and II, Elective surgeries appropriate for the nerve block. Methods patients received bupivacaine 0.5% alone in (group I) or bupivacaine 0.5% combined with 100 dexmedetomidine (group II) in peripheral nerve blocks. Motor and sensory block onset times; durations of blockades and analgesia were recorded Results Sensory and motor block onset times were shorter in group II than in group I. Sensory and motor blockade durations were longer in group II than in group I. Duration of analgesia was longer in group II than in group I. Systolic, diastolic arterial blood pressure levels, and heart rate were less in group II. Conclusion In the current study, it was obvious that:(Addition of dexmedetomidine to bupivacaine in supraclavicular nerve block, paravertebral nerve block and femoral nerve block has shortened the onset times of both sensory and motor blocks and significantly prolonged their durations, Dexmedetomidine had also the added effect of sedation with minimal side effects, which makes it a beneficial adjuvant to local anesthetics in peripheral nerve blocks, Addition of dexmedetomidine to bupivacaine prolonged the postoperative analgesia with subsequent consumption of less amount of analgesics and The use of ultrasonography in performing nerve blocks significantly reduced the incidence of complications such as pneumothorax or intra-arterial injection and hence, lowered the incidence of systemic toxicity of local anesthetics).

Peritumoral administration of IFNβ upregulated mesenchymal stem cells inhibits tumor growth in an orthotopic, immunocompetent rat glioma model

BackgroundImmunotherapy with IFNβ is a promising strategy for treating malignant glioma. However, systemic administration of IFNβ is inadequate because of low intratumoral concentration and major adverse effects. This study aimed...

Instillation of bradykinin into femoral artery elicits cardiorespiratory reflexes involving perivascular afferents in anesthetized rats.

The physiology of baroreceptors and chemoreceptors present in large blood vessels of the heart is well known in the regulation of cardiorespiratory functions. Since large blood vessels and peripheral blood vessels are of the same mesodermal origin, therefore, involvement of the latter in the regulation of cardiorespiratory system is expected. The role of perivascular nerves in mediating cardiorespiratory alterations produced after intra-arterial injection of a nociceptive agent (bradykinin) was examined in urethane-anesthetized male rats. Respiratory frequency, blood pressure, and heart rate were recorded for 30 min after the retrograde injection of bradykinin/saline into the femoral artery. In addition, paw edema was determined and water content was expressed as percentage of wet weight. Injection of bradykinin produced immediate tachypneic, hypotensive and bradycardiac responses of shorter latency (5-8 s) favoring the neural mechanisms involved in it. Injection of equi-volume of saline did not produce any responses and served as time-matched control. Paw edema was observed in the ipsilateral hind limb. Pretreatment with diclofenac sodium significantly attenuated the bradykinin-induced responses and also blocked the paw edema. Ipsilateral femoral and sciatic nerve sectioning attenuated bradykinin-induced responses significantly, indicating the origin of responses from the local vascular bed. Administration of bradykinin in the segment of an artery produced reflex cardiorespiratory changes by stimulating the perivascular nociceptors involving prostaglandins. This is a novel study exhibiting the role of peripheral blood vessels in the regulation of the cardiorespiratory system.

Abstract No. 438 Tail artery access for transarterial experiments in rats: feasibility study in a survival model

The rat is an increasingly valuable model to study interventional therapeutic procedures. Suitable arterial access is essential for vascular intervention. In rats, transtail artery access has been recently reported as a feasible technique compared to conventional carotid or femoral access. The aim of this study was to evaluate repeat accessibility and complications of transtail angiography in a survival model. Seventeen male Sprague-Dawley rats were used (460.2 ± 45.0g), one rat died before the procedure, hence 16 rats were included in this study. 1-cm longitudinal ventral incisions were created 5 cm distal to the base of the tail to dissect the tail artery (ventral caudal artery). A 1.5–1.7 Fr microcatheter was advanced over a 0.010–0.014 inch microguidewire through a partial arteriotomy. Selective renal angiography was then performed. Intraarterial antibiotics injection was performed in 11 of 16 rats. The accessed segment of the tail artery was ligated and the incision closed with sutures. Repeat renal angiography via the tail artery was performed 48 hours after the initial procedure using a separate tail incision 1 cm proximal to the initial incision. Procedure time from skin incision to catheterization was recorded. Complications including tail ischemia, infection and bleeding were evaluated during the 2-day follow-up period. All initial and repeat procedures were successfully performed. The average time for the 32 tail artery cannulations was 11.0 ± 4.5 min. Transient focal skin color change in the tail was observed in one rat immediately after the initial procedure, which resolved within 90 mins. No tail necrosis, major bleeding or signs of infection were observed. Dehiscence of the incision was observed in 3 of 16 rats from self-grooming, with no bleeding or infection. Repeat tail artery access for angiography in rats was successful without major complications in a survival model. This reproducible technique can provide a new experimental platform to test transarterial procedures.

Intra-arterial Injection of Lidocaine as a Cell Sensitizer during Irreversible Electroporation

PurposeTo investigate whether intra-arterial injection of lidocaine enhances irreversible electroporation (IRE) in a liver model. Materials and MethodsConventional IRE (C-IRE) and lidocaine-enhanced IRE (L-IRE) were performed in 8 pig livers. Protocol 1 (tip exposure and electrode distance of 2.0 cm each) and protocol 2 (increased tip exposure and electrode distance 2.5 cm each) were used. Animals were sacrificed 3 hours after IRE. Study goals included electrical tissue properties (eg, current, conductivity) during IRE, geometry of IRE zones analyzed using computed tomography and magnetic resonance imaging (eg, volume and sphericity index), degree of acute liver damage, and irreversible cell death analyzed using microscopy (hematoxylin and eosin staining and terminal deoxynucleotidyl transferase deoxyuridine 5-triphosphate nick end labeling). Statistical comparisons were performed using the paired t test and Wilcoxon test. ResultsAll treatments were performed without adverse events. Electrical tissue properties were not significantly different between C-IRE and L-IRE. For protocol 1, the diameter of the largest sphere within the IRE zone was significantly larger for L-IRE than for C-IRE (25.0 ± 4.7 mm vs 18.4 ± 3.1 mm [P = .013]). For protocol 2, the volume of IRE zone was significantly larger for L-IRE compared with C-IRE (46.0 ± 5.4 cm3 vs 22.6 ± 6.4 cm3 [P = .018]), as well as the diameter of the largest sphere within the IRE zone (27.1 ± 2.2 mm vs 19.8 ± 2.3 mm [P = .020]). For protocol 1, a significantly higher degree of irreversible cell death was noted for L-IRE than for C-IRE (1.8 ± 1.0 vs 0.8 ± 1.0 [P = .046]). ConclusionsIntra-arterial injection of lidocaine can enhance IRE in terms of larger IRE zones and an increase of irreversible cell death.