Arterial Injection Research Articles

Efficacy of Percutaneous Intraarterial Facial/Supratrochlear Arterial Hyaluronidase Injection for Treatment of Vascular Embolism Resulting From Hyaluronic Acid Filler Cosmetic Injection.

Vascular embolism is a serious complication of hyaluronic acid (HA) filler cosmetic injection, and hyaluronidase injection has been proposed as the treatment. Until now, there has been a lack of adequate clinical evidence regarding the benefits of treatment for HA filler-induced vascular embolism by percutaneous facial or supratrochlear arterial hyaluronidase injection. The authors sough to evaluate the efficacy of percutaneous facial or supratrochlear arterial hyaluronidase injection as a rescue treatment for HA filler-induced vascular embolism. We included 17 patients with vascular embolism after facial HA filler injection. Intraarterial injection of 1500 units hyaluronidase was performed via facial artery for 13 cases with skin necrosis and via supratrochlear arterial for 4 cases with severe ptosis and skin necrosis but no visual impairment. Simultaneously, general symptomatic treatment and nutritional therapy were performed. After hyaluronidase injection, facial skin necrosis in all cases was restored and ptosis in the 4 cases was also significantly relieved. Patients were subsequently followed-up for 1 month to 1 year. The skin necrosis in 16 patients completely healed, and only 1 patient had small superficial scars. It is effective to alleviate skin necrosis and ptosis resulting from HA filler embolism via percutaneous facial or supratrochlear arterial hyaluronidase injection.

Spatiotemporal Measurement of Arterial Pulse Waves Enabled by Wearable Active-Matrix Pressure Sensor Arrays.

Wearable pressure sensors have demonstrated great potential in detecting pulse pressure waves on the skin for the noninvasive and continuous diagnosis of cardiac conditions. However, difficulties lie in positioning conventional single-point sensors on an invisible arterial line, thereby preventing the detection of adequate signal amplitude for accurate pulse wave analysis. Herein, we introduce the spatiotemporal measurements of arterial pulse waves using wearable active-matrix pressure sensors to obtain optimal pulse waveforms. We fabricate thin-film transistor (TFT) arrays with high yield and uniformity using inkjet printing where array sizes can be customizable and integrate them with highly sensitive piezoresistive sheets. We maximize the pressure sensitivity (16.8 kPa-1) and achieve low power consumption (101 nW) simultaneously by strategically modulating the TFT operation voltage. The sensor array creates a spatiotemporal pulse wave map on the wrist. The map presents the positional dependence of pulse amplitudes, which allows the positioning of the arterial line to accurately extract the augmentation index, a parameter for assessing arterial stiffness. The device overcomes the positional inaccuracy of conventional single-point sensors, and therefore, it can be used for medical applications such as arterial catheter injection or the diagnosis of cardiovascular disease in daily life.

Targeting the BMP Pathway in Prostate Cancer Induced Bone Disease.

From the 33,000 men in the U.S. who die from prostate cancer each year, the majority of these patients exhibit metastatic disease with bone being the most common site of metastasis. Prostate cancer bone metastases are commonly blastic, exhibiting new growth of unhealthy sclerotic bone, which can cause painful skeletal related events. Patient’s current care entails androgen deprivation therapy, anti-resorptive agents, radiation, and chemotherapy to help control the spread of the cancer but little intervention is available to treat blastic bone disease. The transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) pathways are known to regulate bone growth and resorption of destructive lytic bone lesions, yet the role of TGFβ/BMP signaling in prostate cancer blastic vs lytic bone lesions are not fully understood. We hypothesized that to target the BMP/TGFβ pathway, a useful biomarker of bone lytic or blastic pathology would have superior response. We show distinct BMP vs. TGFβ signaling in clinical samples of human prostate cancer bone metastases with either lytic or blastic pathologies. BMPs exhibit distinct effects on bone homeostasis, so to examine the effect of BMP inhibition on healthy bone, we treated mice with the BMP receptor small molecule antagonist DMH1 and saw a modest temporary improvement in bone health, with increased trabecular bone. We next sought to use the BMP inhibitor DMH1 to treat bone metastasis engraftment seeded by a caudal artery injection of the lytic human prostate cell line PC3 in immunodeficient mice. The colonization by PC3 cells to the bone were restricted with DMH1 treatment and bone health was importantly preserved. We next proceeded to test BMP inhibition in an injury model of established bone metastasis via intratibial injection of the MYC-CaP mouse prostate cell line into FVBN syngeneic mice. DMH1 treated mice had a modest decrease in trabecular bone and reduced lymphocytes in circulation without affecting tumor growth. Taken together we show unique responses to BMP inhibition in metastatic prostate cancer in the bone. These studies suggest that profiling bone lesions in metastatic prostate cancer can help identify therapeutic targets that not only treat the metastatic tumor but also address the need to better treat the distinct tumor induced bone disease.

Unresectable primary hepatic adenosquamous carcinoma successfully treated with systemic and transcatheter hepatic arterial injection chemotherapies followed by conversion surgery: a case report and literature review

BackgroundPrimary hepatic adenosquamous carcinoma (ASC) is a type of tumor that has the features of both adenocarcinoma and squamous cell carcinoma (SCC). The prognosis for patients with ASC is poor, as the chemotherapy has been ineffective so far.Case presentationHere, we report a case of a 62-year-old male patient who presented with high fever. The tumor marker levels were high, and abdominal dynamic computed tomography showed a liver tumor and distant lymph node metastases. Upon further investigation, needle biopsy of the liver tumor showed a primary hepatic SCC. Because the SCC was unresectable, the patient was treated with tegafur/gimeracil/oteracil (S-1) and transcatheter hepatic arterial injection (TAI) of cisplatin. After chemotherapy, a surgical resection performed on the remaining liver tumor, made the patient cancer-free. After the operation, the liver tumor was confirmed as primary hepatic ASC. Subsequently, the patient was administered postoperative adjuvant chemotherapy, which prevented its recurrence.ConclusionsDue to the lack of an effective treatment for primary hepatic ASC, its prognosis is poor. Here, we suggest that a chemotherapy combination of 5-fluorouracil (S-1) and cisplatin along with conversion surgery might be an effective way for treating primary hepatic ASC. Our experience from this case shall be valuable to clinicians around the world involved in the treatment of primary hepatic ASC.

73 Off-label use and safety of drug use in vascular anomalies

Abstract Primary Subject area Clinical Pharmacology and Toxicology Background Vascular anomalies (VA) represent a heterogeneous group of disorders associated with an abnormal development and proliferation of blood and/or lymphatic vessels displaying variable clinical presentations and severity. Infantile hemangiomas, venous, and lymphatic malformations, for example, are commonly encountered in children. Other, less frequent diagnostics include Klippel-Trenaunay syndrome and PIK-3CA-related overgrowth spectrum (PROS). Severe phenotypes can alter organ function and/or lead to pain and chronic functional impairment, and are associated with significant morbidity and mortality. Management includes surgical, interventional radiology, and pharmacologic modalities. Drugs are administered by systemic (e.g., oral, intravenous) or local (topical, intralesional) routes, or by sclerotherapy (endovascular or percutaneous venous, lymphatic, or arterial injection). Off-label drug use is common in pediatrics and in rare diseases, two characteristics applying to vascular anomalies (VA). Off-label use is associated with an increased risk of adverse drug reactions. Objectives To quantify off-label drug use in VA and assess its safety. Design/Methods A guidelines search was conducted to extract a list of drugs used in VA management. The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data. A drug was considered to have significant safety concerns if a black box warning (the FDA’s most stringent warning dedicated to serious or life-threatening risks) or if a serious adverse drug reaction was reported in at least 1% of the patients (leading to hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). Results Among 87 drugs, 13 were unlicensed and 73 off-label. Figure 1 describes the reason for considering the 73 drugs off-label. Among 74 licensed drugs, only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas (IH) is approved. 98.9% of the drugs are used off-label or unlicensed. Except infantile hemangioma, all other VA are exclusively treated with off-label drugs. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs (Figure 2). Conclusion This first study determining the rate of off-label drug use in vascular anomalies shows that off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is needed to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients and families should be openly informed and involved in the decision-making process.

Fragmentation of microspheres after bronchial artery injection: a case report and review of the\xa0literature

BackgroundMassive hemoptysis due to aspergilloma is a rare but life-threatening complication. Bronchial artery embolization is recommended as a definitive treatment for massive hemoptysis. Polyvinyl alcohol is widely used in bronchial artery embolization. A very small number of studies have reported disrupted polyvinyl alcohol, which may cause ectopic embolism.Case presentationThis case highlights an unusual phenomenon in which polyvinyl alcohol fragments appeared on pathological examination in a 61-year-old man, ethnic Han, with massive hemoptysis caused by aspergilloma for whom bronchial artery embolization failed. Lobectomy was carried out successfully. Hematoxylin and eosin stain provides clear images of polyvinyl alcohol fragments, while alpha-smooth muscle cell actin and cluster of differentiation-34 immunohistochemistry revealed their localization in bronchioles.ConclusionThus far, only two cases of polyvinyl alcohol fragments in the lung have been reported, and the mechanism has not been elucidated. These two cases revealed no counter-indication for the use of polyvinyl alcohol. However, in some cases of off-target embolization causing fatal complications, such as stroke, paraplegia, and myocardial, polyvinyl alcohol fragmentation needs to be taken into consideration.

頭蓋底骨折後遅発性に鼻出血を契機に発見された内頸動脈仮性瘤の1例(A case of delayed discovery of a internal carotid artery pseudoaneurysm by nosebleeds after skull base fracture)

要旨 頭部外傷に伴う頭蓋底骨折はときに仮性動脈瘤を合併する。今回我々は，頭蓋底骨折後受傷時に損傷を認めなかった右内頸動脈に遅発性に仮性動脈瘤を形成した1例を経験したので報告する。症例は74歳の男性。約3mの高さから墜落し顔面を強打した。救急隊接触時，外表上頭部・顔面に外傷を認め，発語不能であったため，重症頭部外傷が疑われ当院へ搬送された。来院時CT検査において右視神経損傷を伴う頭蓋底骨折，脳挫傷，外傷性くも膜下出血，右肩甲骨骨折，多発肋骨骨折を認めたが，仮性動脈瘤は認めなかった。上記各外傷に対し保存的加療を行い，第19病日軽快転医となった。第38病日初回の鼻出血を認めた。第47病日中等量の鼻出血を認め，鼻腔内ガーゼ充填で止血を得た。第79病日より隔日で鼻出血を認めるようになったが，耳鼻科診察では鼻粘膜に特記すべき異常を認めなかった。第84病日多量の鼻出血と血圧低下，冷汗を認め，造影CTで右内頸動脈に仮性動脈瘤を認めたため，当院へ再度転医となった。第85病日右浅側頭動脈–中大脳動脈吻合術および右内頸動脈瘤コイル塞栓術を行い，第90病日MRAで瘤への血流がないことを確認した。第96病日に転医し，第106病日独歩退院となった。本症例では頭部外傷後の鼻出血により，仮性動脈瘤を発見し得た。頭蓋底骨折後の血管評価は受傷時に損傷を認めなくても継時的な画像評価などを慎重に行う必要がある。

Vasa nervorum of epicardial nerves and valves of small veins investigated in porcine heart by two types of vascular injections.

The morphology of the vascular supply of peripheral branches of cardiac nerves has not been systematically described until now. The aim of this study was to describe the architectonics of the vasa nervorum of epicardial nerves in porcine hearts by using two injection techniques. Twenty-three hearts from young healthy pigs were used. In 10 hearts India ink solution was injected into the origin of the anterior interventricular branch. In another 10 hearts India ink solution was injected retrogradely through the coronary sinus. The hearts were then analyzed using a magnifying glass and light microscopy. The arterial injection showed the entirety of the rich venous components of the vasa nervorum, which often consisted of paired veins accompanying the epicardial nerves. The thickness of the nerves ranged from 50 to 815 μm. The vasa nervorum drained into larger subepicardial veins. In seven of the hearts prepared with venous injections the vasa nervorum of epicardial nerves were visualized in the same detail as in the arterial preparations and India ink solution filled the right ventricle via the smallest cardiac veins. The histological analysis of these seven hearts showed complete dehiscence and functional insufficiency of small and larger veins valves. In the other three hearts prepared with venous injections the valves were competent, which prevented retrograde filling of larger and smaller veins. The results obtained expand the current knowledge on epicardial nerves vasa nervorum and provide anatomical evidence behind the mechanism of retrograde application of cardioplegic solutions in cardiac surgery.

Intraoperative study of the functional perforasome - an experimental model.

The aim of this study is to find the most suitable protocol based on an animal experimental model, through the use of a fluorescent dye, determining also its minimal concentration needed to stain the skin after arterial injection, in order to evidence the functional perforasome by visual examination. Methylene blue solution was used in order to determine the territory vascularized by one perforator on fresh cadavers in many studies which introduced, as a final result, the concept of perforasome. One of the most frequent complications of perforator flaps is partial flap necrosis which could be avoided by correctly assessing pre-operatively the functional perforasome surface.Two groups of seven rats were used in order to establish a proper surgical protocol to evaluate the functional perforasome in vivo by injecting the dye. Also, the minimal concentration for methylene blue was experimentally determined. The direct injection into the femoral artery of the proper concentration of dye, 1mM for methylene blue and the clamping of all the branches except the medial branch of the superficial epigastric artery is a reliable model to study the functional perforasome. Our study demonstrates that the intraoperative assessment with fluorescent dye of the functional perforasome by intra-arterial injection of methylene blue is an easy, affordable and very efficient method to reduce the number of partial necrosis of the perforator flaps.

Clinical and Variant Anatomy of the Blood Supply to the Body and Tail of the Human Pancreas

The aim of the study was to specify peculiarities of the blood supply to the body and tail of the human pancreas determining topographic variants and vascular bed of the splenic artery.Material and methods. The artery basin of the pancreas body and tail was studied in 46 native and 42 organ complexes consisting of the pancreas, duodenum, spleen, retropancreatic tissue, celiac trunk with the main branches, a section of the superior mesenteric artery up to the entrance into the root of the small intestine mesentery with the preliminary artery injection by gelatin mass. The organ complexes were fixed in 10% formalin solution.Results. The study revealed two variants of the splenic artery topography in relation to the pancreas and determined the degree of tortuosity of the artery. In 31.7% of cases the vessel passed retro-pancreatically and in 68.3% suprapancreatically. Moderate tortuosity of the splenic artery was detected most frequently (44.82%); in 34.48% of cases severe tortuosity was detected; in 17.24% of cases there was no tortuosity in the artery. The correlation between area/convolution and the number of pancreatic arteries was found to be 0.864 (p=0.05), which is considered to be a high parameter according to the Cheddock scale. In severe tortuosity of the splenic artery 3.16±0.37 pancreatic arteries on average closed to the corpus caudal segment of the pancreas, in moderate tortuosity – 5.09±1.24, in straight passage – 9±1.22.Conclusion. The regularities revealed in the spleen artery topography, blood supply of the pancreas body and tail allow determining operational risks and tactics of surgical interventions on the corpus caudal segment of the pancreas.

Heme Effects in Lowering Patient Discomfort in Radial Artery Verapamil Injection.

BackgroundThe primary objective of this study was to evaluate whether diluting verapamil with heme as compared to normal saline reduces patient discomfort during radial artery injection. Following radial artery access, verapamil is frequently administered to reduce the incidence of radial artery spasm. The injection of verapamil via the radial artery is associated with a temporary “burning” discomfort. It has been hypothesized that the dilution of verapamil with heme rather than saline leads to less patient discomfort during administration.MethodsThis prospective, single-center, randomized study enrolled patients undergoing coronary angiography via radial artery access between August 2017 and April 2018. Patients were randomized 1:1 to receive either verapamil/heme or verapamil/saline administration. Patient discomfort was assessed at the time of injection, and 1-h post procedure.ResultsA total of 214 patients were enrolled in the study. Of these, 103 patients were included in the verapamil/heme group and 100 in the verapamil/saline group. For the primary objectives, there were no statistically significant differences in patient discomfort at the time of verapamil injection (P = 0.15), or 1-h post injection (P = 0.48). However, in the verapamil/heme group, there was a trend towards a lower post-injection pain score (M = 2.83, standard deviation (SD) = 3.18) compared to the verapamil/saline group (M = 3.48, SD = 3.01) (P = 0.15).ConclusionThere was no significant difference in immediate or 1-h post-procedure patient discomfort with verapamil diluted with heme as compared to dilution with saline. While there was a trend towards lower immediate patient discomfort in the verapamil/heme group, larger studies are needed to further evaluate this trend.

Embolic Stroke Model with Magnetic Nanoparticles.

Stroke models are vital tools in neuropharmacology and rehabilitation research. However, a classic and widely used model-the suture occlusion model-is not suitable for all research approaches, especially regarding thrombolysis. For embolic stroke models in thrombolytic research, the surgical procedures of thrombin injection in the middle cerebral artery or clot injection in the carotid artery involved are too sophisticated. Here, we report a new stroke model in mice that uses magnetic nanoparticle (MNP) cross-linked with thrombin to embolize. Briefly, after the magnet was positioned in the common carotid artery, MNP@Thrombin was injected from the tail vein. Within several minutes postinjection, the MNP@Thrombin accumulated in the carotid artery and induced thrombus formation. These complex clots were flushed into and subsequently blocked the cerebral artery. Collectively, these results suggested that this new method was a quick and easy stroke model that blocked hemisphere blood flow and damaged neural function. Importantly, this model had an excellent response to thrombolytic drugs. After urokinase injection, cerebral blood flow was restored and symptom scores were enhanced by nearly one. This method, including a quick synthesis of MNP and thrombin, provided an easy and minimally invasive process for a new stroke model that is usable in both pharmacological and rehabilitative research.

Usefulness of computed tomography during arteriography in a selective arterial calcium agent injection test for pancreatic gastrinoma: a case description.

Pancreatic gastrinoma is a rare pancreatic neuroendocrine tumor with an incidence of about 0.5–21.5 cases per million people worldwide. The most common sites are the duodenum (75%), pancreas (20%), and other organs (5%). Gastrinomas are malignant in about 60–90% of cases (1-5). Malignant gastrinomas originating beneath the duodenal mucosa often metastasize to the liver, even if the tumor diameter is ≤1 cm. Therefore, in patients with gastrinoma and Zollinger–Ellison syndrome, it is important to determine the number and site(s) of gastrinoma(s), as well as the presence or absence of liver metastases. However, the detection sensitivity of computed tomography (CT) and magnetic resonance imaging is about 10–50%, that of angiography is 20–50%, and that of somatostatin receptor scintigraphy is 30–70%. Tumor size is strongly correlated with the detection sensitivity of any examination modality, and tumors of <1 cm in diameter are often difficult to detect (1,2). Therefore, the selective arterial calcium agent injection (SACI) test was developed as an effective method to detect small gastrinomas (2,6,7). In the SACI test, calcium gluconate is injected via a microcatheter into selected arterial branches to stimulate gastrin secretion from the gastrinoma located in the corresponding arterial territory. Generally, calcium gluconate is selectively injected into the gastroduodenal artery (GDA), superior mesenteric artery (SMA), distal or proximal portion of the splenic artery (distal SpA, proximal SpA), and the proper hepatic artery (PHA). The subsequent increase in the serum gastrin level is monitored using blood samples taken from the hepatic vein before and at 30, 60, 90, and 120 s after the injection. The location of the gastrinoma is determined based on a significant increase in serum gastrin levels in response to calcium gluconate (maximum serum gastrin level after calcium injection/serum gastrin level before calcium agent injection; with a median change of about 4.21 times baseline) (8). However, there are two limitations of the SACI test. First, the distribution of calcium varies between individual patients due to anatomical differences in the pancreatic arterial branches and the arterial territories. Second, there are many false positives following the injection of calcium gluconate into the GDA (median change of 4.15 times the baseline value) because calcium gluconate may stimulate normal gastrin-secreting cells in the gastric prepylorus and duodenal bulbus (8,9). It is possible to visualize the distribution of calcium following its injection by performing CT during arteriography (CTA). Here, we report a case in which the SACI test was combined with CTA for the diagnosis of a gastrinoma located in the pancreatic head and to exclude the presence of liver metastases.

Voltage-gated potassium channel dysfunction in dorsal root ganglia contributes to the exaggerated exercise pressor reflex in rats with chronic heart failure.

An exaggerated exercise pressor reflex (EPR) causes excessive sympathoexcitation and exercise intolerance during physical activity in the chronic heart failure (CHF) state. Muscle afferent sensitization contributes to the genesis of the exaggerated EPR in CHF. However, the cellular mechanisms underlying muscle afferent sensitization in CHF remain unclear. Considering that voltage-gated potassium (Kv) channels critically regulate afferent neuronal excitability, we examined the potential role of Kv channels in mediating the sensitized EPR in male rats with CHF. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting experiments demonstrate that both mRNA and protein expressions of multiple Kv channel isoforms (Kv1.4, Kv3.4, Kv4.2, and Kv4.3) were downregulated in lumbar dorsal root ganglions (DRGs) of CHF rats compared with sham rats. Immunofluorescence data demonstrate significant decreased Kv channel staining in both NF200-positive and IB4-positive lumbar DRG neurons in CHF rats compared with sham rats. Data from patch-clamp experiments demonstrate that the total Kv current, especially IA, was dramatically decreased in medium-sized IB4-negative muscle afferent neurons (a subpopulation containing mostly Aδ neurons) from CHF rats compared with sham rats, indicating a potential functional loss of Kv channels in muscle afferent Aδ neurons. In in vivo experiments, adenoviral overexpression of Kv4.3 in lumbar DRGs for 1 wk attenuated the exaggerated EPR induced by muscle static contraction and the mechanoreflex by passive stretch without affecting the blunted cardiovascular response to hindlimb arterial injection of capsaicin in CHF rats. These data suggest that Kv channel dysfunction in DRGs plays a critical role in mediating the exaggerated EPR and muscle afferent sensitization in CHF.NEW & NOTEWORTHY The primary finding of this manuscript is that voltage-gated potassium (Kv) channel dysfunction in DRGs plays a critical role in mediating the exaggerated EPR and muscle afferent sensitization in chronic heart failure (CHF). We propose that manipulation of Kv channels in DRG neurons could be considered as a potential new approach to reduce the exaggerated sympathoexcitation and to improve exercise intolerance in CHF, which can ultimately facilitate an improved quality of life and reduce mortality.

Complications of Selective Intraarterial Chemotherapy in Children with Intraocular Retinoblastoma

Introduction: Selective ophthalmic arterial injection (SOAI) therapy for intraocular retinoblastoma is currently recognized by the world ophthalmic-oncological communities and this method is used in leading specialized institutions. However, the using of this type of treatment can lead to complications. Side effects can be both systemic, affecting the course of the procedure itself, and local in nature, associated with intraocular changes.Purpose: Conduct an analysis of complications during SOAI in children with intraocular retinoblastoma.Material and methods: The study includes the results of treatment of 110 children (129 eyes) with unilateral and bilateral retinoblastoma who received SOAI both with insufficient efficacy of previous treatment for resistant and recurrent forms of RB (99 children / 116 eyes), and as primary local chemotherapy without previous treatment (11 patients / 13 eyes). 313 procedures were performed, of which the treatment stage was completed in 303 cases. Depending on the hemodynamic characteristics of the blood supply to the eye and the orbital region, 2 methods of delivering of the chemotherapy were used: 1) microcatheter technique (245 procedures performed; 81.0 %) 2) microballoon technique (58 procedures performed; 19.0 %).Results: The structure of the complications was as follows. 1. The group of intraoperative complications included: spasm of the ICA, cerebral arteries — 4 cases (1.3 %), acute cardio-respiratory manifestations and hemodynamic instability — 93 (29.7 %). 2. Group of general complications: cerebrovascular accident — 3 cases (0.9 %), hematological toxicity — 14 (4.5 %). 3. Group of local complications. A) External extraocular manifestations: transient eyelid edema — 49 (15.7 %), frontal arteritis — 2 (0.6 %), ptosis of the upper eyelid — 11 (3.5 %), ptosis and deviation of the eyeball — 2 ( 0.6 %), soft tissue necrosis — 1 (0.3 %). B) Intraocular manifestations: retinal detachment — 13 (4.2 %), chorioretinal atrophy — 4 (1.2 %), edema of the optic nerve head — 2 (0.6 %), atrophy of the optic nerve head — 1 (0.3 %), hemophthalmia — 3 (0.9 %).Conclusion: Modern interventional endovascular methods allow to carry out the SOAI safety and reduce the number of possible complications.

Intraoperative Identification of the Shunt Point of Spinal Arteriovenous Malformations by a Selective Arterial Injection of Saline to Subtract Signals of Indocyanine Green: Technical Note

It is crucial to identify a shunt point for spinal arteriovenous malformation (AVM) treatment. For this purpose, some intraoperative supports have been reported-intravenous injection of indocyanine green (ICG), selective arterial injection of ICG, and selective arterial injection of saline with a high frame rate digital camera. However, there are difficulties in accurately identifying the shunt point, especially if the lesion has multiple feeders. The aim of this technical note was to report a novel method, selective arterial injection of saline to subtract signals of ICG, to precisely identify perimedullary arteriovenous fistula shunt points having multiple feeding arteries. After exposing the lesion, a 4-F catheter was cannulated into the origins of the segmental artery. ICG was injected intravenously as a first step, and then heparinized saline solution was flushed from the catheter. Compared with other methods, this method could identify the exact shunt point and was effective for certain shunt point obliterations. Despite having similar invasiveness, selective arterial injection of saline to subtract signals of ICG is superior to previously described techniques, such as selective arterial injection of ICG. Therefore, it will be useful in spinal arteriovenous malformation surgical treatment.

Thromboxane A 2 Receptors Contribute to the Exaggerated Exercise Pressor Reflex in Rats with Heart Failure

Background Mechanical and metabolic signals associated with skeletal muscle contraction stimulate the sensory endings of thin fiber skeletal muscle afferents. During exercise, stimulation of these afferents initiates a reflex, termed the exercise pressor reflex (EPR), which contributes importantly to reflex increases in sympathetic nerve activity (SNA) and mean arterial blood pressure (MAP). In patients and animals with heart failure with reduced ejection fraction (HF-rEF), activation of the EPR contributes to exaggerated increases in SNA and is linked to decreased exercise tolerance and increased mortality. The exaggerated EPR in HF-rEF is attributed, at least in part, to an increased responsiveness of thin fiber skeletal muscle afferents produced by cyclooxygenase (COX) products of arachidonic metabolism. However, the COX metabolite receptors on the sensory endings that mediate the COX-induced afferent sensitization in HF-rEF are unknown. Purpose & Hypothesi The purpose of this investigation was to determine the role played by one of the major receptors for products of COX metabolism present on sensory neurons, namely thromboxane A2 receptors (TxA2-Rs), in the exaggerated EPR in HF-rEF rats. We tested the hypothesis that injection of the TxA2-R antagonist daltroban (80μg) into the arterial supply of the hindlimb would reduce the reflex increase in renal SNA (RSNA) and MAP evoked in response to 30 seconds of 1 Hz dynamic hindlimb muscle contraction in HF-rEF rats, but not control rats. Methods Experiments were performed on male Sprague-Dawley rats subjected to either a coronary artery ligation surgery to produce myocardial infarction and HF-rEF or a sham ligation. At least six weeks after the initial surgery, in decerebrate, unanesthetized rats we compared the EPR evoked by electrically induced hindlimb skeletal muscle contraction before and after injection of daltroban into the arterial supply of the hindlimb. Results Ejection fraction was significantly reduced in HF-rEF (47±3%) compared to sham (84±1%, p<0.01). We found that daltroban reduced the EPR response in HF-rEF (n=8; peak ΔMAP pre: 17±4; post: 12±2mmHg; P=0.04; peak ΔRSNA pre: 135±55; post: 46±13%; P=0.07), but not in SHAM rats (n=10; peak ΔMAP pre: 13±3; post: 11±2mmHg; P=0.48; peak ΔRSNA pre: 64±17; post: 63±15%; P=0.96;) rats. In a separate group of HF-rEF rats (n=4), we determined whether systemic circulation of daltroban accounted for the attenuating effects on EPR activation seen when daltroban was injected into the hindlimb arterial supply. We found that intravenous injection of daltroban had no effect on the EPR (peak ΔMAP pre: 26±7; post: 25±7mmHg; P=0.50). In these same four HF-rEF rats we also found that hindlimb arterial injection of the vehicle for daltroban (0.4mL saline containing 1% DMSO) had no effect on the EPR (peak ΔMAP pre: 23±8; post: 20±6mmHg; P=0.40). Conclusions These data suggest that that TxA2-R receptors on the sensory endings of muscle afferents contribute to the exaggerated EPR in HF-rEF. Our data enhance the understanding of the sympathetic and cardiovascular adjustments to exercise in the ~6 million Americans with HF-rEF.

TRPV1 Channel Stimulation Reduces the Mechanoreflex in Decerebrate Rats

Background Mechanically-sensitive channels (MSCs) located on group III and IV thin fiber skeletal muscle afferents are stimulated by skeletal muscle contraction during exercise and contribute to reflex increases in sympathetic nervous system activity and blood pressure. This exercise-induced mechanically activated reflex, termed the mechanoreflex, is dependent on MSC stimulation produced by changes in muscle length and concurrent increases in intramuscular pressure during contraction. A relatively novel class of mechanically activated channel known as “piezo” is thought to contribute importantly to the generation of the mechanoreflex. For example, we found recently that hindlimb arterial injection of GsMTx4, a partially selective piezo channel inhibitor, reduced the pressor response to isolated dynamic mechanoreflex activation in rats. Recent work on the gating mechanics of piezo channels reveal that their activation can be regulated by changes in the phospholipid components of the cell membrane. Stimulation of transient receptor potential vanilloid 1 (TRPV1) has been shown to alter membrane concentrations of phospholipid component phosphatidylinositol 4,5-bisphosphate (PIP2). Specifically, stimulation of TRPV1 by capsaicin has been shown to completely inhibit piezo channel currents by depleting PIP2 in dorsal root ganglia neurons. Whether TRPV1 stimulation with capsaicin can modulate MSCs involved in mechanoreflex activation and reduce the reflex increase in blood pressure during dynamic hindlimb muscle stretch remains unknown. Purpose and Hypothesis Our purpose was to investigate the effect of TRPV1 stimulation produced by the injection of capsaicin into the arterial supply of the hindlimb on the mechanoreflex in healthy rats with patent femoral arteries (“freely perfused”, FP) and in a chronically ligated femoral artery rat model of simulated peripheral artery disease (“ligated”) in which the mechanoreflex is exaggerated. We tested the hypothesis that hindlimb arterial injection of capsaicin would reduce the pressor response to 30 s of 1 Hz dynamic hindlimb muscle stretch in both FP and ligated rats. Methods We compared (paired Student's t-tests) the pressor response (peak Δ mean arterial blood pressure) to muscle stretch before and 30 minutes after the injection of the TRPV1 agonist capsaicin (0.5 µg in 0.25ml) into the arterial supply of the hindlimb circulation of decerebrate, unanesthetized rats. Results Injection of capsaicin into the arterial supply of the hindlimb produced a pressor response in 57±14 mmHg in FP rats and 52±4 mmHg in ligated rats. More importantly, we found that capsaicin significantly reduced the peak pressor response to dynamic stretch in both FP (n=4, pre: 19±5, post: 5±1 mmHg, p=0.04) and ligated (n=7, pre: 27±3, post: 19±4 mmHg, p=0.01) rats. Conclusion We conclude that TRPV1 stimulation with capsaicin reduced the mechanoreflex evoked by dynamic stretch in both FP and ligated rats. These data provide additional, albeit indirect, evidence that piezo channels contribute importantly to the generation of the mechanoreflex and that TRPV1 stimulation-induced desensitization of piezo channels is capable of modulating mechanoreflex activation.

Localization and Maintenance of Engrafted Mesenchymal Stem Cells Administered via Renal Artery in Kidneys with Ischemia-Reperfusion Injury.

Mesenchymal stem cells (MSCs) are a potential therapeutic tool for preventing the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). Herein, we investigated the localization and maintenance of engrafted human bone marrow-derived MSCs in rats subjected to a renal ischemia-reperfusion injury (IRI) and compared the effectiveness of two intravascular injection routes via the renal artery or inferior vena cava. Renal artery injection of MSCs was more effective than intravenous injection at reducing IRI-induced renal fibrosis. Additionally, MSCs injected through the renal artery persisted in injured kidneys for over 21 days, whereas MSCs injected through the inferior vena cava survived for less than 7 days. This difference may be attributed to the antifibrotic effects of MSCs. Interestingly, MSCs injected through the renal artery were localized primarily in glomeruli until day 3 post-IRI, and they decreased in number thereafter. In contrast, the number of MSCs localized in tubular walls, and the interstitium increased gradually until day 21 post-IRI. This localization change may be related to areas of damage caused by IRI because ischemia-induced AKI leads to tubular cell damage. Taken together, these findings suggest renal artery injection of MSCs may be useful for preventing the progression of AKI to CKD.

Polymer stealthing and mucin-1 retargeting for enhanced pharmacokinetics of an oncolytic vaccinia virus

Vaccinia virus (VV) is a powerful tool for cancer treatment with the potential for tumor tropism, efficient cell-to-cell spread, rapid replication in cancer cells, and stimulation of anti-tumor immunity. It has a well-defined safety profile and is being assessed in late-stage clinical trials. However, VV clinical utility is limited by rapid bloodstream neutralization and poor penetration into tumors. These factors have often restricted its route of delivery to intratumoral or intrahepatic artery injection and may impede repeat dosing. Chemical stealthing improves the pharmacokinetics of non-enveloped viruses, but it has not yet been applied to enveloped viruses such as VV. In the present study, amphiphilic polymer was used to coat VV, leading to reduced binding of a neutralizing anti-VV antibody (81.8% of polymer-coated VV [PCVV] staining positive versus 97.1% of VV [p = 0.0038]). Attachment of anti-mucin-1 (aMUC1) targeting antibody, to give aMUC1-PCVV, enabled binding of the construct to MUC1. In high MUC1 expressing CAPAN-2 cells, infection with PCVV was reduced compared to VV, while infection was restored with aMUC1-PCVV. Pharmacokinetics of aMUC1-PCVV, PCVV, and VV were evaluated. After intravenous (i.v.) injection of 1 × 108 viral genomes (VG) or 5 × 108 VG, circulation time for PCVV and aMUC1-PCVV was increased, with ~5-fold higher circulating dose at 5 min versus VV.