Expression of transport proteins in the rete mirabile of european silver and yellow eel

Background In physoclist fishes filling of the swimbladder requires acid secretion of gas gland cells to switch on the Root effect and subsequent countercurrent concentration of the initial gas partial pressure increase by back-diffusion of gas molecules in the rete mirabile. It is generally assumed that the rete mirabile functions as a passive exchanger, but a detailed analysis of lactate and water movements in the rete mirabile of the eel revealed that lactate is diffusing back in the rete. In the present study we therefore test the hypothesis that expression of transport proteins in rete capillaries allows for back-diffusion of ions and metabolites, which would support the countercurrent concentrating capacity of the rete mirabile. It is also assumed that in silver eels, the migratory stage of the eel, the expression of transport proteins would be enhanced. Results Analysis of the transcriptome and of the proteome of rete mirabile tissue of the European eel revealed the expression of a large number of membrane ion and metabolite transport proteins, including monocarboxylate and glucose transport proteins. In addition, ion channel proteins, Ca2+-ATPase, Na+/K+-ATPase and also F1F0-ATP synthase were detected. In contrast to our expectation in silver eels the expression of these transport proteins was not elevated as compared to yellow eels. A remarkable number of enzymes degrading reactive oxygen species (ROS) was detected in rete capillaries. Conclusions Our results reveal the expression of a large number of transport proteins in rete capillaries, so that the back diffusion of ions and metabolites, in particular lactate, may significantly enhance the countercurrent concentrating ability of the rete. Metabolic pathways allowing for aerobic generation of ATP supporting secondary active transport mechanisms are established. Rete tissue appears to be equipped with a high ROS defense capacity, preventing damage of the tissue due to the high oxygen partial pressures generated in the countercurrent system.

P.191 Development and Testing of a Novel Hydrogel Embolization Treatment for Neurovascular Diseases: Preliminary Animal Results

Background: Embolization represents a minimally invasive treatment modality for arteriovenous malformations (AVMs), tumors, aneurysms, and vessel sacrifice, but can be limited by currently available embolization agents. Discovery of new and improved agents could lead to better treatment outcomes. The goal of this project was to develop and test a novel embolization agent using hydrogels, a class of materials which may be bioengineered to suit a variety of indications. Methods: We devised a method of liquid hydrogel embolization with photo-modulated crosslinking for intravascular solidification, using a custom microcatheter set-up. We tested this in swine blood vessels (n=3), the swine renal arterial trees as a vascular tumor model (n=5), and the swine arterial-arterial networks of the rete mirabile as an AVM model (n=3). Hydrogel embolization was assessed for treatment efficacy and safety. Follow-up angiography was performed at 2-4 week intervals. Results: Hydrogel embolization was technically successful in all animals, with full occlusion of the vascular target immediately following embolization and at follow-up. There were no instances of clinical or angiographic complications. Conclusions: We demonstrated a novel method of dynamic photomodulation and delivery of bioengineered hydrogels to address current limitations of endovascular embolization therapies. This promising technology will be investigated further with longer-term comparative animal trials.

Abstract 1122‐000236: Intravascular Delivery and Crosslinking of Photosensitive Hydrogels for Embolizing Animal Models of AVMs and Tumors

Introduction : Embolization represents a minimally invasive treatment modality for arteriovenous malformations (AVMs), tumors, and other indications, but can be limited by currently available embolic agents, in terms of safety and efficacy. Discovery of new and improved agents could lead to better treatment outcomes. The goal of this project was to test a novel embolization methodology for the treatment of AVMs and tumors. Methods : We formulated low‐viscosity, shear‐thinning hydrogel formulations which were mixed with a photo‐initator agent and non‐ionic contrast medium. We then developed a method of intravascular hydrogel delivery with photo crosslinking at the tip of the catheter, using an integrated optical fibre. This allowed for rapid transition from a low viscosity liquid to a crosslinked solid‐state hydrogel to block blood flow to the vascular target. In addition, the UV intensity can be dynamically modulated, in real‐time, to modify the degree of crosslinking and thus the viscosity of the embolic agent. We utilized the swine rete mirabile as an animal model for AVMs, and the swine renal arterial tree (inferior segmental artery) as a model for hypervascular tumors. 5 animals were utilized without prior preparation. Embolization was graded based on degree of complete obliteration of the rete nidus or the renal arterial tree. Any non‐target embolization or other complications were recorded. Follow‐up angiography was performed at the 4‐week interval. Results : With a combination of shear‐thinning properties and dynamic modulation of photo crosslinking, we show that we are able to deliver an embolic agent with a viscosity range of up to 10^4 Pa*s through a single low viscosity precursor that is injectable through microcatheters (Figure 1). Using this methodology, hydrogel embolization was technically successful in all animals. Following embolization, 4/5 rete mirabile and 5/5 inferior renal arterial trees were completely obliterated. Representative angiographic images are shown in Figures 2 and 3. There were no instances of clinical or angiographic complications. Conclusions : We demonstrated a novel method of intravascular delivery of low viscosity photosensitive hydrogels, with photo crosslinking at the tip of the catheter, to successfully embolize animal models for AVMs and tumors. This promising technology will be investigated further with longer‐term comparative animal trials.

Vascular Effects of Pseudoxanthoma Elasticum

Background: Pseudoxanthoma elasticum (PXE) is a rare hereditary disease caused by mutations in the ABCC6 gene, characterized by ectopic calcification of connective tissue throughout the body. Vascular conditions associated with PXE have been well-documented in the literature, but to our knowledge, analysis of the myriad of PXE case reports with associated vascular diseases in addition to larger cohort studies, has not been undertaken. Objective: To review existing literature reporting peripheral vascular disease (PVD), cardiovascular disease (CVD), cerebrovascular disease (CeVD), hypertension, and carotid rete mirabile (CRM) in PXE patients as of June 2021. Methods: A search of the PubMed database using the key words “pseudoxanthoma elasticum” and “vascular” was performed. Results: A total of 345 cases of PVD, 97 cases of CVD, and 123 case of CeVD were reported. Additionally, 88 cases of hypertension and 5 cases of CRM were reported. Conclusions: PXE patients are at risk of developing serious vascular conditions, particularly peripheral vascular disease. This condition also appears to have some connection to carotid rete mirabile, which is extremely rare in humans. Further research should be conducted to analyze the connection between PXE and CRM in order to better understand and treat both conditions.

The rostral epidural rete mirabile of the llama as a place of retrograde transport of various substances – anatomical basics

The aim of this study was to analyse the structure of the rostral epidural rete mirabile in the llama. Some specimens were prepared by injecting stained chemically cured acrylic into the bilateral common carotid arteries. After about 1 month received vascular corrosion casts on the bone scaffold. Some specimens made using red and blue latex introduced into the bilateral common carotid arteries and the bilateral external jugular vein. The rostral epidural rete mirabile is a well-developed, bilateral structure composed of numerous arteries, which are multiply anastomosed with each other. The cranial section of the rete is asymmetrical. Its lateral part is much better developed, because there are rostral branches to the rostral epidural rete mirabile at this point. The arterial vessels are not accompanied by homonymous veins. However, the arteries of the rostral epidural rete mirabile are accompanied by venous vessels of the cavernous sinus. That rete plays an important role in selective brain cooling, the conservation of body water, and retrograde transport of neurotransmitters. CO, GnRH, beta-endorphin, progesterone, testosterone, oxytocin, LHRH and dopamine diffuse from the venous blood of the cavernous sinus to the arterial blood of the rostral epidural rete mirabile.

Histologic Examination of a Sea Pig (Scotoplanes sp.) Using Bright Field Light Microscopy

Sea pigs (Scotoplanes spp.) are deep-sea dwelling sea cucumbers of the phylum Echinodermata, class Holothuroidea, and order Elasipodida. Few reports are available on the microscopic anatomy of these deep-sea animals. This study describes the histologic findings of two, wild, male and female Scotoplanes sp. collected from Monterey Bay, California. Microscopic findings were similar to other holothuroids, with a few notable exceptions. Sea pigs were bilaterally symmetrical with six pairs of greatly enlarged tube feet arising from the lateral body wall and oriented ventrally for walking. Neither a rete mirabile nor respiratory tree was identified, and the large tube feet may function in respiration. Dorsal papillae protrude from the bivium and are histologically similar to tube feet with a large, muscular water vascular canal in the center. There were 10 buccal tentacles, the epidermis of which was highly folded. Only a single gonad was present in each animal; both male and female had histologic evidence of active gametogenesis. In the male, a presumed protozoal cyst was identified in the aboral intestinal mucosa, and was histologically similar to previous reports of coccidians. This work provides control histology for future investigations of sea pigs and related animals using bright field microscopy.

Did Andreas Vesalius’s De Humani Corporis Fabrica and/or Juan Valverde’s Historia De La Composicion Del Cuerpo Humano Really Influence the Anatomy Knowledge in the Ottoman Empire? A Preliminary Study on Shams al-Dīn ʿItāqī’s Tashrīh al-Abdān*

Aim of this study was to determine whether Vesalius and Valverde influenced Shams al-Dīn ʿItāqī considering the figures and several statements in Tashrīḥ al-Abdān wa Tarjamān Qibāla Faylasūfān. The statements and figures in illustrated copies of ʿItāqī’s book were examined and compared to those in Galen’s, Avicenna’s, Vesalius’s, and Valverde’s works, then the findings were evaluated. ʿItāqī’s book contains some figures only from Vesalius and/or Valverde’s works, but there is no new explanation related to issues such as the mandible, the sacrum, the rete mirabile, and the uterus. The Latin edition of Valverde’s book published in 1607 was probably the source of the Western-originated illustrations in the manuscript Hüsrev Paşa, Nr. 464 and of all the Western-based illustrations, except for the female figure in the manuscript of Istanbul University, Turkish Manuscripts, TY 2662. Spanish and/or Italian and/or Latin (1589) editions of Valverde’s book were the sources of most of the Western-originated illustrations, except the human skeleton figure in the manuscript of Prof. Uzluk’s personal collection. The information given by the works of Vesalius and Valverde has not influenced the explanations of ʿItāqī. ʿItāqī wrote his book according to the classical anatomical knowledge in the Islamic world of his era and he added Eastern- and Western-originated figures to his book to support/strengthen his statements. Or ʿItāqī work Tasrīḥ al-Abdān originally contained no illustrations. However, later, scribes/copiers added Eastern- and Western-originated anatomical figures to the book to support/strengthen statements at different times.

Abstract P495: Aqua Embolic System: Evaluating the Performance of a New Liquid Embolic System Using a Swine AVM Model

Introduction: Liquid embolic material (LEM) plays an essential role in the treatment of hemorrhagic stroke caused by vascular malformation such as arteriovenous malformations (AVMs). However, currently available non-adhesive LEMs has the problem of catheter entrapment, and also known to have cytotoxicity due to the organic solvents such as Dimethyl Sulfoxide (DMSO). Aqua Embolic System (AES) is a new liquid embolic material, which is mainly composed of multiple polysaccharides. AES, when injected via a microcatheter, immediately forms a solid and elastic hydrogel cast upon exposure to Ca2+ in the bloodstream. The use of organic solvents, e.g., DMSO, is not required. The performance of AES was evaluated using an established AVM model utilizing swine rete-mirabile. Methods: Under general anesthesia, the left ascending pharyngeal artery (APA) of Yorkshire swine (40 kg) was catheterized using a microcatheter (ID:0.013 inches), and AES was slowly injected into the rete-mirabile under fluoroscopy. The following parameters were assessed to evaluate the embolization performance of the AES; 1) the amount of AES required for the complete occlusion of the feeding artery, 2) injection speed, 3) radiopacity during the deployment, and 4) incidence of catheter entrapment after the injection. The same evaluation was performed on the contralateral rete-mirabile and the left renal artery as well. Results: 12 arteries in 4 swine were treated, and all arteries were completely occluded without technical complications. The injected materials immediately formed AES cast in all vessels, followed by the reflux over the tip of the microcatheter. All catheters were withdrawn without any sign of catheter entrapment. The AES mixed with tantalum based contrasts medium showed sufficient radiopacity under fluoroscopy. With the injection speed of 0.02ml/sec, the average volume required was 0.85mL for the APA and 2.9mL for the renal artery. No increased thrombogenicity or vasospasm near the treated lesion was observed during the procedure. Conclusions: AES, which is a DMSO free, non-adhesive polysaccharides-based LEM, may be used as an embolic material for the treatment of hemorrhagic stroke caused by cerebrovascular diseases, such as brain AVM.

Liquid embolic agent Fe3O4-EVOH for endovascular arteriovenous malformation embolisation: Preliminary evaluation in an in vivo swine rete mirabile model

Aim Arteriovenous malformation (AVM) embolisation is in peril after the ARUBA trial. Advancements that are needed to reduce procedural risk are better control and visualisation during micro-catheter injection of liquid embolic material. The injectability, radiographic visualisation, mechanical stability and biocompatibility of the embolic agent Fe3O4-EVOH was evaluated in an in vivo swine AVM model. Methods The swine AVM model is the rete mirabile (RM). Nine swine AVM models were embolised with the embolic agent Fe3O4-EVOH by using a 1.5 F micro-catheter. Procedure times, embolisation success (defined as complete embolisation of the nidus), volume of embolic agent and histopathology were assessed. Results Six swine underwent embolisation of one side rete, and three underwent embolisation of both sides. We did not experience any technical complication during embolisation of each rete. The micro-catheter was easy to retrieve. Fluoroscopic visualisation of the Fe3O4-EVOH cast was adequate. The mean embolisation time for each RM was 7.5 minutes. The median volume of the embolic agent for each RM was 0.52 mL. At one, four and eight weeks following injection, microscopic and histological analysis demonstrated minimal inflammatory changes in the perivascular tissues and permanent occlusion of the embolised vasculature. Conclusion Fe3O4-EVOH embolic agent is an effective endovascular occlusion material, providing the initial in vivo characteristics of stability and biocompatibility.