Modeling Robotic-Assisted Mechanical Thrombectomy Procedures with the CorPath GRX Robot: The Core-Flow Study.

BACKGROUND AND PURPOSE: Endovascular robotic devices may enable experienced neurointerventionalists to remotely perform endovascular thrombectomy. This study aimed to assess the feasibility, safety, and efficacy of robot-assisted endovascular thrombectomy compared with manual procedures by operators with varying levels of experience, using a 3D printed neurovascular model. MATERIALS AND METHODS: M1 MCA occlusions were simulated in a 3D printed neurovascular model, linked to a CorPath GRX robot in a biplane angiography suite. Four interventionalists performed manual endovascular thrombectomy (n = 45) and robot-assisted endovascular thrombectomy (n = 37) procedures. The outcomes included first-pass recanalization (TICI 2c-3), the number and size of generated distal emboli, and procedural length. RESULTS: A total of 82 experimental endovascular thrombectomies were conducted. A nonsignificant trend favoring the robot-assisted endovascular thrombectomy was observed in terms of final recanalization (89.2% versus manual endovascular thrombectomy, 71.1%; P = .083). There were no differences in total mean emboli count (16.54 [SD, 15.15] versus 15.16 [SD, 16.43]; P = .303). However, a higher mean count of emboli of > 1 mm was observed in the robot-assisted endovascular thrombectomy group (1.08 [SD, 1.00] versus 0.49 [SD, 0.84]; P = .001) compared with manual endovascular thrombectomy. The mean procedural length was longer in robot-assisted endovascular thrombectomy (6.43 [SD, 1.71] minutes versus 3.98 [SD, 1.84] minutes; P < .001). Among established neurointerventionalists, previous experience with robotic procedures did not influence recanalization (95.8% were considered experienced; 76.9% were considered novices; P = .225). CONCLUSIONS: In a 3D printed neurovascular model, robot-assisted endovascular thrombectomy has the potential to achieve recanalization rates comparable with those of manual endovascular thrombectomy within competitive procedural times. Optimization of the procedural setup is still required before implementation in clinical practice.

Increased Number of Passes and Double Stent Retriever Technique Induces Cumulative Injury on Arterial Wall After Mechanical Thrombectomy in a Swine Model.

The number of stentriever passes during endovascular thrombectomy impacts clinical outcomes in acute ischemic stroke. Previous studies suggest that the simultaneous double stent retriever technique (DSRT) could improve the efficacy and reduce the number of passes. We aim to analyze the degree of vessel wall injury according to the number of passes and technique (single vs. simultaneous devices). Histological changes were evaluated in renal arteries (RAs) of swine models after thrombectomy (1, 2, or 3 passes) with single stent (SSRT) and DSRT. Thrombectomy passes were performed in 12 RA: 3 samples from each artery were studied by optical microscopy to assess a vascular damage score. All thirty-six samples showed endothelial denudation and different degrees of damage in the deepest layers of the arterial wall; however, all arteries remained patent by the time of assessment. In all cases, the degree of vascular injury increased with the number of passes. Compared with a SSRT, DSRT showed a higher severity of histological damage corresponding to the damage caused by 1.4 SSRT passes. However, in distal arteries, vascular damage was relatively similar when comparing SSRT with multiple passes and DSRT with one pass. The degree of vessel injury increases with the number of passes. Even though histological damage per pass was 1.4 higher with DSRT than SSRT, short-term vessel patency was not compromised after up to 3 DSRT passes. Further studies are needed to characterize the risk-benefit ratio of the DSRT in routine clinical practice.

Surgical options in experimental porcine model for endovascular training in complex vascular lesions.

We describe a new, elegant, two-phase, microsurgical method that minimizes the surgical preparation time for different complex vascular lesions in a swine model. In the first phase, the model is prepared microsurgically in the experimental laboratory using arterial or/and venous grafts. In the second phase, the model is implanted in the experimental animal. This two-fold method allows for increasing the complexity and accuracy of the model while reducing preparation time on the day of the training session.

Use of an acellular collagen-elastin matrix to support bladder regeneration in a porcine model of peritoneocystoplasty.

INTRODUCTION: Bladder reconstruction without using the intestine remains a challenge to this day despite the development of new biomaterials and cell cultures. Human bladder engineering is merely anecdotic, and mostly in vitro and animal studies have been conducted. MATERIAL AND METHODS: In our study using a porcine model, we performed a bladder augmentation using an autologous parietal peritoneum graft (peritoneocystoplasty) and determined whether the attachment of an acellular collagen-elastin matrix (Group 1) or lack of (Group 2) had better histologic and functional results. Thus far, peritoneocystoplasty has rarely been performed or combined with a biomaterial. RESULTS: After 6 weeks, we observed different degrees of retraction of the new bladder wall in both groups, although the retraction was lower and the histological analysis showed more signs of regeneration (neoangiogenesis and less fibrosis) in Group 1 than when compared with Group 2. No transitional cells were found in the new bladder wall in any of the groups, and no differences were observed in the functional test results. CONCLUSIONS: Performing a peritoneocystoplasty is an easy and safe procedure. The data supports the benefit of an acellular collagen-elastin matrix to reinforce bladder regeneration. However, in our study we observed too much retraction of the new wall and the histologic results were not acceptable to consider it an appropriate cystoplasty technique.

Malignant infarction of the middle cerebral artery in a porcine model. A pilot study.

BACKGROUND AND PURPOSE: Interspecies variability and poor clinical translation from rodent studies indicate that large gyrencephalic animal stroke models are urgently needed. We present a proof-of-principle study describing an alternative animal model of malignant infarction of the middle cerebral artery (MCA) in the common pig and illustrate some of its potential applications. We report on metabolic patterns, ionic profile, brain partial pressure of oxygen (PtiO2), expression of sulfonylurea receptor 1 (SUR1), and the transient receptor potential melastatin 4 (TRPM4). METHODS: A 5-hour ischemic infarct of the MCA territory was performed in 5 2.5-to-3-month-old female hybrid pigs (Large White x Landrace) using a frontotemporal approach. The core and penumbra areas were intraoperatively monitored to determine the metabolic and ionic profiles. To determine the infarct volume, 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry analysis was performed to determine SUR1 and TRPM4 expression. RESULTS: PtiO2 monitoring showed an abrupt reduction in values close to 0 mmHg after MCA occlusion in the core area. Hourly cerebral microdialysis showed that the infarcted tissue was characterized by reduced concentrations of glucose (0.03 mM) and pyruvate (0.003 mM) and increases in lactate levels (8.87mM), lactate-pyruvate ratio (4202), glycerol levels (588 µM), and potassium concentration (27.9 mmol/L). Immunohistochemical analysis showed increased expression of SUR1-TRPM4 channels. CONCLUSIONS: The aim of the present proof-of-principle study was to document the feasibility of a large animal model of malignant MCA infarction by performing transcranial occlusion of the MCA in the common pig, as an alternative to lisencephalic animals. This model may be useful for detailed studies of cerebral ischemia mechanisms and the development of neuroprotective strategies.

Surgical Trauma Caused by Different Abdominal Access Routes-Comparison of Open Surgical, Laparoscopic, and NOTES Transgastric Techniques in a Porcine Model.

BACKGROUND: Investigations indicate that natural orifice translumenal endoscopic surgery (NOTES) procedures induce a less pronounced postoperative inflammatory response than open or laparoscopic surgery, inflicting less trauma. In NOTES procedures, no skin incision is performed. We compare the inflammatory response added by the type of incision by measuring C-reactive protein (CRP) and tumors necrosis factor-alfa (TNF-α). METHODS: Twenty-seven pigs were randomized to open surgical, laparoscopic, or transgastric NOTES abdominal access. After completion of the accesses, no surgery was performed. All accesses were left open for 40 minutes followed by closure, animals were survived for 7 days. Blood samples were drawn at the start of the accesses, at 20 and 40 minutes during the procedure, and at postoperative day (POD) 1, 3, and 7. Analyses of CRP and TNF-α were performed. RESULTS: CRP increased in all animals until POD1. This increase was greater in the open group (P = .006). No significant differences in CRP-levels were found at POD 1, 3, or 7. TNF-α showed a peak during the procedure, at 20 and 40 minutes, with normalization at POD1 for 1/3 of the open and laparoscopic animals, but not for the NOTES animals. Due to variations within the groups, no statistical difference was shown between them. At postmortem, 1/3 of the pigs in the laparoscopic and open groups had wound infections, while no NOTES animals showed infections. CONCLUSIONS: This study provides no statistically significant differences in inflammatory response after the different abdominal accesses. However, the lack of a TNF-α-peak in the NOTES group might indicate a less pronounced response, supporting the initial theories.

Teaching Chest Ultrasound in an Experimental Porcine Model.

OBJECTIVE: The objective of this study was to evaluate the efficacy of a short hands-on chest ultrasound course to detect normal lung pattern, pneumothorax (PTX), and pleural effusion (PE) in a porcine animal model. METHODS: Thirty-six trainees with no previous experience in chest ultrasound participated in the study. A 1.5-hour training course covering both theory and practice was developed. All static and dynamic signs of the normal lung parenchyma, PTX, and PE were analyzed. Four pigs were used. Approval by the local institutional animal care was obtained. An 8F drainage catheter was inserted into the pleural cavity under general anesthesia for injection of air or saline solution. A Vivid Q ultrasound with a 12L-RS linear probe was used. A baseline preintervention evaluation and 2 postintervention evaluations (one after theoretical class and the other after additional training with the animal model) were made. Sensitivity and specificity with the 95% confidence interval for recognition of the 3 patterns were analyzed, and results were compared with those obtained in the preintervention evaluation. RESULTS: All normal lung signs were detected, as these were signs of PE and PTX. Participants were able to diagnose a normal pattern (sensitivity, 100% [90%-100%]; specificity, 90% [84%-95%]), PE (sensitivity, 89% [75%-95%]; specificity, 95% [89%-98%]), and PTX (sensitivity, 82% [72%-89%]; specificity, 97% [90%-99%]) after 30 minutes of class and normal pattern (sensitivity, 95% [85%-98%]; specificity, 95% [85%-98%]), PE (sensitivity, 100% [88%-100%]; specificity, 98% [94%-99%]), and PTX (sensitivity, 90% [73%-96%]; specificity, 98% [92%-99%]) in the animal model. CONCLUSIONS: The porcine model is useful for ultrasound examination of the lung parenchyma and detection of pleural disease. Its use in the experimental laboratory is a major refinement that enables trainees to identify acute pulmonary complications.

An ultrasound-guided technique for axillary brachial plexus nerve block in rabbits.

Regional anesthesia techniques, such as nerve blocks, are routinely used in humans and can contribute to multimodal approaches to pain management in research animals. Ultrasound guidance is an emerging aspect of regional anesthesia that has the potential to optimize local delivery and distribution of anesthetic agents, thereby reducing the amounts of these agents that must be administered. The authors developed an ultrasound-guided technique for effective block of the axillary brachial plexus in rabbits. They used this technique to carry out nerve block in 14 rabbits. The procedure was accomplished in a relatively short amount of time and achieved successful nerve block in all rabbits with no adverse effects. Sonographic visualization of the distribution of the local anesthetic ropivacaine led to administration of smaller anesthetic doses in eight of the rabbits without affecting the duration of nerve block. The authors conclude that their technique is feasible and safe and provides effective analgesia of the thoracic limb in rabbits. They recommend that this technique be integrated into multimodal approaches to pain management in rabbits undergoing thoracic limb surgery.

Single intracoronary injection of encapsulated antagomir-92a promotes angiogenesis and prevents adverse infarct remodeling.

BACKGROUND: Small and large preclinical animal models have shown that antagomir-92a-based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR-92a inhibition in noncardiac organs prevents the translation of nonvectorized miR-targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir-92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction AUTHOR: Should "acute" be added before "myocardial infarction" (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects. METHODS AND RESULTS: In a percutaneous pig model of reperfused AMI, a single intracoronary administration of antagomir-92a encapsulated in specific microspheres (9 µm poly-d,-lactide-co-glycolide [PLGA]) inhibited miR-92a in a local, selective, and sustained manner (n=3 pigs euthanized 1, 3, and 10 days after treatment; 8×, 2×, and 5×-fold inhibition at 1, 3, and 10 days). Downregulation of miR-92a resulted in significant vessel growth (n=27 adult minipigs randomly allocated to blind receive encapsulated antagomir-92a, encapsulated placebo, or saline [n=8, 9, 9]; P=0.001), reduced regional wall-motion dysfunction (P=0.03), and prevented adverse remodeling in the infarct area 1 month after injury (P=0.03). Intracoronary injection of microspheres had no significant adverse effect in downstream myocardium in healthy pigs (n=2), and fluorescein isothiocyanate albumin-PLGA microspheres were not found in myocardium outside the left anterior descending coronary artery territory (n=4) or in other organs (n=2). CONCLUSIONS: Early single intracoronary administration of encapsulated antagomir-92a in an adult pig model of reperfused AMI prevents left ventricular remodeling with no local or distant adverse effects, emerging as a promising therapeutic approach to translate to patients who suffer a large AMI.

Single-Access Fetal Endoscopy (SAFE) for myelomeningocele in sheep model I: amniotic carbon dioxide gas approach.

BACKGROUND: This study aimed to assess the feasibility of single-access fetal endoscopy (SAFE) for the management of myelomeningocele (MMC) using intrauterine carbon dioxide as a distension medium in a sheep model. METHODS: This prospective experimental case-control study investigated 12 lamb fetuses that had a myelomeningocele-like defect surgically created on the 75th day of gestation. Four fetuses remained untreated (control group), and eight fetuses had MMC repair using two fetoscopic approaches with carbon dioxide used to distend the amniotic cavity. A collagen patch was placed over the defect and secured with surgical sealant. Four animals had a two-port fetoscopic procedure, and four animals had SAFE. Clinical and pathologic studies were performed after delivery. RESULTS: This study confirmed the validity of the animal MMC model. None of the control animals was able to stand or walk, and all had a significant defect in the lumbar area with continuous leakage of cerebrospinal fluid, ventriculomegaly, and a Chiari-II malformation. All the treated animals, independently of the number of ports used in the repair, were able to walk and had a closed defect with resolution of the Chiari malformation. CONCLUSIONS: The SAFE patch and glue coverage of surgically created fetal MMC is feasible and effective in restoring gross neurologic function in the fetal lamb model.

The receptor tyrosine kinase EPHB4 has tumor suppressor activities in intestinal tumorigenesis.

Colorectal cancer is the second cause of cancer-related death in the western world, and although the genetic and molecular mechanisms involved in the initiation and progression of these tumors are among the best characterized, there are significant gaps in our understanding of this disease. The role of EPHB signaling in colorectal cancer has only recently been realized. Here, we use animal models to investigate the role of EphB4 in intestinal tumorigenesis. Modulation of EPHB4 levels in colon cancer cell lines resulted in significant differences in tumor growth in a xenograft model, with low levels of EPHB4 associated with faster growth. In addition, using a genetic model of intestinal tumorigenesis where adenomatous polyposis coli (Apc) mutations lead to initiation of the tumorigenic process (Apc(min) mice), we show that inactivation of a single allele of EphB4 results in higher proliferation in both the normal epithelium and intestinal tumors, significantly larger tumors in the small intestine, and a 10-fold increase in the number of tumors in the large intestine. This was associated with a 25% reduction in the lifespan of Apc(min) mice (P < 0.0001). Gene expression analysis showed that EphB4 mutations result in a profound transcriptional reprogramming, affecting genes involved in cell proliferation, remodeling of the extracellular matrix, and cell attachment to the basement membrane among other functional groups of genes. Importantly, in agreement with the expression profiling experiments, using an in vitro assay, we show that loss of EPHB4 in colon cancer cells results in a significantly increased potential to invade through a complex extracellular matrix. Collectively, these results indicate that EphB4 has tumor suppressor activities and that regulation of cell proliferation, extracellular matrix remodeling, and invasive potential are important mechanisms of tumor suppression.

Cirugía endoscópica transluminal NOTES: resultados experimentales iniciales / Natural orifice transluminal endoscopic surgery (NOTES): initial experimental results

Introducción: La aparición de la cirugía endoscópica transorificial (NOTES) y de nuevos prototipos para su realización nos llevó a diseñar un programa de cirugía experimental. Material y métodos: Se ha realizado durante 1 año cirugía de NOTES en cerdas, cumpliendo la normativa europea de experimentación animal. Se han practicado 90 intervenciones sin supervivencia animal. En este estudio se ha evaluado: a) complejidad de las vías de acceso (transgástrica, transvaginal, transesofágica y transumbilical); b) técnicas de ayuda para la orientación temporoespacial, y c) posibilidades técnicas de cierre de los orificios viscerales (clips, t-bars®, clips de Obesco® y sutura por endoscopia). Las intervenciones practicadas mediante uno o dos endoscopios han sido: anexectomía, colecistectomía, biopsia de adenopatías mediastínicas, pancreatectomía distal y gastroyeyunostomía. Resultados: Esta experiencia nos ha permitido conocer una serie de aspectos técnicos imprescindibles para el desarrollo del NOTES: a) el neumoperitoneo con CO2 es más seguro para la entrada; b) el tamaño del orificio es importante para limitar la contaminación; c) la entrada con punción y dilatación con guía es más segura; d) la buena localización de la salida gástrica facilita el abordaje de las vísceras a disecar; e) la hemorragia intrabdominal es de difícil control; f) el cierre con garantías absolutas de fuga no existe, los clips no lo garantizan, los t-bars® y clips de Obesco® y la sutura endoscópica pueden funcionar, y g) la posibilidad de utilizar endoscopios que triangulan facilita la disección. Conclusiones: La NOTES requiere de un equipo multidisciplinario con cirujanos laparoscopistas y endoscopistas. La realización de NOTES pura es compleja; posiblemente las formas híbridas o la vía transumbilical sean fases intermedias (AU)

Introduction: The advent of natural orifice endoscopic surgery (NOTES) and new prototypes for performing this surgical procedure led us to design an experimental animal surgical programme. Material and method: NOTES was performed over a period of one year, in sows, following the European guidelines on the use of experimental animals. Ninety operations were performed with no animals surviving. The following aspects were assessed: 1. Access route complexity (transgastric, transvaginal, transesophageal and transumbilical). 2. Support measures for temporal/spatial orientation. 3. Technical possibilities for visceral orifice closure (clips, T-bars®, Obesco® clips and endoscopic suture). Resections of fallopian tubes, ovaries, gallbladder, mediastinal lymph nodes, tail of the pancreas and gastrojejunal derivations were performed with one or two endoscopes. Results: This experience enabled us to highlight a series of technical aspects essential for these techniques: 1. Pneumoperitoneum with CO2 is safer for entry. 2. Orifice size is important to limit contamination. 3. Puncture entry and guided dilation is safer. 4. Good gastric exit location makes it easier to approach viscera to be resected. 5. Intra-abdominal haemorrhage is difficult to control. 6. Leak-free closure cannot be guaranteed with clips, but t-bars® and Obesco® clips may be effective. 7. Endoscopes that permit triangulation may facilitate the dissection and endoscopic suture. Conclusions: NOTES requires a multidisciplinary team comprising laparoscopic and endoscopic surgeons. Pure NOTES is complex and hybrid forms or transumbilical route could be intermediate steps (AU)

[Natural orifice transluminal endoscopic surgery (NOTES): initial experimental results]. / Cirugía endoscópica transluminal NOTES: resultados experimentales iniciales.

INTRODUCTION: The advent of natural orifice endoscopic surgery (NOTES) and new prototypes for performing this surgical procedure led us to design an experimental animal surgical programme. MATERIAL AND METHOD: NOTES was performed over a period of one year, in sows, following the European guidelines on the use of experimental animals. Ninety operations were performed with no animals surviving. The following aspects were assessed: 1. Access route complexity (transgastric, transvaginal, transesophageal and transumbilical). 2. Support measures for temporal/spatial orientation. 3. Technical possibilities for visceral orifice closure (clips, T-bars, Obesco clips and endoscopic suture). Resections of fallopian tubes, ovaries, gallbladder, mediastinal lymph nodes, tail of the pancreas and gastrojejunal derivations were performed with one or two endoscopes. RESULTS: This experience enabled us to highlight a series of technical aspects essential for these techniques: 1. Pneumoperitoneum with CO(2) is safer for entry. 2. Orifice size is important to limit contamination. 3. Puncture entry and guided dilation is safer. 4. Good gastric exit location makes it easier to approach viscera to be resected. 5. Intra-abdominal haemorrhage is difficult to control. 6. Leak-free closure cannot be guaranteed with clips, but t-bars and Obesco clips may be effective. 7. Endoscopes that permit triangulation may facilitate the dissection and endoscopic suture. CONCLUSIONS: NOTES requires a multidisciplinary team comprising laparoscopic and endoscopic surgeons. Pure NOTES is complex and hybrid forms or transumbilical route could be intermediate steps.

Fetal surgery of extremity amniotic bands: an experimental model of in utero limb salvage in fetal lamb.

BACKGROUND: Extremity amniotic band (EAB) syndrome can cause an intrauterine amputation as a result of a mechanical effect with progressive strangulation. The aim of the study is to assess the use of fetal surgery of EABs with risk of amputation in the ovine fetus. METHODS: Right limbs of fifteen 60-day-gestational age fetal sheep were ligated with silk suture at the infracondylar level. Left limbs were used for paired comparison. Fetuses were randomized into 3 groups: an early-repair group (n = 5), a late-repair group (n = 5), and a nonrepaired group (n = 5). The limbs of the 2 repaired groups underwent fetal release. The limbs obtained from at-term fetuses were analyzed morphologically, functionally, and radiologically. Statistical analysis with paired test was used to compare data. RESULTS: Nonrepaired limbs showed amputation or quasi amputation; the repaired ones did not. However, those late-repaired had significantly reduced passive ankle range of motion, shorter limb length, and mild residual changes. CONCLUSIONS: Intrauterine release of potentially severe EABs prevents limb amputation and leads to morphofunctional recovery. Early release shows better results. CLINICAL RELEVANCE: : Intrauterine amputations caused by EABs in the human fetus might be avoidable by fetal surgery.