Animal Feasibility Study Research Articles

Percutaneous Alginate Hydrogel Endomyocardial Injection with a Novel Dedicated Catheter Delivery System: An Animal Feasibility Study

The objective of this preclinical study was to evaluate the feasibility and safety of transcatheter endocardial alginate hydrogel injection (TEAi) in a large animal model, utilizing the high-stiffness XDROP® alginate hydrogel in combination with the dedicated EndoWings® catheter-based system. All swine (n = 9) successfully underwent TEAi without complications. Acute results from a subset of animals (n = 5) demonstrated the ability of the catheter to access a wide range of endomyocardial areas and achieve consecutive circumferential hydrogel distribution patterns within the mid-left ventricular wall. Histological examinations at 6 months (n = 4) demonstrated that the XDROP® remained localized within the cardiac tissue. In addition, serial echocardiographic imaging showed that XDROP® had no adverse impacts on LV systolic and diastolic functions. In conclusion, this innovative combination technology has the potential to overcome the translational barriers related to alginate hydrogel delivery to the myocardium.Graphical abstract

Bipolar endo-epicardial RF ablation: Animal feasibility study

BackgroundBipolar radiofrequency ablation (B-RFA) is a method used to treat the arrhythmia substrate resistant to unipolar ablation. Few studies have addressed endo-epicardial B-RFA. ObjectiveThe aim of the study was to evaluate chronic lesions resulting from endo-epicardial B-RFA and to determine optimal settings for such procedures in an animal model. MethodsIn 7 pigs, up to 5 radiofrequency applications per animal were performed with 2 electrodes placed on both sides of the left ventricular free wall. Current was delivered for 60 seconds by a generator dedicated for B-RFA with power settings of 25, 30, 35, 40, and 50 W. ResultsAt 12 weeks after ablation, 31 lesions were assessed. Their maximal cross-sectional area ranged from 7.2 to 68 mm2 and correlated with total power delivered (r = 0.53), with temperature increment at the endocardial catheter (r = 0.65), and inversely with temperature decrement at the epicardial catheter (r = 0.54). For power values between 30 and 40 W, the lesion area did not differ significantly (P = .92). Lesion depth ranged from 1.9 to 11 mm and correlated with impedance decrement (r = 0.5). Lesions were transmural in 8 cases. Lesion depth/wall thickness ratio was on average 0.6 ± 0.3, with the smallest value for 25 W (0.5 ± 0.3) and the largest for 50 W (0.8 ± 0.3). Steam pops occurred at a power range of 30–50 W, with an incidence of 1 in 5 applications, with 1 case of fatal tamponade at 40 W. Impedance decrement, endocardial catheter temperature increment, and endocardial electrogram amplitude decrement were greater during applications with steam pops. ConclusionChronic lesions resulting from endo-epicardial B-RFA appear smaller and less often transmural compared with acute lesions described in the literature. The incidence of steam pops during endo-epicardial B-RFA is relatively high even at low powers.

Animal Feasibility Study of a Novel Spinal Cord Stimulation Multicolumn Lead (Heron Lead).

Currently available spinal cord stimulation paddle leads require a laminectomy, limiting the types of clinicians who can implant and increasing the risk of complications. Recently, WISE S.r.l. designed a prototype multicolumn lead named the Heron® lead that can be implanted percutaneously. The purpose of the study was to examine the efficiency of placing a paddle lead percutaneously. Ten sheep were assigned to either the Heron lead group (n = 7) or the control group (n = 3). The sheep were observed for 13 weeks after implantation. Neurological and clinical examinations were conducted prior to surgery and then during the follow-up period. The implantation sites were evaluated through macroscopic observations during the article explantation and the lead migration was evaluated by comparing the article positioning at the surgery, four weeks after the surgery and at the explantation day through fluoroscope images. A qualitative comparison was made between the results collected with the test article and the control article. Observations at the surgical sites indicate that test animals appeared to have less swelling around the surgical wound than control ones in the first 14 days, but no impact on wound healing was noticed. Additionally, no clear difference was observed in pain scores between the two groups, with observations tending to show that the maximum pain was occurring later in the test group with respect to the control group. General clinical observations showed no major difference between the two groups, and determined clinical abnormalities were not directly related to the procedure. Lastly, neurological deficits frequency decreased from the first to last animal operated, regardless of their test or control status. Our study concluded that the Heron lead is safe to implant, with a safety profile similar to the control article. Additionally, we conclude that the Heron lead is effective in reducing lead migration events.

Remote robotic percutaneous coronary intervention: An animal feasibility study.

The purpose of this study was to explore the feasibility and safety of robotic PCI performed using an off-siteremote-control system in an animal model. Access to primary percutaneous coronary intervention (PCI) remains a challenge in acute myocardial infarction management. The combination of telemedicine and robotic PCI allow the potential delivery of primary PCI to remote locations without the delay of transfer. This single-center prospective pilot preclinical feasibility study compared robotic PCI with remote PCI on swine across three stages (adjacent room, different floor of the same building, two different buildings). Latency up to 1,000 ms was introduced into the operating environment to simulate decreased network quality (blinded to operator). The primary outcome measures were technical success and acute safety. The secondary outcome measures included lesion wiring time, procedural time and qualitative scoring of the PCI experience by the operator. Across 52 experiments in 15 animals, technical success was 100%. No procedural complications occurred during the study. No significant difference in lesion treatment time was detected between stages (p = .11) and between time per target vessel when latency up to 1,000 ms was introduced (p = .58). Injected delay >250 ms had the greatest impact on procedure perceived lag. Longer procedure time was associated with lower procedure impact score, regardless of injected latency. Remote robotic PCI was feasible and safe in an animal model. Procedural duration was acceptable and unaffected by network latency. Future studies are needed to determine the safety and feasibility of remote PCI in humans.

Novel submucosal lifting gel for performing endoscopic mucosal resection after precutting in large gastric lesions: An animal feasibility study

Novel submucosal lifting gel for performing endoscopic mucosal resection after precutting in large gastric lesions: An animal feasibility study

Electrical conductivity-based contrast imaging for characterizing prostatic tissues: in vivo animal feasibility study

BackgroundElectrical conductivity-based magnetic resonance (MR) imaging may provide unique information on tissue condition because its contrast originates from the concentration and mobility of ions in the cellular space. We imaged the conductivity of normal canine prostate in vivo and evaluated tissue contrast in terms of both the conductivity distribution and anatomical significance.MethodsFive healthy laboratory beagles were used. After clipping the pelvis hair, we attached electrodes and placed each dog inside the bore of an MRI scanner. During MR scanning, we injected imaging currents into two mutually orthogonal directions between two pairs of electrodes. A multi spin echo pulse sequence was used to obtain the MR magnitude and magnetic flux density images. The projected current density algorithm was used to reconstruct the conductivity image.ResultsConductivity images showed unique contrast depending on the prostatic tissues. From the conductivity distribution, conductivity was highest in the center area and lower in the order of the middle and outer areas of prostatic tissues. The middle and outer areas were, respectively, 11.2 and 25.5% lower than the center area. Considering anatomical significance, conductivity was highest in the central zone and lower in the order of the transitional and peripheral zones in all prostates. The transitional and peripheral zones were, respectively, 7.5 and 17.8% lower than the central zone.ConclusionsCurrent conductivity-based MR imaging can differentiate prostatic tissues without using any contrast media or additional MR scans. The electrical conductivity images with unique contrast to tissue condition can provide a prior information on tissues in situ to be used for human imaging.

349 A Natural Orifice Transluminal Endoscopic Surgical Approach to Cruroplasty for GERD Management: A Feasibility Study in an Acute Porcine Model

INTRODUCTION: Gastroesophageal reflux disease is a common condition that often requires long term medical management or elective surgery in the form of fundoplication. Advanced endoscopic techniques can potentially be able to supply a safer alternative for patients with reflux disease. We propose a natural orifice transluminal endoscopic surgical technique that uses a self-approximating submucosal tunnel approach to the mediastinum to perform an anti-reflux procedure. CASE DESCRIPTION/METHODS: An acute porcine model was used for this acute animal feasibility study. Female Yorkshire pigs were kept on a liquid diet for forty eight hours and nothing by mouth eight hours prior to endoscopy. All animals were anesthetized and monitored. A four to five centimeter long submucosal tunnel is created in the posterior esophagus, beginning about ten centimeters above the gastroesophageal junction. From inside the tunnel, the muscles are incised to gain entry into the mediastinum. The esophagus is then followed down to the diaphragmatic hiatus and the right and left crura are located. The aorta, the vagal nerves, and other surrounding structures are identified. Using an overstitch device fitted on a double channel scope, we then suture the crura posteriorly, effecting a cruroplasty. Following the procedure, the animals were euthanized and immediate necropsy was performed to assess for any complications as well as determine the success of the cruroplasty. Esophageal pressure was assessed endoscopically in one animal. DISCUSSION: A submucosal tunnel was successfully achieved in all three animals with safe entry into the mediastinum. Mediastinal and then peri hiatal anatomy was demonstrated in each animal with excellent view of the thoracic aorta, esophagus, right and left vagus nerves, lungs, and the diaphragmatic crura. Endosuturing was successful with effective cruroplasty in all three animals without complications. Necropsy showed that sutures were in correct anatomical location without signs of procedural complication. We conclude that it is entirely possible to access the diaphragmatic hiatus and perform endoscopic cruroplasty for the potential treatment of reflux disease. A survival study aimed at developing a full-fledged anti reflux procedure is currently underway. We speculate that a trans-esophageal approach can provide an easy and safe treatment option for selected patients suffering from reflux disease. Watch the video: http://bit.ly/2JQiEaF

Validation of ultrasound as a diagnostic tool to assess vocal cord motion in an animal feasibility study.

Post-thyroidectomy dysphonia can result from recurrent laryngeal nerve (RLN) injury. Confirmation of postoperative recurrent nerve function has prompted many surgeons to advocate laryngoscopic examination. Indirect and flexible laryngoscopy permit visualization of vocal cord motion, but not all thyroid surgeons are skilled in these techniques. Indirect laryngoscopy has a significant failure rate due to gag reflexes or anatomical obstruction. Flexible fiberoptic laryngoscopy, the current gold standard, allows reliable visualization of the cords, but perioperative examination is not always feasible for lack of equipment or training. Recent studies suggest vocal fold ultrasound as an alternative to flexible laryngoscopy. It offers the advantages of being non-invasive and painless without radiation exposure or sedation. Whereas ultrasound has been compared to laryngoscopy in the clinical setting, there remains a need for correlation of laryngeal ultrasound results with known neurophysiology in the normal and injured state. An animal model was proposed that reproduces neck surgery-associated recurrent nerve injury. The model allowed simultaneous recording of laryngeal endoscopy and transcutaneous high-resolution ultrasound during stimulation of intact and injured RLNs. One RLN was injured in each of 4 rats. Rats were kept anesthetized during the fiberoptic examination and laryngeal ultrasound procedures. Following surgery and subsequent imaging the rats were given a lethal anesthetic dose. Results of both imaging modalities were compared to the presence or absence of neuromuscular action potential following stimulation of the recurrent nerve. The investigators observed a 100% correlation between endoscopic and ultrasonographic assessments. This study validated the clinical use of diagnostic ultrasound in vocal cord dysfunction in a rodent model.

Endoscopic submucosal tunnel dissection using a novel bracing basket: An animal feasibility study

The aim of this study was to evaluate the feasibility of a novel bracing basket for Endoscopic submucosal tunnel dissection (ESTD), which was developed for improved effectiveness and ease of use. This was a prospective randomized, comparative, experimental animal study carried out at a single center. The primary aim was to evaluate the efficacy of ESTD with a novel bracing basket, compared with conventional ESTD. The secondary aims were to assess the quality control of the procedures and adverse events. Twenty procedures (6 esophageal and 14 gastric) were performed in four pigs. All resections were completed as en bloc resections. The technical success rate was 100% for both techniques (bracing basket-assisted ESTD vs. conventional ESTD). The procedure times were similar, but the cutting speed was quicker with bracing basket-assisted ESTD in gastric (antrum:23.3 ± 2.2 mm2/min vs. 15.2 ± 3.2 mm2/min, body: 26.1 ± 1.3 mm2/min vs. 18.4 ± 2.0 mm2/min, p < 0.05). There was one bleeding in the bracing basket-assisted ESTD group and one perforation in the conventional ESTD group. Compared with conventional ESTD, the use of this basket has potential advantages. Comparison studies with larger gastric or colorectal lesions treated with conventional ESTD are needed.

Mo1981 Endoscopic Closure Using a Temperature-Responsive, Biodegradable and Injectable Collagen Sol for Perforation During Endoscopic Submucosal Dissection: an Animal Feasibility Study

Mo1981 Endoscopic Closure Using a Temperature-Responsive, Biodegradable and Injectable Collagen Sol for Perforation During Endoscopic Submucosal Dissection: an Animal Feasibility Study

Endoscopic colostomy with percutaneous colopexy: an animal feasibility study.

Indications for colostomy in colorectal diseases are obstruction of the large bowel, such as in cancer, diverticular disease in the acute phase, post-radiotherapy enteritis, complex perirectal fistulas, anorectal trauma and severe anal incontinence. Some critically ill patients cannot tolerate an exploratory laparotomy, and laparoscopic assisted colostomy also requires general anesthesia. To evaluate the feasibility, safety and efficacy of performing colostomy assisted by colonoscopy and percutaneous colopexy. Five pigs underwent endoscopic assisted colostomy with percutaneous colopexy. Animals were evaluated in post-operative days 1, 2, 5 and 7 for feeding acceptance and colostomy characteristics. On day 7 full colonoscopy was performed on animals followed by exploratory laparotomy. Average procedure time was 27 minutes (21-54 min). Postoperative mobility and feeding of animals were immediate after anesthesia recovery. Position of the colostomy, edges color, appearance of periostomal area, as well as its function was satisfactory in four animals. Retraction of colostomy was present in one pig. The colonoscopy and laparotomy control on the seventh day were considered as normal. A bladder perforation that was successfully repaired through the colostomy incision occurred in one pig. The main limitation of this study is its experimental nature. Endoscopic assisted colostomy with percutaneous colopexy proves to be a safe and effective method with low morbidity for performing colostomy in experimental animals, with possible clinical application in humans.

Bio-sheet graft therapy for artificial gastric ulcer after endoscopic submucosal dissection: an animal feasibility study

Various bio-sheet grafts have been attempted either to accelerate healing of artificial ulcers or to prevent adverse events after endoscopic submucosal dissection (ESD), but neither prospective nor mechanistic studies were available. To evaluate the substantial effect of a bio-sheet graft on artificial ulcer healing and its feasibility as an endoscopic treatment modality. Preclinical, invivo animal experiment and proof-of-concept study. Animal laboratory. Three mini-pigs, Sus scrofa, mean age 14 months. Multiple ulcers sized 2.5 cm in diameter were generated by ESD in 3 mini-pigs and were assigned randomly into the following 3 groups; control group, bio-sheet group, or combination (bio-sheet plus drug) group. Bio-sheet grafts or bio-sheet plus drug combinations were applied on the artificial ulcers immediately after the ESD. Feasibility and efficacy of endoscopic bio-sheet graft therapy for the management of artificial ulcers and the evaluation of healing conditions based on histology changes in the remaining gastric bed tissues harvested from the stomachs. Thirty-three ESD specimens were obtained. On an image analysis of the ratio of healed area in the remaining gastric bed tissue compared with the matched dissected gastric mucosa, the control group showed the most significant improvement in healing activity among the 3 groups (P< .05), whereas the severity of inflammation in the remaining ulcer tissue was significantly attenuated in bio-sheet and combination groups (P< .05). Animal model. Although the bio-sheet grafts provided physical protection from gastric acid attack as reflected in the attenuated inflammation on the ulcer beds, unexpected delayed ulcer healing was noted in the bio-sheet graft group because of its physical hindrance of the healing process.

La kératopigmentation annulaire (ou PresbyRing®) dans la prise en charge de la presbytie : étude expérimentale de faisabilité post-mortem chez l’animal

Annular keratopigmentation (PresbyRing(®)) is a new technique which creates an intrastromal ring centered on the visual axis, using a femtosecond laser, into which a black or a colored pigment is then injected. The internal diameter of the ring is dimensioned so as to create a pinhole and improve the near and intermediate vision of the non-dominant eye while only slightly altering the distance vision of that eye. We used five pig eyes for our postmortem feasibility study; all five were treated with the Intra Corneal Ring program (ICR(®)) of the Visumax(®) laser. The dye used (Biochromaderm(®)) has EU approval. Spectral domain OCT examinations demonstrate complete opacity of the dye. Histological analysis with hematoxylin and eosin stain highlights a continuous pigmented layer located along the incision, which does not diffuse in the adjacent stroma. The possibility of rinsing the dye must be confirmed by future in-vivo animal studies. To our knowledge, this study represents the first experimental attempt to combine two ideas which did not appear to have anything in common: the creation of an intracorneal pinhole to treat presbyopia, and corneal tattooing. The first postmortem feasibility study in animals for annular keratopigmentation (PresbyRing(®)) gave encouraging results. It must be confirmed by in vivo animal studies, and ultimately in humans.

Animal feasibility study of an innovated splash‐needle for endoscopic submucosal dissection in the upper gastrointestinal tract

The high frequency of complications accompanying endoscopic submucosal dissection (ESD) and its complex processes suggest that the process requires improvement. The objective of the present study was to investigate the feasibility of an innovated splash-needle for ESD. An animal feasibility study with a living pig was conducted. Six resections per portion (esophagus and upper, middle, and lower thirds of the stomach) in a total of 24 resections were carried out by using an original splash-needle or an innovated splash-needle. Major innovations were a thicker part in the middle of the knife and a metal plate on the tip of the sheath to obtain more coagulation ability. Injection solution in the submucosal layer was also changed due to possible influence on the outcomes. Main outcome measurements were entire procedure time, cutting speed, and frequency of bleeding during ESD. All the 24 resections were completed without complications. Among the obtained data, only mean cutting speeds were significantly influenced by location of the simulated lesion, which revealed that ESD at the upper third was significantly quicker than that at the lower third (P = 0.01), and ESD at the esophagus was significantly slower than that at the three parts of the stomach (P < 0.01). There was no significant difference between the different knives in each variable. The innovated splash-needle will be feasible for human use, although the safety and advantages in clinical settings must be elucidated by proper comparative studies with existing knives in humans.

Transapical implantation of a self-expanding aortic valve bioprosthesis — animal feasibility study☆

Severe peripheral arterial disease may pose a limitation to the applicability of trans-arterial aortic valve implantation in patients who are otherwise candidates. For this reason, transapical aortic valve implantation has been proposed as a possible alternative. To evaluate the acute safety and performance of a specially designed delivery system, the CoreValve Tranzap delivery catheter, for the transapical implantation of a self-expandable aortic valve prosthesis in a porcine animal model. Thirteen pigs were implanted with a self-expandable aortic valve bioprosthesis using a 21F catheter delivery system through a transapical approach. The delivery system was evaluated for: (1) the ability to access the implantation site; (2) the ability to precisely position the delivery catheter; (3) control of the delivery of the prosthesis; (4) safe retrieval of the delivery catheter; and (5) the ability to close the apical access site of the heart. Successful implantation was achieved in 100% of the cases. The following points were achieved in all animals: (1) passage of the delivery catheter through an incision in the left ventricular apex; (2) positioning of the delivery catheter on the implantation site; (3) controlled deployment of the aortic valve prosthesis; (4) the safe retrieval of the delivery catheter system; and (5) the adequate closure of the apex of the heart. This study demonstrates the acute safety and feasibility of the CoreValve Tranzap delivery system for the transapical implantation of the CoreValve self-expanding aortic valve bioprosthesis in a porcine animal model.

Invited Commentary

The article by Meng and coworkers [1] presents the results of a long-term animal feasibility study using a newly designed, self-expanding nitinol stent supporting a bovine jugular vein valve for transventricular pulmonary valve replacement. In this experiment, 6 sheep received a valved stent during a beating heart procedure. The implantation was successful in all animals, and the valve performed well in all but in one in which an increased transvalvular gradient was measured after 2 months. In another, mild regurgitation was present after 2 months.

Transcolonic endoscopic cholecystectomy: a NOTES survival study in a porcine model (with video)

Transgastric cholecystectomy is a natural orifice transluminal endoscopic surgery (NOTES) procedure that has been reported in 2 nonsurvival studies. Both studies detail substantial technical limitations, with only a 33% success rate when limited to 1 gastric incision site, despite the use of a multichannel locking endoscope. The aim of this study was to evaluate the feasibility and technical limitations of transcolonic cholecystectomy in a survival model. Animal feasibility study. Five pigs, under general anesthesia, were prepared with tap-water enemas, a peranal antibiotic lavage, and a Betadine rinse. A dual-channel endoscope was advanced into the peritoneum through an anterior, transcolonic incision 15 to 20 cm from the anus. After cystic duct and artery ligation, dissection of the gallbladder was achieved by using grasping and cutting instruments. After removing the gallbladder, the colonic incision was closed by using Endoloops and/or endoclips. The animals lived for 2 weeks after the procedure, then they were euthanized, and a necropsy was performed. All 5 gallbladders were successfully resected. Four of the 5 animals flourished in the postoperative period, with appropriate weight gain. In 1 animal, complete closure of the colonic incision was not possible, and it was euthanized at 48 hours for suspected peritonitis. This study reports the first transcolonic organ resection and demonstrates the first successful NOTES cholecystectomy in a survival model. The transcolonic approach provided improved endoscope stability and biliary exposure compared with the transgastric route, and complete incision closure appeared critical for procedural success.

Invited commentary

The article by Attmann and coworkers [1] presents the results of a chronic animal feasibility study of using a self-expanding nitinol stent supporting a bovine jugular vein valve for percutaneous pulmonary valve replacement, and represents continuing work previously reported by the same group [2]. In this experiment, 9 sheep received the nitinol stented bovine valve percutaneously with 2 animals experiencing lethal bleeding complications attributed to the procedure and 1 animal succumbing to endocarditis at 2.5 months.

Successful Performance of Cox-Maze Procedure on Beating Heart Using Bipolar Radiofrequency Ablation: A Feasibility Study in Animals

Background The Cox-Maze procedure is the gold standard for the surgical treatment of atrial fibrillation with proven long-term efficacy. However, its application has been limited by its complexity and significant morbidity. The purpose of this study was to test the feasibility and safety of performing the Cox-Maze procedure using bipolar radiofrequency ablation on the beating heart without cardiopulmonary bypass. Methods After median sternotomy, 6 Hanford mini-pigs underwent a modified Cox-Maze procedure using bipolar radiofrequency energy. The animals survived for 30 days. Atrial function, coronary artery, pulmonary vein anatomy, and valve function were assessed by magnetic resonance imaging. At reoperation, pacing documented electrical isolation of the pulmonary veins. Induction of atrial fibrillation was attempted by burst pacing with cholinergic stimulation. Histologic assessment was performed after sacrifice. Results There were no perioperative mortalities or neurologic events. At 30 days, atrial fibrillation was unable to be induced, and pulmonary vein isolation was confirmed by pacing. Magnetic resonance imaging assessment revealed no coronary artery or pulmonary vein stenoses. Although atrial ejection fraction decreased slightly from 0.344 ± 0.0114 to 0.300 ± 0.055 ( p = 0.18), atrial contractility was preserved in every animal. Histologic assessment showed all lesions to be transmural, and there were no significant stenoses of the coronary vessels or injuries to the valves. Conclusions Virtually all of the lesions of the Cox-Maze procedure can be performed without cardiopulmonary bypass using bipolar radiofrequency energy. There were no late stenoses of the pulmonary veins. Clinical trials of this new technology on the beating heart are warranted.

Incorporation of 180 2 into brain serotonin [formula omitted][formula omitted] as a procedure for estimating turnover: A feasibility study in animals

Serotonin (5HT) containing 180 instead of 160 was found in brain after exposing rats to an atmosphere of 180 2. The 180 incorporation appeared linear with time and 22% of the 5HT in striatum contained 180 after one hour of exposure. 180 entered 5HT by enzymatic reaction rather than by isotope exchange as treatment with p-chlorophenylalanine, to block tryptophan hydroxylase, prevented incorporation, while more 180-5HT than normal was found in brain after treatment with pargyline, to block monoamine oxidase. Our studies suggest that the incorporation of 180 2 into brain 5HT might be a feasible approach for evaluating 5HT turnover in animals and with some modification might be applied in man.