Power-Controlled, Irrigated Radio-Frequency Ablation of Gastric Tissue: A Biophysical Analysis of Lesion Formation.

BACKGROUND: Radio-frequency ablation of gastric tissue is in its infancy compared to its extensive history and use in the cardiac field. AIMS: We employed power-controlled, irrigated radio-frequency ablation to create lesions on the serosal surface of the stomach to examine the impact of ablation power, irrigation, temperature, and impedance on lesion formation and tissue damage. METHODS: A total of 160 lesions were created in vivo in female weaner pigs (n = 5) using a combination of four power levels (10, 15, 20, 30 W) at two irrigation rates (2, 5 mL min-1) and with one temperature-controlled (65 °C) reference setting previously validated for electrophysiological intervention in the stomach. RESULTS: Power and irrigation rate combinations above 15 W resulted in lesions with significantly higher surface area and depth than the temperature-controlled setting. Irrigation resulted in significantly lower temperature (p < 0.001) and impedance (p < 0.001) compared to the temperature-controlled setting. No instances of perforation or tissue pop were recorded for any ablation sequence. CONCLUSION: Power-controlled, irrigated radio-frequency ablation of gastric tissue is effective in creating larger and deeper lesions at reduced temperatures than previously investigated temperature-controlled radio-frequency ablation, highlighting a substantial improvement. These data define the biophysical impact of ablation parameters in gastric tissue, and they will guide future translation toward clinical application and in silico gastric ablation modeling. Combination of ablation settings (10-30 W power, 2-5 mL min-1 irrigation) were used to create serosal spot lesions. Histological analysis of lesions quantified localized tissue damage.

Anaesthesia by intravenous propofol reduces the incidence of intra-operative gastric electrical slow-wave dysrhythmias compared to isoflurane.

Gastric motility is coordinated by bioelectrical slow-wave activity, and abnormal electrical dysrhythmias have been associated with nausea and vomiting. Studies have often been conducted under general anaesthesia, while the impact of general anaesthesia on slow-wave activity has not been studied. Clinical studies have shown that propofol anaesthesia reduces postoperative nausea and vomiting (PONV) compared with isoflurane, while the underlying mechanisms remain unclear. In this study, we investigated the effects of two anaesthetic drugs, intravenous (IV) propofol and volatile isoflurane, on slow-wave activity. In vivo experiments were performed in female weaner pigs (n = 24). Zolazepam and tiletamine were used to induce general anaesthesia, which was maintained using either IV propofol (n = 12) or isoflurane (n = 12). High-resolution electrical mapping of slow-wave activity was performed. Slow-wave dysrhythmias occurred less often in the propofol group, both in the duration of the recorded period that was dysrhythmic (propofol 14 ± 26%, isoflurane 43 ± 39%, P = 0.043 (Mann-Whitney U test)), and in a case-by-case basis (propofol 3/12, isoflurane 8/12, P = 0.015 (Chi-squared test)). Slow-wave amplitude was similar, while velocity and frequency were higher in the propofol group than the isoflurane group (P < 0.001 (Student's t-test)). This study presents a potential physiological biomarker linked to recent observations of reduced PONV with IV propofol. The results suggest that propofol is a more suitable anaesthetic for studying slow-wave patterns in vivo.

Localized bioelectrical conduction block from radiofrequency gastric ablation persists after healing: safety and feasibility in a recovery model.

Gastric ablation has demonstrated potential to induce conduction blocks and correct abnormal electrical activity (i.e., ectopic slow-wave propagation) in acute, intraoperative in vivo studies. This study aimed to evaluate the safety and feasibility of gastric ablation to modulate slow-wave conduction after 2 wk of healing. Chronic in vivo experiments were performed in weaner pigs (n = 6). Animals were randomly divided into two groups: sham-ablation (n = 3, control group; no power delivery, room temperature, 5 s/point) and radiofrequency (RF) ablation (n = 3; temperature-control mode, 65°C, 5 s/point). In the initial surgery, high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was performed to define the baseline slow-wave activation profile. Ablation (sham/RF) was then performed in the mid-corpus, in a line around the circumferential axis of the stomach, followed by acute postablation mapping. All animals recovered from the procedure, with no sign of perforation or other complications. Two weeks later, intraoperative high-resolution mapping was repeated. High-resolution mapping showed that ablation successfully induced sustained conduction blocks in all cases in the RF-ablation group at both the acute and 2 wk time points, whereas all sham-controls had no conduction block. Histological and immunohistochemical evaluation showed that after 2 wk of healing, the lesions were in the inflammation and early proliferation phase, and interstitial cells of Cajal (ICC) were depleted and/or deformed within the ablation lesions. This safety and feasibility study demonstrates that gastric ablation can safely and effectively induce a sustained localized conduction block in the stomach without disrupting the surrounding slow-wave conduction capability.NEW & NOTEWORTHY Ablation has recently emerged as a tool for modulating gastric electrical activation and may hold interventional potential for disorders of gastric function. However, previous studies have been limited to the acute intraoperative setting. This study now presents the safety of gastric ablation after postsurgical recovery and healing. Localized electrical conduction blocks created by ablation remained after 2 wk of healing, and no perforation or other complications were observed over the postsurgical period.

The Effect of Power-Control and Irrigation Settings on Lesion Size during Radio-Frequency Ablation of Gastric Tissue.

Gastric ablation has recently emerged as a promising potential therapy for correcting bioelectrical dysrhythmias that underpin many gastrointestinal motility disorders. Despite similarities to well-developed cardiac radiofrequency (RF) ablation, gastric RF ablation is in its infancy and has thus far been limited to temperature-controlled, non-irrigated settings. The potential benefits of power-controlled and irrigated RF ablation have not been investigated in gastric tissue. In this study, RF ablation was performed in vivo in pigs ( n=5) using a range of power-control (10-30 W, 10s per point) and irrigation (2-5 ml/min) settings and compared to known temperature-controlled (65°C), non-irrigated settings. Excised tissue was stained with H&E. Lesion surface area was calculated and tissue damage was quantitatively ranked by visual assessment. The results demonstrated that irrigation allowed greater energy delivery to tissue with reduced interface temperatures compared to non-irrigated settings. Power settings above 10 W created lesions that extended through the full-thickness of the muscle layer, which suggests the parameter range that can now be used to correct gastric dysrhythmias. Clinical Relevance- This work presents the results of power-controlled, irrigated RF ablation settings applied to the in vivo porcine stomach. The relationships of both lesion area and depth to ablation dose provides an improved insight into which energy doses could provide a safe and effective therapeutic response.

Targeted ablation of gastric pacemaker sites to modulate patterns of bioelectrical slow wave activation and propagation in an anesthetized pig model.

Gastric motility is coordinated by underlying bioelectrical slow waves. Gastric dysrhythmias occur in gastrointestinal (GI) motility disorders, but there are no validated methods for eliminating dysrhythmias. We hypothesized that targeted ablation could eliminate pacemaker sites in the stomach, including dysrhythmic ectopic pacemaker sites. In vivo high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was applied to localize normal and ectopic gastric pacemaker sites in 13 anesthetized pigs. Radiofrequency ablation was performed in a square formation surrounding the pacemaker site. Postablation high-resolution mapping revealed that ablation successfully induced localized conduction blocks after 18 min (SD 5). Normal gastric pacemaker sites were eliminated by ablation (n = 6), resulting in the emergence of a new pacemaker site immediately distal to the original site in all cases. Ectopic pacemaker sites were similarly eliminated by ablation in all cases (n = 7), and the surrounding mapped area was then entrained by normal antegrade activity in five of those cases. Histological analysis showed that ablation lesions extended through the entire depth of the muscle layer. Immunohistochemical staining confirmed localized interruption of the interstitial cell of Cajal (ICC) network through the ablation lesions. This study demonstrates that targeted gastric ablation can effectively modulate gastric electrical activation, including eliminating ectopic sites of slow wave activation underlying gastric dysrhythmias, without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.NEW & NOTEWORTHY This study presents gastric ablation as a novel tool for modulating gastric bioelectrical activation, including eliminating the normal gastric pacemaker site as well as abnormal ectopic pacemaker sites underlying gastric dysrhythmias. Targeted application of radiofrequency ablation was able to eliminate these pacemaker sites without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.

A computational model of radiofrequency ablation in the stomach, an emerging therapy for gastric dysrhythmias.

Gastric ablation has recently emerged as a promising potential therapy for bioelectrical dysrhythmias that underpin many gastrointestinal disorders. Despite similarities to well-developed cardiac ablation, gastric ablation is in early development and has thus far been limited to temperature-controlled, non-irrigated settings. A computational model of gastric ablation is needed to enable in silico testing and optimization of ablation parameters and techniques. In this study, we developed a computational model of radio-frequency (RF) gastric ablation. Model parameters and boundary conditions were established based on the current in vivo experimental application of serosal gastric ablation with a non-irrigated RF catheter. The Pennes bioheat transfer equation was used to model the thermal component of RF ablation, and Laplace's equation was used to model the Joule heating component. Tissue, blood, and catheter parameters were obtained from literature. The performance of the model was compared to previously established experimental values of temperature measured from various distances from the catheter tip. The model produced temperature estimations that were within 6% of the maximum experimental temperature at 2.5 mm from the catheter, and within 13% of the maximum temperature change at 4.7 mm. This model now provides a computational basis through which to conduct in silico testing of gastric ablation, and can be usefully applied to optimize gastric ablation parameters. In future, the model can be expanded to include irrigation of the catheter tip and power-controlled RF settings.Clinical Relevance- This work presents a computational model of gastric ablation that can now guide the in silico development of effective ablation parameters and therapeutic strategies, expanding the breadth of this promising therapy.

Localized gastric distension disrupts slow-wave entrainment leading to temporary ectopic propagation: a high-resolution electrical mapping study.

Gastric distension is known to affect normal slow-wave activity and gastric function, but links between slow-wave dysrhythmias and stomach function are poorly understood. Low-resolution mapping is unable to capture complex spatial properties of gastric dysrhythmias, necessitating the use of high-resolution mapping techniques. Characterizing the nature of these dysrhythmias has implications in the understanding of postprandial function and the development of new mapping devices. In this two-phase study, we developed and implemented a protocol for measuring electrophysiological responses to gastric distension in porcine experiments. In vivo, serosal high-resolution electrical mapping (256 electrodes; 36 cm2) was performed in anaesthetized pigs (n = 11), and slow-wave pattern, velocity, frequency, and amplitude were quantified before, during, and after intragastric distension. Phase I experiments (n = 6) focused on developing and refining the distension mapping methods using a surgically inserted intragastric balloon, with a variety of balloon types and distension protocols. Phase II experiments (n = 5) used barostat-controlled 500-mL isovolumetric distensions of an endoscopically introduced intragastric balloon. Dysrhythmias were consistently induced in all five gastric distensions, using refined distension protocols. Dysrhythmias appeared 23 s (SD = 5 s) after the distension and lasted 129 s (SD = 72 s), which consisted of ectopic propagation originating from the greater curvature in the region of distension. In summary, our results suggest that distension disrupts gastric entrainment, inducing temporary ectopic slow-wave propagation. These results may influence the understanding of the postprandial stomach and electrophysiological effects of gastric interventions.NEW & NOTEWORTHY This study presents the discovery of temporary dysrhythmic ectopic pacemakers in the distal stomach caused by localized gastric distension. Distension-induced dysrhythmias are an interesting physiological phenomenon that can inform the design of new interventional and electrophysiological protocols for both research and the clinic. The observation of distension-induced dysrhythmias also contributes to our understanding of stretch-sensitivity in the gut and may play an important role in normal and abnormal postprandial physiology.

Design and Validation of a Surface-Contact Electrode for Gastric Pacing and Concurrent Slow-Wave Mapping.

OBJECTIVE: Gastric contractions are, in part, coordinated by slow-waves. Functional motility disorders are correlated with abnormal slow-wave patterns. Gastric pacing has been attempted in a limited number of studies to correct gastric dysmotility. Integrated electrode arrays capable of pacing and recording slow-wave responses are required. METHODS: New flexible surface-contact pacing electrodes (SPE) that can be placed atraumatically to pace and simultaneously map the slow-wave activity in the surrounding area were developed. SPE were applied in pigs in-vivo for gastric pacing along with concurrent high-resolution slow wave mapping as validation. Histology was conducted to assess for tissue damage around the pacing site. SPE were compared against temporary cardiac pacing electrodes (CPE), and hook-shaped pacing electrodes (HPE), for entrainment rate, entrainment threshold, contact quality, and slow-wave propagation patterns. RESULTS: Pacing with SPE (amplitude: 2 mA, pulse width: 100 ms) consistently achieved pacemaker initiation. Histological analysis illustrated no significant tissue damage. SPE resulted in a higher rate of entrainment (64%) than CPE (37%) and HPE (24%), with lower entrainment threshold (25% of CPE and 16% of HPE). High resolution mapping showed that there was no significant difference between the initiated slow-wave propagation speed for SPE and CPE (6.8 ± 0.1 vs 6.8 ± 0.2 mm/s, P>0.05). However, SPE had higher loss of tissue lead contact quality than CPE (42 ± 16 vs 13 ± 10% over 20 min). CONCLUSION: Pacing with SPE induced a slow-wave pacemaker site without tissue damage. SIGNIFICANCE: SPE offered an atraumatic pacing electrode with a significant reduction of power consumption and placement time compared to impaled electrodes.

Gastric ablation as a novel technique for modulating electrical conduction in the in vivo stomach.

Gastric motility is coordinated by underlying bioelectrical "slow wave" activity. Slow wave dysrhythmias are associated with motility disorders, including gastroparesis, offering an underexplored potential therapeutic target. Although ablation is widely used to treat cardiac arrhythmias, this approach has not yet been trialed for gastric electrical abnormalities. We hypothesized that ablation can create localized conduction blocks and modulate slow wave activation. Radiofrequency ablation was performed on the porcine serosa in vivo, encompassing a range of parameters (55-85°C, adjacent points forming a line, 5-10 s/point). High-resolution electrical mapping (16 × 16 electrodes; 6 × 6 cm) was applied to define baseline and acute postablation activation patterns. Tissue damage was evaluated by hematoxylin and eosin and c-Kit stains. Results demonstrated that RF ablation successfully induced complete conduction block and a full thickness lesion in the muscle layer at energy doses of 65-75°C for 5-10 s/point. Gastric ablation may hold therapeutic potential for gastric electrical abnormalities in the future.NEW & NOTEWORTHY This study presents gastric ablation as a new method for modulating slow wave activation and propagation in vivo, by creating localized electrical conduction blocks in the stomach, validated by high-resolution electrical mapping and histological tissue analysis. The results define the effective energy dose range for creating conduction blocks, while maintaining the mucosal and submucosal integrity, and demonstrate the electrophysiological effects of ablation. In future, gastric ablation can now be translated toward disrupting dysrhythmic slow wave activation.

Fabrication and evaluation of chitosan/gelatin/PVA hydrogel incorporating honey for wound healing applications: An in vitro, in vivo study.

In this study, physically cross-linked hydrogels were developed by freezing-thawing method while different concentrations of honey were included into the hydrogels for accelerated wound healing. The hydrogel was composed of chitosan, polyvinyl alcohol (PVA), and gelatin with the ratio of 2:1:1 (v/v), respectively. Further, the effect of honey concentrations on antibacterial properties, and cell behavior was investigated. In vivo studies, including wound healing mechanism using rat model and histological analysis of section tissue samples were performed. The results illustrated that the incorporation of honey in hydrogels increased the ultimate strain of hydrogels approximately two times, while reduced the ultimate tensile strength and elastic modulus of hydrogels. Moreover, the antibacterial activities of samples were increased by increasing the concentration of honey. Regarding MTT assay, as the concentration of honey increased, the cell viability of hydrogels was enhanced until an optimal amount of honey. Further, the integration of honey into the hydrogel matrix results in the maintenance of a well-structured layer of epidermis containing mature collagen and accelerates the rate of wound healing. The 3D Chitosan/PVA/Gelatin hydrogel containing honey with appropriate mechanical, antibacterial activity, and biocompatibility could be a promising approach for wound healing.

A V-Net Based Deep Learning Model for Segmentation and Classification of Histological Images of Gastric Ablation.

Gastric motility disorders are associated with bioelectrical abnormalities in the stomach. Recently, gastric ablation has emerged as a potential therapy to correct gastric dysrhythmias. However, the tissue-level effects of gastric ablation have not yet been evaluated. In this study, radiofrequency ablation was performed in vivo in pigs (n=7) at temperature-control mode (55-80°C, 5-10 s per point). The tissue was excised from the ablation site and routine H&E staining protocol was performed. In order to assess tissue damage, we developed an automated technique using a fully convolutional neural network to segment healthy tissue and ablated lesion sites within the muscle and mucosa layers of the stomach. The tissue segmentation achieved an overall Dice score accuracy of 96.18 ± 1.0 %, and Jacquard score of 92.77 ± 1.9 %, after 5-fold cross validation. The ablation lesion was detected with an overall Dice score of 94.16 ± 0.2 %. This method can be used in combination with high-resolution electrical mapping to define the optimal ablation dose for gastric ablation.Clinical Relevance-This work presents an automated method to quantify the ablation lesion in the stomach, which can be applied to determine optimal energy doses for gastric ablation, to enable clinical translation of this promising emerging therapy.

Trace Mapping: A New Visualization Technique for Analyzing Gastrointestinal High-Resolution Electrical Mapping Data.

Visualization techniques are an important tool for understanding high-resolution mapping data in gastric electrophysiology. Isochronal maps and animations provide excellent depictions of spatial propagation patterns, but fail to capture temporal features of electrical activity. In this work, 'trace mapping' was developed and validated as a method for visualizing high-resolution mapping data. A combination of dots and lines represent events and temporal groups, respectively, creating patterns that can be quickly and efficiently interpreted. This work outlines trace mapping methods and introduces a shape-based pattern recognition method for efficient interpretation of trace maps. These methods provide a new perspective for understanding and evaluating gastric electrophysiology.Clinical Relevance-This work provides new visualization methods that can help clinicians interpret and diagnose gastric electrical abnormalities in patients with functional gastrointestinal disorders.

Transmural Temperature Monitoring to Quantify Thermal Conduction And Lesion Formation During Gastric Ablation, an Emerging Therapy for Gastric Dysrhythmias.

Gastric ablation is emerging as a potential therapy for electrical dysrhythmias associated with gastric disorders. Thermal conduction properties of gastric tissue during ablation have not yet been defined, but are necessary for optimizing the technique and translating ablation to clinical therapy. We developed custom needle-based transmural temperature probes to quantify the temperature of gastric tissue during ablation. These probes were applied in vivo in pigs (n=5), during gastric ablation (70 °C, 10 s duration), at distances of 2.5 - 20 mm from the ablation catheter tip. Thermal response of the tissue was non-linear; the maximum temperature increase from baseline (33.3 ± 1.0 °C) was observed at the closest temperature probe to the catheter tip (2.5 mm, 14.9 °C), and temperature change decreased with distance from the catheter tip. Probes positioned between 5 -20 mm from the catheter tip recorded temperature increases of less than 5.6 °C. This study provides methods for monitoring temperature during in vivo ablation, and demonstrates that functional temperature increases from ablation were restricted to within approximately 5 mm of the catheter. These methods can now be applied to optimize effective ablation parameters, and to inform models of gastric ablation.

A comparative study of wound dressings loaded with silver sulfadiazine and silver nanoparticles: In vitro and in vivo evaluation.

In the current study, two series of antimicrobial dressings conjugated with silver sulfadiazine (SSD) and silver nanoparticles (AgNPs) were developed and evaluated for chronic wound healing. Highly porous polycaprolactone (PCL)/polyvinyl alcohol (PVA) nanofibers were loaded with different concentrations of SSD or AgNPs and compared comprehensively in vitro and in vivo. SSD and AgNPs indicated a strong and equal antimicrobial activity against S. aureus. However, SSD had more toxicity against fibroblast cells over one week in vitro culture. An in vivo model of wound healing on male Wistar rats was developed with a full thickness wound. All the wound dressings indicated enough flexibility and hydrophilicity, which resulted an adequate adhesion into the wound closure. After 30 days, the control group without any treatment indicated 31% wound closure while the group treated with PCL/PVA (without antimicrobial components) indicated 44% wound closure. Presence of antimicrobial components in the PCL/PVA nanofibers resulted into a lower inflammation response leading to a faster proliferation and maturation phases. In agreement with the higher biocompatibility of AgNPs than SSD, a faster angiogenesis, epithelialization and subsequently, remodeling were observed for the wound dressings loaded with AgNPs. The group treated with the highest concentration of AgNPs showed the fastest healing process leading to a final epithelialization with 96% wound closure after 30 days. This study indicated that AgNPs have higher biocompatibility and regulate wound healing process more efficiently compared to SSD. PCL/PVA nanofibers conjugated with AgNPs are promising wound dressings for full-thickness wounds.

Feasibility of High-Resolution Electrical Mapping for Characterizing Conduction Blocks Created by Gastric Ablation.

The interstitial cells of Cajal (ICC) initiate, coordinate and propagate bioelectrical slow wave activity that drives gastric motility. In the healthy human stomach, slow wave activity is highly organized. Gastric motility disorders are associated with dysrhythmias. While ablation is widely used to treat cardiac dysrhythmias, this approach has yet to be trialed in the stomach. In this study, radiofrequency (RF) ablation was applied in pig stomachs in vivo to create targeted electrical conduction blocks. Ablations were performed at temperature control mode (55-70°C), and resultant conduction blocks were identified and verified using high-resolution electrical mapping. Termination of slow wave propagation at ablation sites was confirmed by a decrease in extracellular slow wave amplitude from 1.7 ± 0.2 mV to an undetectable amplitude, as well as spatiotemporal pattern analysis of conduction blocks. The use of high-resolution electrical mapping can now be employed to investigate ablation as a potential therapy for gastric dysrhythmias in motility disorders.

Methods for Visualization of Gastric Endoscopic Mapping Data From Three-Dimensional, Non-Uniform Electrode Arrays.

Methods were developed for visualizing three-dimensional endoscopic slow wave mapping data. Simulations representative of normal and abnormal slow wave propagation patterns were generated, allowing qualitative and quantitative evaluation of gridded and spherical interpolation algorithms. Three-dimensional isochronal maps provided a visual representation of slow wave propagation patterns, while mean absolute errors provided a quantitative metric for interpolation performance. Spherical thin plate spline interpolation provided an improvement over current gridded interpolation methods, with a 1.5 to 3.0 fold reduction of mean absolute errors (0.25-0.30 s to 0.08-0.15 s) over three classes of propagation patterns. Different electrode arrangements and densities were tested. A 128-electrode Fibonacci spiral arrangement was proposed as an efficient layout for capturing slow wave dynamics. These methods provide a new visualization technique suitable for endoscopic mapping, and provide a framework for testing and evaluating new interpolation techniques and device designs.

Accelerated full-thickness wound healing via sustained bFGF delivery based on a PVA/chitosan/gelatin hydrogel incorporating PCL microspheres.

Herein, a hybrid hydrogel/microsphere system is introduced for accelerated wound healing by sustained release of basic fibroblast growth factor (bFGF). The hydrogel is composed of a mixture of PVA, gelatin and chitosan. The double-emulsion-solvent-evaporation method was utilized to obtain microspheres composed of PCL, as the organic phase, and PVA, as the aqueous phase. Subsequently, various in-vitro and in-vivo assays were performed to characterize the system. BSA was used to optimize the release mechanism, and encapsulation efficiency in microspheres, where a combination of 3% (w/v) PCL and 1% (w/v) PVA was found to be the optimum microsphere sample. Incorporation of microspheres within the hydrogel substrate also led to a zero-order release kinetics. Results from SEM images, also represented an average porosity of 54%, and average mean pore size of 35 ±â€¯7 µm for the hydrogel system, and the diameter of 5 ±â€¯2 µm for the microspheres. Moreover, in vivo study including wound healing process, and histological analysis regarding re-epithelization, angiogenesis, inflammation, fibroblast genesis and collagen formation were performed using Hematoxyline-Eosin (H&E) staining, Periodic Acid-Schiff (PAS) staining and Masson's Trichrome staining. In-vivo results represented that sustained delivery of bFGF promoted by biocompatibility of PVA/chitosan/gelatin hydrogel, significantly contribute to accelerated wound healing.