Electromechanical coupling and anatomy of the in vivo gastroduodenal junction.

Few biomarkers support the diagnosis and treatment of disorders of gut-brain interaction (DGBI), although gastroduodenal junction (GDJ) electromechanical coupling is a target for novel interventions. Rhythmic "slow waves," generated by interstitial cells of Cajal (ICC), and myogenic "spikes" are bioelectrical mechanisms underpinning motility. In this study, simultaneous in vivo high-resolution electrophysiological and impedance planimetry measurements were paired with immunohistochemistry to elucidate GDJ electromechanical coupling. Following ethical approval, the GDJ of anaesthetized pigs (n = 12) was exposed. Anatomically specific, high-resolution electrode arrays (256 electrodes) were applied to the serosa. EndoFLIP catheters (16 electrodes; Medtronic, MN) were positioned luminally to estimate diameter. Postmortem tissue samples were stained with Masson's trichrome and Ano1 to quantify musculature and ICC. Electrical mapping captured slow waves (n = 512) and spikes (n = 1,071). Contractions paralleled electrical patterns. Localized slow waves and spikes preceded rhythmic contractions of the antrum and nonrhythmic contractions of the duodenum. Slow-wave and spike amplitudes were correlated in the antrum (r = 0.74, P < 0.001) and duodenum (r = 0.42, P < 0.001). Slow-wave and contractile amplitudes were correlated in the antrum (r = 0.48, P < 0.001) and duodenum (r = 0.35, P < 0.001). Distinct longitudinal and circular muscle layers of the antrum and duodenum had a total thickness of (2.8 ± 0.9) mm and (0.4 ± 0.1) mm, respectively. At the pylorus, muscle layers merged and thickened to (3.5 ± 1.6) mm. Pyloric myenteric ICC covered less area (1.5 ± 1.1%) compared with the antrum (4.2 ± 3.0%) and duodenum (5.3 ± 2.8%). Further characterization of electromechanical coupling and ICC biopsies may generate DGBI biomarkers.NEW & NOTEWORTHY This study applies electrical mapping, impedance planimetry, and histological techniques to the gastroduodenal junction to elucidate electromechanical coupling in vivo. Contractions of the terminal antrum and pyloric sphincter were associated with gastric slow waves. In the duodenum, bursts of spike activity triggered oscillating contractions. The relative sparsity of myenteric interstitial cells of Cajal in the pylorus, compared with the adjacent antrum and duodenum, is hypothesized to prevent coupling between antral and duodenal slow waves.

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.