Gastric motility is coordinated by underlying bioelectrical slow waves. Gastric dysrhythmias occur in 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 anaesthetised pigs. Radiofrequency ablation was performed in a square formation surrounding the pacemaker site. Post-ablation 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 5 of those cases. Histological analysis showed that ablation lesions extended through the entire depth of the muscle layer. Immunohistochemical staining confirmed localised 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.
Gastric motility is coordinated by underlying bioelectrical 'slow wave' activity. Slow wave dysrhythmias are associated with motility disorders, including gastroparesis, offering an under-explored potential therapeutic target. While 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 per point). High-resolution electrical mapping (16×16 electrodes; 6×6 cm) was applied to define baseline and acute post-ablation activation patterns. Tissue damage was evaluated by H&E 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 per point. Gastric ablation may hold therapeutic potential for gastric electrical abnormalities in future.
Gastric ablation has demonstrated potential to induce conduction blocks and correct abnormal electrical activity (i.e., ectopic slow-wave propagation) in acute, intra-operative in-vivo studies. This study aimed to evaluate the safety and feasibility of gastric ablation to modulate slow-wave conduction after two-weeks 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 radio-frequency (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 post-ablation mapping. All animals recovered from the procedure, with no sign of perforation or other complication. Two weeks later, intra-operative 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 two-week timepoints, whereas all sham-controls had no conduction block. Histological and immunohistochemical evaluation showed that after two weeks of healing, the lesions were in the inflammation and early proliferation phase, 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 surrounding slow wave conduction capability.
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.
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