Simmonds Sam, Matthee Ashton, Dowrick Jarrah M, Taberner Andrew J, Du Peng, Angeli-Gordon Timothy R
Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.
High-Value Nutrition National Science Challenge, Auckland, New Zealand.
Am J Physiol Gastrointest Liver Physiol. 2024 Jul 1;327(1):G93-G104. doi: 10.1152/ajpgi.00018.2024. Epub 2024 May 21.
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 ( = 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 ( = 512) and spikes ( = 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 ( = 0.74, < 0.001) and duodenum ( = 0.42, < 0.001). Slow-wave and contractile amplitudes were correlated in the antrum ( = 0.48, < 0.001) and duodenum ( = 0.35, < 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. 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.
尽管胃十二指肠交界处(GDJ)的机电耦合是新型干预措施的一个靶点,但很少有生物标志物能支持肠道-脑相互作用障碍(DGBI)的诊断和治疗。由 Cajal 间质细胞(ICC)产生的节律性“慢波”和肌源性“尖峰”是支撑运动的生物电机制。在本研究中,将体内同步高分辨率电生理和阻抗平面测量与免疫组织化学相结合,以阐明 GDJ 的机电耦合。在获得伦理批准后,暴露了 12 头麻醉猪的 GDJ。将解剖学上特定的高分辨率电极阵列(256 个电极)应用于浆膜。将 EndoFLIP 导管(16 个电极;美敦力公司,明尼苏达州)置于腔内以估计直径。死后组织样本用 Masson 三色染色法和 Ano1 染色,以量化肌肉组织和 ICC。电标测记录了 512 个慢波和 1071 个尖峰。收缩与电活动模式平行。局部慢波和尖峰先于胃窦的节律性收缩和十二指肠的非节律性收缩。慢波和尖峰幅度在胃窦(r = 0.74,P < 0.001)和十二指肠(r = 0.42,P < 0.001)中呈正相关。慢波和收缩幅度在胃窦(r = 0.48,P < 0.001)和十二指肠(r = 0.35,P < 0.001)中呈正相关。胃窦和十二指肠不同的纵行和环行肌层总厚度分别为(2.8±0.9)mm 和(0.4±0.1)mm。在幽门处,肌层融合并增厚至(3.5±1.6)mm。与胃窦(4.2±3.0%)和十二指肠(5.3±2.8%)相比,幽门肌间 ICC 覆盖面积较小(1.5±1.1%)。对机电耦合和 ICC 活检的进一步表征可能会产生 DGBI 生物标志物。本研究将电标测、阻抗平面测量和组织学技术应用于胃十二指肠交界处,以阐明体内的机电耦合。胃窦末端和幽门括约肌的收缩与胃慢波有关。在十二指肠中,尖峰活动的爆发触发了振荡收缩。与相邻的胃窦和十二指肠相比,幽门处 Cajal 间质细胞相对稀少,推测这可防止胃窦和十二指肠慢波之间的耦合。