Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in Patients With Chronic Unexplained Nausea and Vomiting
Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in Patients With Chronic Unexplained Nausea and Vomiting
复制标题
DOI：
10.1053/j.gastro.2015.04.003
复制
发表时间：
2015-07-01
期刊：
影响因子：
29.4
通讯作者：
O'Grady, Gregory
中科院分区：
文献类型：
--
作者：
Angeli, Timothy R.;Cheng, Leo K.;O'Grady, Gregory
背景与目的：慢性不明原因恶心呕吐（CUNV）是一种原因不明的致衰弱性疾病。CUNV的症状与胃轻瘫的症状基本重叠，因此这些疾病可能具有共同的病理生理特征。我们研究了这一假设，定量密度的卡哈尔间质细胞（ICC）和映射慢波异常与CUNV患者与对照组。方法：临床数据和胃活检标本收集自9名连续患者，这些患者在密西西比大学医学中心接受治疗，具有至少6个月的连续CUNV症状，但胃排空正常，并收集自9名对照组（无胃肠道疾病或糖尿病的个体）。对组织样本进行ICC计数和超微结构分析。通过高分辨率电标测（256个电极; 36 cm（2））确定慢波传播曲线。将CUNV患者的结果与对照组以及先前通过相同方法研究的胃轻瘫患者的结果进行比较。研究结果：CUNV患者的ICC比对照组少（平均值分别为3.5和5.6个小体/视野; P <0.05），其余ICC有轻度超微结构异常。慢波心律失常在所有9名CUNV受试者中被确定，而9名对照者中仅1名。心律失常包括起始异常（稳定的异位起搏器，不稳定的局灶性活动）和传导异常（逆行传播，波前碰撞，传导阻滞和折返），在心动过缓，正常（范围，2.4-3.7周期/分钟）和心动过速频率下运行;心律失常显示速度各向异性（平均，纵向3.3 mm/s vs周向7.6 mm/s; P <0.01）。与胃轻瘫患者相比，CUNV患者的ICC消耗较少（平均值分别为3.5和2.3个/视野; P <0.05），但慢波节律障碍在两组之间相似。结论：本研究确定了CUNV患者的细胞和生物电异常，包括慢波折返的识别。CUNV的病理生理特征与胃轻瘫相似，提示它们可能是同一疾病的谱。这些发现为CUNV的发病机制提供了新的见解，并可能有助于为未来的治疗提供信息。
BACKGROUND & AIMS: Chronic unexplained nausea and vomiting (CUNV) is a debilitating disease of unknown cause. Symptoms of CUNV substantially overlap with those of gastroparesis, therefore the diseases may share pathophysiologic features. We investigated this hypothesis by quantifying densities of interstitial cells of Cajal (ICCs) and mapping slow-wave abnormalities in patients with CUNV vs controls. METHODS: Clinical data and gastric biopsy specimens were collected from 9 consecutive patients with at least 6 months of continuous symptoms of CUNV but normal gastric emptying who were treated at the University of Mississippi Medical Center, and from 9 controls (individuals free of gastrointestinal disease or diabetes). ICCs were counted and ultrastructural analyses were performed on tissue samples. Slow-wave propagation profiles were defined by high-resolution electrical mapping (256 electrodes; 36 cm(2)). Results from patients with CUNV were compared with those of controls as well as patients with gastroparesis who were studied previously by identical methods. RESULTS: Patients with CUNV had fewer ICCs than controls (mean, 3.5 vs 5.6 bodies/field, respectively; P < .05), with mild ultrastructural abnormalities in the remaining ICCs. Slow-wave dysrhythmias were identified in all 9 subjects with CUNV vs only 1 of 9 controls. Dysrhythmias included abnormalities of initiation (stable ectopic pacemakers, unstable focal activities) and conduction (retrograde propagation, wavefront collisions, conduction blocks, and re-entry), operating across bradygastric, normal (range, 2.4-3.7 cycles/min), and tachygastric frequencies; dysrhythmias showed velocity anisotropy (mean, 3.3 mm/s longitudinal vs 7.6 mm/s circumferential; P < .01). ICCs were less depleted in patients with CUNV than in those with gastroparesis (mean, 3.5 vs 2.3 bodies/field, respectively; P < .05), but slow-wave dysrhythmias were similar between groups. CONCLUSIONS: This study defined cellular and bioelectrical abnormalities in patients with CUNV, including the identification of slow-wave re-entry. Pathophysiologic features of CUNV were observed to be similar to those of gastroparesis, indicating that they could be spectra of the same disorder. These findings offer new insights into the pathogenesis of CUNV and may help to inform future treatments.