Abnormal Initiation and Conduction of Slow-Wave Activity in Gastroparesis, Defined by High-Resolution Electrical Mapping

Abstract

Background & Aims Interstitial cells of Cajal (ICC) generate slow waves. Disrupted ICC networks and gastric dysrhythmias are each associated with gastroparesis. However, there are no data on the initiation and propagation of slow waves in gastroparesis, because research tools have lacked spatial resolution. We applied high-resolution electrical mapping to quantify and classify gastroparesis slow-wave abnormalities in spatiotemporal detail. Methods Serosal HR mapping was performed, using flexible arrays (256 electrodes; 36 cm2), at stimulator implantation in 12 patients with diabetic or idiopathic gastroparesis. Data were analyzed by isochronal mapping, velocity and amplitude field mapping, and propagation animation. ICC numbers were determined from gastric biopsies. Results Mean ICC counts were reduced in patients with gastroparesis (2.3 vs 5.4 bodies/field; P<.001). Slow-wave abnormalities were detected by HR mapping in 11/12 patients. Several new patterns were observed and classified as ‘abnormal initiation’ (10/12; stable ectopic pacemakers or diffuse focal events; median 3.3 c/min, range 2.1-5.7), or ‘abnormal conduction’ (7/10; reduced velocities or conduction blocks; median 2.9 c/min; range 2.1-3.6). Circumferential conduction emerged during aberrant initiation or incomplete block and was associated with velocity elevation (7.3 vs 2.9 mm s−1; P=.002) and increased amplitudes beyond a low base value (415 vs 170 μV; P=.002). Conclusions HR mapping revealed new categories of abnormal human slow-wave activity. Abnormalities of slow-wave initiation and conduction occur in gastroparesis, often at normal frequency, which could be missed by tests that lack spatial resolution. Irregular initiation, aberrant conduction, and low amplitude activity could contribute to the pathogenesis of gastroparesis.

Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs

“…65 However, this dysrhythmia was not always reflected in our quantitative measurements, as regularity is not actively measured in the program. A study on slow waves in gastroparesis has made a similar observation 71 ; it was found that measuring only frequency did not adequately reflect the dysfunctional irregularity of slow waves -in this case, it was found that abnormal initiation and conduction of slow waves occurred. If the software could be improved further to analyze regularity of contractions, this would add an extra dimension to quantitative analysis.…”

“…[94][95][96] Lower numbers of ICC have been found in gastroparesis, 71 slow-transit constipation, 94,95 and intestinal pseudo-obstruction. 91 In achalasia, increased number of organelles (smooth endoplasmic reticulum and mitochondria) has been found in ICC located in the lower esophageal sphincter, possibly contributing to overactive contraction.…”

Numerical metrics for automated quantification of interstitial cell of Cajal network structural properties

“…However, at the same time, there are also patients with significant symptoms but apparently normal ICC numbers [11,12]. This may not only reflect primary pathological involvement of other cell types including macrophages and neurons, but also may reflect changes to ICC networks that affect function not captured by the relatively simplistic measures currently used.…”

“…However, in studies where the organ is likely to exhibit physical changes, such as tissue distension in pseudo-obstruction and similar animal models, additional measures should be taken into account for changes in organ size when applying these metrics on the imaging data. One such strategy, as employed previously [11], is to stain for another unaffected cell type, for example, smooth muscle nuclei as well as for ICC, and then the nuclei counts can be used as a normalizing factor to ensure standardized structural comparison between different tissue samples. On the other hand, stretch induced by tissue handling in the experimental procedure may still be present, and hence may have influenced some of the numerical metric values.…”

“…ICC loss and injury is now a major research focus as it is recognized as a hallmark of several GI motility disorders [10], including gastroparesis [11,12], slow transit constipation [13,14] and intestinal pseudo-obstruction [15,16]. In addition, progressive depletion of ICC is known to occur as part of normal ageing [17].…”