Analysis of pacemaker activity in the human stomach

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Abstract

Non–technical summary

What is known about gastric electrophysiology and used in motility clinics throughout the world is mostly deduced from animal studies and extracellular recordings from human patients. Extracellular recording from gastrointestinal muscles, however, is prone to extensive motion artifact, and it is not clear that animal models can be translated directly to human physiology. Therefore, we have performed a detailed analysis of electrical activity from carefully mapped specimens of gastric muscle removed from humans during surgery for gastric cancers. Our data show several important differences in electrical activity recorded with intracellular microelectrodes and accepted gastric electrophysiological dogma. We observed ongoing electrical slow wave activity in the gastric fundus; we also found no evidence for a slow wave frequency gradient. Muscles from all regions through the thickness of the muscularis demonstrated intrinsic pacemaker activity, and this corresponded with the widespread distribution of pacemaker cells.

Extracellular electrical recording and studies using animal models have helped establish important concepts of human gastric physiology. Accepted standards include electrical quiescence in the fundus, 3 cycles per minute (cpm) pacemaker activity in corpus and antrum, and a proximal–to–distal slow wave frequency gradient. We investigated slow wave pacemaker activity, contractions and distribution of interstitial cells of Cajal (ICC) in human gastric muscles. Muscles were obtained from patients undergoing gastric resection for cancer, and the anatomical locations of each specimen were mapped by the operating surgeon to 16 standardized regions of the stomach. Electrical slow waves were recorded with intracellular microelectrodes and contractions were recorded by isometric force techniques. Slow waves were routinely recorded from gastric fundus muscles. These events had similar waveforms as slow waves in more distal regions and were coupled to phasic contractions. Gastric slow wave frequency was significantly greater than 3 cpm in all regions of the stomach. Antral slow wave frequency often exceeded the highest frequency of pacemaker activity in the corpus. Chronotropic mechanisms such as muscarinic and prostaglandin receptor binding, stretch, extracelluar Ca2+ and temperature were unable to explain the observed slow wave frequency that exceeded accepted normal levels. Muscles from all regions through the thickness of the muscularis demonstrated intrinsic pacemaker activity, and this corresponded with the widespread distribution in ICC we mapped throughout the tunica muscularis. Our findings suggest that extracellular electrical recording has underestimated human slow wave frequency and mechanisms of human gastric function may differ from standard laboratory animal models.

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