Mechanosensory properties in the human gastric antrum evaluated using B-mode ultrasonography during volume-controlled antral distension

The aims of this study were to evaluate gastric antral mechanical behavior and distension-induced sensorimotor responses in the human gastric antrum using transabdominal ultrasound scanning. Ten healthy volunteers underwent volume-controlled ramp inflation of a bag located in the antrum with volumes up to 125 ml. The active and passive circumferential tensions and stresses were calculated from measurements of pressure, diameter, and wall thickness before and during the administration of the anticholinergic drug butylscopolamine. The bag distensions elicited contractions in the antrum and sensory responses below the pain threshold. Butylscopolamine abolished the contractions and significantly reduced the sensory response. The length-tension diagram known from in vitro studies of smooth muscle strips could be reproduced as tension-volume diagrams in the human gastric antrum. The number of induced contractions and the contraction pressure amplitude (afterload) showed a parabolic behavior as function of the distension volume (preload), with maximum approximately at 70 ml. At the sensation threshold, the luminal circumference showed the lowest variation coefficient (13–25%), whereas the variation coefficient was more than 100% for the pressure, tensions, and stresses. We conclude that the muscle length-tension diagram and typical preload-afterload curves ad modem the Frank-Starling cardiac law can be obtained in the human gastric antrum. The sensory responses were most closely associated with the luminal circumference, indicating that the sensation during antral distension depends on deformation rather than on tension.

Enhancement of antral contractions and vagal afferent signaling with synchronized electrical stimulation

Gastric filling activates vagal afferents involved in peripheral signaling to the central nervous system (CNS) for food intake. It is not known whether these afferents linearly encode increasing contractions of the antrum during antral distension (AD). The aim of this study was to investigate effects of AD and electrically enhanced antral contractions on responses of vagal afferents innervating the antrum. Single-fiber recordings were made from the vagal afferents in anesthetized male Long-Evans rats. Antral contractions were measured with a solid-state probe placed in the antrum. A nonexcitatory electrical stimulation (NES) inducing no smooth muscle contractions was applied during the ascending phase of antral contractions to enhance subsequent antral contractions. Fifty-six fibers identified during AD (1 ml for 30 s) were studied through different types of mechanical stimuli. Under normal conditions, one group of fibers exhibited rhythmic firing in phase with antral contractions. Another group of fibers had nonrhythmic spontaneous firing. Responses of 15 fibers were tested with NES during multiple-step distension (MSD). NES produced a mean increase in antral contraction amplitude (177.1 ± 35.3%) and vagal afferent firing (21.6 ± 2.6%). Results show that both passive distension and enhanced antral contractions activate distension-sensitive vagal afferents. Responses of these fibers increase linearly to enhanced antral contraction induced by NES or MSD up to a distending volume of 0.6 ml. However, responses reached a plateau at a distending volume >0.8 ml. We concluded that enhanced contraction of the antrum can activate vagal afferents signaling to the CNS.

Impaired gastrocolonic response and peristaltic reflex in slow-transit constipation: role of 5-HT3 pathways

Colonic motility is modulated by the 5-hydroxytryptamine (5-HT)3-dependent gastrocolonic response and 5-HT3-independent peristaltic reflex. We compared descending colon tone responses to antral distension, duodenal lipid perfusion, and colonic distension after double-blind placebo or granisetron in 13 healthy volunteers and nine slow-transit constipated patients. Antral distension (100–300 ml) and duodenal lipids (3 kcal/min) evoked increases in colon tone in volunteers, which were blunted in constipated patients ( P < 0.05). Granisetron (10 μg/kg) reduced responses to antral distension and lipids in volunteers and to lipids in constipated patients ( P < 0.05). The ascending contraction of the peristaltic reflex was blunted in constipated patients ( P < 0.05), whereas descending responses were similar. Granisetron did not modify the peristaltic reflex. Colonic responses to bethanechol were similar in patients and volunteers. In conclusion, antral distension- and duodenal lipid-activated gastrocolonic responses and ascending contractions of the peristaltic reflex are impaired with slow-transit constipation with loss of both 5-HT3-dependent and -independent function. Thus abnormalities of neural reflex modulation of colonic motor function may play pathophysiological roles in slow-transit constipation.

Differential symptomatic and electrogastrographic effects of distal and proximal human gastric distension

Nausea and gastric dysrhythmias occur in conditions associated with gastric distension. The roles of distal and proximal gastric mechanoreceptors in these responses are unexplored. Because antral distension induces vomiting in animals and antral and fundic vagal afferent discharges differ, we hypothesized that distal gastric distension in humans leads to greater symptomatic and dysrhythmic responses than proximal distension. Symptoms and electrogastrograms were recorded in healthy humans during distal and proximal gastric distension with a barostat. Distal but not proximal distension induced nausea and a 747 ± 250% increase in dysrhythmic power ( P < 0.05), responses not affected by granisetron, indomethacin, or atropine, agents that block dysrhythmias in other settings. In the distal stomach, bloating and pain developed at lower pressures ( P < 0.05) not modified by granisetron, and compliance was significantly lower ( P < 0.05). In conclusion, gastric mechanoreceptor activation in the less-compliant distal stomach produces nausea and dysrhythmias via non-5-hydroxytryptamine3(5-HT3), non-prostaglandin-dependent, and noncholinergic pathways. Distal mechanoreceptor activation induces greater bloating and pain than proximal mechanoreceptor activation via 5-HT3-independent pathways.

Differential 5-HT3 mediation of human gastrocolonic response and colonic peristaltic reflex

Colonic motor function is modulated by extended and local neural reflexes involving unknown mediators. To test the role of serotonin (5-HT3) pathways, increases in colonic tone during antral distension and duodenal lipid perfusion (gastrocolonic responses) and changes in orad and caudad colonic tone in response to local colonic distension (peristaltic reflex) were measured after double-blind granisetron (10 μg/kg) or placebo infusion in healthy human volunteers. Antral distension evoked increases in colonic tone, which were blunted by granisetron ( P < 0.05) without effects on antral compliance. Intraduodenal lipid perfusion also evoked increased colonic tone, which was reduced by granisetron ( P < 0.05). In contrast, orad colonic contractions and caudad relaxations and contractions during colonic distension were unaffected by granisetron. In conclusion, 5-HT3 receptor antagonism blunts both the mechano- and chemoreceptor components of the human gastrocolonic response without altering antral compliance. In contrast, 5-HT3 pathways play no role in the ascending or descending components of the colonic peristaltic reflex. These findings demonstrate different roles for 5-HT3 receptors in the control of colonic motor function by the proximal gastrointestinal tract and by local neural reflexes.