Characterization of the off response to electrical field stimulation in gallbladder smooth muscle.

BACKGROUND: Low-frequency electrical stimulation of intramural nerves of gut smooth muscle produces an "off response," that is, a contraction that occurs after electrical field stimulation (EFS) of the intramural nerves is stopped. The off response coincides with a depolarization of the muscle following an EFS-induced hyperpolarization of that muscle. The aims of our study were to determine if the off response is present in gallbladder smooth muscle and to determine the mechanisms involved in this nerve-mediated response. MATERIALS AND METHODS: Gallbladder strips from opossums were placed in Krebs solution and passed through bipolar ring electrodes for EFS of intramural nerves, and isometric force measurements were recorded. Dose-response curves were determined with N(G)-nitro-L-arginine (L-NNA) a competitive inhibitor of nitric oxide (NO) synthase; 1H-¿1,2,4oxadiazolol¿4, 3aquinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase; and oxyhemoglobin, a scavenger of nitric oxide. RESULTS: A contraction termed the off response occurred shortly after EFS ended. The off response was abolished with tetrodotoxin and atropine. The amplitude of the off response increased with increasing voltage. The amplitude of the off response decreased by 41% with L-NNA 1.5 mM. Preincubation of the tissue with L-arginine (1 mM) prevented the inhibition of amplitude seen with L-NNA. The amplitude of the off response decreased by 43% with oxyhemoglobin (40 microM) and by 56% with ODQ (250 microM). CONCLUSION: We conclude that the off response is present in gallbladder smooth muscle after low-frequency EFS. NO may be a mediator of this off response and of nonadrenergic noncholinergic responses in gallbladder smooth muscle.

Gastric emptying of liquids and postprandial pancreatobiliary secretion are temporarily impaired during endotoxemia.

The aims of our study were to determine mechanisms by which pancreatobiliary secretion is altered during endotoxemia. Dogs underwent placement of duodenal perfusion and aspiration catheters and antral manometry catheters. Gastric emptying of liquids, antral motility, output of bile acids and amylase, and serum levels of enteric hormones were determined after ingestion of a 360-kcal mixed-nutrient liquid meal. Each dog was then given a single dose of E. coli lipopolysaccharide (200 microg/kg, intravenously) and the studies repeated for the next three days. Endotoxin slowed gastric emptying of liquids and decreased amylase output for two days. Bile acid output was decreased on postendotoxin day 1. Pancreatic polypeptide alone was decreased on postendotoxin day 1. We conclude that the decrease in pancreatobiliary output is probably due to decreased nutrient flow into the duodenum and not due to decreased production of hormones that influence pancreatobiliary secretion. The delayed gastric emptying, decreased pancreatobiliary output, and decreased postprandial levels of pancreatic polypeptide suggest diminished vagal output as a possible explanation for the effects of endotoxin on upper gut function.

Changes in intestinal transit and absorption during endotoxemia are dose dependent.

BACKGROUND: Septic patients are often intolerant of enteral feedings due to a combination of motility disturbances and impaired absorptive function. Our laboratory has previously demonstrated that endotoxemia results in rapid intestinal transit and decreased jejunal absorption of water, electrolytes, and glucose. We hypothesized that the changes in jejunal transit and absorption during endotoxemia may be dependent on the dose of endotoxin. MATERIALS AND METHODS: Under general anesthesia, rats underwent placement of an internal jugular line, a femoral arterial line, and a 20-cm jejunal Thiry-Vella loop. The jejunal segment was perfused with an isotonic solution containing polyethylene glycol. For 90 min, baseline measurements of blood pressure, heart rate, jejunal absorption of water, electrolytes, and glucose, and jejunal transit were made. Following this baseline period I, rats were given 0.9% NaCl (1 ml/kg) or one of three doses of Escherichia coli lipopolysaccharide (0.5, 1.0, or 5.0 mg/kg). Studies were then repeated for an additional 90 min. RESULTS: Changes in blood pressure and heart rate were similar among the four groups of animals. Endotoxin decreased water and glucose flux, increased potassium flux, and quickened intestinal transit in a dose-dependent fashion. CONCLUSIONS: We conclude that endotoxemia causes dose-dependent changes in jejunal transit and absorption. The effects of increasing doses of endotoxin on jejunal absorptive and motor function do not appear to be mediated by changes in blood pressure or heart rate.

Effect of endotoxin on canine colonic motility and transit.

Diarrhea is a common problem in patients who have episodes of sepsis and are being fed enterally. Endotoxemia results in gastrointestinal motor dysfunction characterized by slowed gastric emptying and rapid intestinal transit; however, the effect of endotoxin on colonic motility is unknown. The aim of our study was to determine the effects of a single sublethal dose of endotoxin on colonic motility and transit. Seven dogs underwent construction of a 50 cm colonic Thiry-Vella fistula. Five manometry catheters were sewn into the colonic lumen at 8 cm intervals along the fistula. Following recovery, the fistula was perfused with an isotonic solution at 2.9 ml/min, and fasting and postprandial colonic motility was determined. Liquid transit was assessed by bolus of a nonabsorbable marker instilled into the proximal end of the Thiry-Vella fistula. Recordings of gastrointestinal contractile activity were made digitally to determine contractile frequencies and motility indexes. Following completion of the baseline studies, each dog was given a single dose of E. coli lipopolysaccharide, 200 microgram/kg intravenously, and studies were repeated daily for the next 3 days. Endotoxin doubled the fasting colonic contractile frequency on postendotoxin day 1 and also increased motility indexes on that same day. Fasting motility indexes and contractile activity were decreased on postendotoxin days 2 and 3. The postprandial frequency of contractions and motility indexes were decreased on postendotoxin day 3. Fasting colonic liquid transit was rapid on postendotoxin day 1, whereas postprandial liquid transit was rapid on both postendotoxin days 1 and 2. Endotoxin temporarily speeds liquid transit and increases both the frequency and strength of colonic contractions. These effects may contribute to the diarrhea that occurs during episodes of sepsis.

Endotoxin temporarily impairs canine colonic absorption of water and sodium.

Diarrhea is a common manifestation of sepsis. We hypothesized that endotoxin may impair colonic absorption of water and electrolytes, an effect which may be related to altered liquid transit in the colon. Five dogs underwent construction of 50-cm colonic Thiry-Vella fistulas (TVF). Following recovery, absorption studies were performed by perfusing the TVF with an isotonic solution at 2.9 ml/min containing polyethylene glycol (5 g/L). Fasting and postprandial colonic absorption of water, electrolytes, and glucose were determined. Liquid transit was assessed by bolus of a nonabsorbable marker (PSP) instilled into the proximal end of the TVF. Following completion of the baseline studies, each dog was given a single dose of Escherichia coli lipopolysaccharide 200 micrograms/kg i.v. and the studies were repeated daily for the next 3 days. Following endotoxin bolus, colonic absorption of water and sodium were decreased during fasting, while postprandial colonic absorption of water was also decreased. Colonic absorption of water and sodium returned to baseline values on postendotoxin day 2. Colonic secretion of potassium was decreased on postendotoxin days 1 and 3 in both the fasting and the fed periods. Fasting and postprandial liquid transit was also rapid on postendotoxin day 1, which correlated with the decreased absorption seen on that day. Liquid transit returned to baseline values on postendotoxin day 2. We conclude that endotoxin temporarily impairs postprandial colonic absorption, which may be due to the rapid liquid transit that occurs. These effects may contribute to the diarrhea seen during and after septic episodes.

Endotoxin temporarily impairs canine jejunal absorption of water, electrolytes, and glucose.

Enteral feeding during and after episodes of sepsis may be beneficial. The aim of our study was to determine the effects of a single sublethal dose of endotoxin on canine jejunal absorption. Following a 240 kcal liquid meal, absorption studies were performed in eight dogs with 75 cm jejunal Thiry-Vella fistulas. These fistulas were perfused with an isotonic solution containing polyethylene glycol to calculate absorption. Each dog was then given a single dose of Escherichia coli lipopolysaccharide, 200 microg/kg intravenously, and the studies were repeated for the next 3 days. Following endotoxin bolus infusion, net absorption of water, electrolytes, and glucose was decreased for 2 days and returned to baseline values on postendotoxin day 3. A single sublethal dose of endotoxin temporarily impairs canine jejunal absorption. Although enteral feeding may be advantageous, jejunal absorption may be temporarily impaired following an episode of endotoxemia.

The effect of endotoxin on canine jejunal motility and transit.

Intestinal transit is rapid during endotoxemia; however, little is known regarding the small intestinal motility changes which produce this rapid intestinal transit. The aim of our study was to determine the degree and duration of disrupted jejunal transit, and changes in jejunal motility following a sublethal dose of endotoxin. Eight dogs underwent construction of jejunal Thiry-Vella fistulas (TVF) with manometry catheters to record motility along the TVF. Following recovery, a 240-kcal liquid meal was given and the TVF was perfused with an isotonic solution. Liquid transit was assessed by bolus of a nonabsorbable marker instilled into the proximal end of the TVF. Recordings of gastrointestinal contractile activity were made digitally to determine postpandial motility. Following completion of the baseline studies, each dog was given a single dose of Escherichia coli lipopolysaccharide (200 micrograms/kg, iv) and the postprandial studies were repeated for the next 3 days. Endotoxin decreased the frequency of jejunal contractions for 2 days while the strength of jejunal contractions was diminished for 1 day. Jejunal transit of liquids was rapid on Postendotoxin Day 1. The rapid transit was associated with a greater percentage of single pressure waves propagating aborally on Postendotoxin Day 1 than the baseline percentages established prior to endotoxin. We conclude that endotoxemia temporarily disrupts postprandial jejunal motility and transit. The rapid liquid intestinal transit seen with endotoxemia may be due to changes in contractile propagation.