Vincristine delays gastric emptying and gastrointestinal transit of liquid in awake rats

We evaluated the effects of vincristine on the gastrointestinal (GI) motility of awake rats and correlated them with the course of vincristine-induced peripheral neuropathy. Vincristine or saline was injected into the tail vein of male Wistar rats (180-250 g) on alternate days: 50 µg/kg (5 doses, N = 10), 100 µg/kg (2, 3, 4 and 5 doses, N = 49) or 150 µg/kg (1, 2, or 5 doses, N = 37). Weight and stool output were measured daily for each animal. One day after completing the vincristine treatment, the animals were fasted for 24 h, gavage-fed with a test meal and sacrificed 10 min later to measure gastric emptying (GE), GI transit and colon weight. Sensory peripheral neuropathy was evaluated by hot plate testing. Chronic vincristine treatments with total cumulative doses of at least 250 µg/kg significantly decreased GE by 31-59 percent and GI transit by 55-93 percent. The effect of 5 doses of vincristine (150 µg/kg) on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 µg/kg). Fecal output decreased up to 48 h after the fifth dose of vincristine (150 µg/kg). Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 µg/kg or after 3-5 doses of 150 µg/kg. This effect lasted for at least 2 weeks after the fifth dose. Chronic intravenous vincristine treatment delayed GE and GI transit of liquid. This effect correlated with the peak increase in colon weight but not with the pain threshold changes.

Sildenafil delays the intestinal transit of a liquid meal in awake rats

Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44) were treated (0.2 mL, iv) with sildenafil (4 mg/kg) or vehicle (0.01 N HCl). Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline) injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP) was monitored in a separate group of rats (N = 14). Data (medians within interquartile ranges) were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6) vs 2.9 (2.7-3.1); 3.8 (3.4-4.0) vs 2.9 (2.5-3.1), and 4.3 (3.9-4.5) vs 3.4 (3.2-3.7), respectively; P < 0.05). MAP was unchanged in vehicle-treated rats but decreased by 25 percent (P < 0.05) within 10 min after sildenafil injection. In conclusion, besides transiently decreasing MAP, sildenafil delays the intestinal transit of a liquid test meal in awake rats.

Variations in gastric compliance induced by acute blood volume changes in anesthetized rats

The impact of acute volume imbalances on gastric volume (GV) was studied in anesthetized rats (250-300 g). After cervical and femoral vessel cannulation, a balloon catheter was positioned in the proximal stomach. The opposite end of the catheter was connected to a barostat with an electronic sensor coupled to a plethysmometer. A standard ionic solution was used to fill the balloon (about 3.0 ml) and the communicating vessel system, and to raise the reservoir liquid level 4 cm above the animals' xiphoid appendix. Due to constant barostat pressure, GV values were considered to represent the gastric compliance index. All animals were monitored for 90 min. After a basal interval, they were randomly assigned to normovolemic, hypervolemic, hypovolemic or restored protocols. Data were compared by ANOVA followed by Bonferroni's test. Mean arterial pressure (MAP), central venous pressure (CVP) and GV values did not change in normovolemic animals (N = 5). Hypervolemic animals (N = 12) were transfused at 0.5 ml/min with a suspension of red blood cells in Ringer-lactate solution with albumin (12.5 ml/kg), which reduced GV values by 11.3 percent (P<0.05). Hypovolemic rats (N = 12) were bled up to 10 ml/kg, a procedure that increased GV values by 15.8 percent (P<0.05). In the restored group (N = 12), shed blood replacement brought GV values back to basal levels in bled animals (P>0.05). MAP and CVP values increased (P<0.05) after hypervolemia but decreased (P<0.05) with hypovolemia. In conclusion, blood volume level modulates gastric compliance, turning the stomach into an adjustable reservoir, which could be part of the homeostatic process to balance blood volume

Decreased gastric emptying and gastrointestinal and intestinal transits of liquid after complete spinal cord transection in awake rats

We studied the effect of complete spinal cord transection (SCT) on gastric emptying (GE) and on gastrointestinal (GI) and intestinal transits of liquid in awake rats using the phenol red method. Male Wistar rats (N = 65) weighing 180-200 g were fasted for 24 h and complete SCT was performed between C7 and T1 vertebrae after a careful midline dorsal incision. GE and GI and intestinal transits were measured 15 min, 6 h or 24 h after recovery from anesthesia. A test meal (0.5 mg/ml phenol red in 5 percent glucose solution) was administered intragastrically (1.5 ml) and the animals were sacrificed by an iv thiopental overdose 10 min later to evaluate GE and GI transit. For intestinal transit measurements, 1 ml of the test meal was administered into the proximal duodenum through a cannula inserted into a gastric fistula. GE was inhibited (P<0.05) by 34.3, 23.4 and 22.7 percent, respectively, at 15 min, 6 h and 24 h after SCT. GI transit was inhibited (P<0.05) by 42.5, 19.8 and 18.4 percent, respectively, at 15 min, 6 h and 24 h after SCT. Intestinal transit was also inhibited (P<0.05) by 48.8, 47.2 and 40.1 percent, respectively, at 15 min, 6 h and 24 h after SCT. Mean arterial pressure was significantly decreased (P<0.05) by 48.5, 46.8 and 41.5 percent, respectively, at 15 min, 6 h and 24 h after SCT. In summary, our report describes a decreased GE and GI and intestinal transits in awake rats within the first 24 h after high SCT

Variations in gastric emptying of liquid elicited by acute blood volume changes in awake rats

We have observed that acute blood volume expansion increases the gastroduodenal resistance to the flow of liquid in anesthetized dogs, while retraction decreases it (Santos et al. (1991) Acta Physiologica Scandinavica, 143:261-269). This study evaluates the effect of blood volume expansion and retraction on the gastric emptying of liquid in awake rats using a modification of the technique of Scarpignato (1980) (Archives Internationales de Pharmacodynamie et de Therapie, 246:286-294). Male Wistar rats (180-220g( were fasted for 16 h with water ad libitum and 1.5 ml of the test meal (0.5 mg/ml phenol red solution in 5 percent glucose) was delivered to the stomach immediately after random submission to one of the following protocols: 1) normovolemic control (N=22), 2) expansion (N=72) by intravenous infusion (1 ml/min) of Ringer-bicarbonate solution, volumes of 1,2,3 or 5 percent body weight, or 3) retraction (N-22) by controlled bleeding (1.5 ml/100g). Gastric emptying of liquid was inhibited by 19-51.2 percent (P<0.05) after blood volume expansion (volumes of 1,2,3 or 5 percent body weight). Blood volume expansion produced a sustained increase in central venous pressure while mean arterial presure was transiently increased during expansion (P<0.05). Blood volume retraction increased gastric emptying by 28.5-49.9 percent (P<0.05) and decreased central venous pressure and mean arterial pressure (P<0.05). Infusion of the shed blood 10 min after bleeding reversed the effect of retraction on gastric emptying. These findings suggest that gastric emptying of liquid is subject to modulation by the blood volume.

Acute blood volume expansion delays the gastrointestinal transit of a charcoal meal in awake rats

The present study evaluates the effect of blood volume expansion on the gastrointestinal transit of a charchoal meal (2.5 ml of an aqueous suspension consisting of 5 percent charcoal and 5 percent gum arabic) in awake male Wistar rats (200-270 g). On the day before the experiments, the rats were anesthetized with ether, submitted to left jugular vein cannulation and fasted with water ad libitum until 2 h before the gastrointestinal transit measurement. Blood volume expansion by iv infusion of 1 ml/min Ringer bicarbonate in volumes of 3, 4 or 5 percent body weight delayed gastrointestinal transit at 10 min after test meal administration by 21.3-26.7 percent (P<0.05), but no effect was observed after 1 or 2 percent body weight expansion. The effect of blood volume expansion (up to 5 por cento body weight) on gastrointestinal transit lasted for at least 60 min (P<0.05). Mean arterial pressure increased transiently and central venous pressure increased and hematocrit decreased (P<0.05). Subdiaphragmatic vagotomy and yohimbine (3 mg/kg) prevented the delay caused by expansion on gastrointestinal transit, while atropine (0.5 mg/kg), L-NAME (2 mg/kg), hexamethonium (10 mg/kg), prazosin (1 mg/kg) or propranolol (2 mg/kg) were ineffective. These data show that blood volume expansion delays the gastrointestinal transit of a charcoal meal and that vagal and yohimbine-sensitive pathways appear to be involved in this phenomenon. The delay in gastrointestinal transit observed here, taken together with the modifications of gastrointestinal permeability to salt and water reported by others, may be part of the mechanisms involved in liquid excess management

Effect of pyloroplasty and fundectomy on the delay of gastric emptying and gastrointestinal transit of liquid elicited by acute blood volume expansion in awake rats

We evaluated the effects of fundectomy and pyloroplasty on the delay of gastric emptying (GE) and gastrointestinal (GI) transit of liquid due to blood volume (BV) expansion in awake rats. Male Wistar rats (N=76, 180-250 g) were first submitted to fundectomy (N=26), Heinecke-Mikulicz pyloroplasty (N=25) or SHAM laparotomy (N=25). After 6 days, the left external jugular vein was cannulated and the animals were fasted for 24 h with water ad libitum. The test meal was administered intragastrically (1.5 ml of a phenol red solution, 0.5 mg/ml in 5 percent glucose) to normovolemic control animals and to animals submitted to BV expansion (Ringer-bicarbonate, iv infusion, 1 ml/min, volume up to 5 percent body weight). BV expansion decreased GE and GI transit rates in SHAM laparotomized animals by 52 and 35.9 percent (P<0.05). Fundectomy increased GE and GI transit rates by 61.1 and 67.7 percent (P<0.05) and prevented the effect of expansion on GE but not on GI transit (13.9 percent reduction, P<0.05). Pyloroplasty also increased GE and GI transit rates by 33.9 and 44.8 percent (P<0.05) but did not prevent the effect of expansion on GE or GI transit (50.7 and 21.1. percent reduction, P<0.05). Subdiaphragmatic vagotomy blocked the effect of expansion on GE and GI transit in both SHAM laparotomized animals and animals submitted to pyloroplasty. In conclusion 1) the proximal stomach is involved in the GE delay due to BV expansion but is not essential for the establishment of a delay in GI transit, which suggests the activation of intestinal resistances, 2) pyloric modulation was not apparent, and 3) vagal pathways are involved.

Gastroduodenal resistance and neural mechanisms involved in saline flow decrease elicited by acute blood volume expansion in anesthetized rats

We have previously demonstrated that blood volume (BV) expansion decreases saline flow through the gastroduodenal (GD) segment in anesthetized rats (Xavier-Neto J, dos Santos AA & Rola FH (1990) Gut, 31: 1006-1010). The present study attempts to identify the site(s) of resistance and neural mechanisms involved in this phenomenon. Male Wistar rats (N = 97,200-300 g) were surgically manipulated to create four gut circuits: GD, gastric, pyloric and duodenal. These circuits were perfused under barostatically controlled pressure (4 cmH2O). Steadysate changes in flow were taken to reflect modifications in circuit resistances during three periods of time: normovolemic control (20 min), expansion (10-15 min), and expanded (30 min). Perfusion flow rates did not change in normovolemic control animals over a period of 60 min. BV expansion (Ringer bicarbonate, 1 ml/min up to 5 percent body weight) significantly (p<0.05) reduced perfusion flow in the GD (10.3 + 0.5 to 7.6 + 0.6 ml/min), pyloric (9.0 + 0.6 to 5.6 + 1.2 ml/min) and duodenal (10.8 + 0.4 to 9.0 + 0.6 ml/min) circuits, but not in the gastric circuit (11.9 + 0.4 to 10.4 + 0.6 ml/min). Prazosin (1 mg/kg) and yohimbine (3 mg/kg) prevented the expansion effect on the duodenal but not on the pyloric circuit. Bilateral cervical vagotomy prevented the expansion effect on the pylorus during the expansion but not during the expanded period and had no effect on the duodenum. Atropine (0.5 mg/kg), hexamethonium (10 mg/kg) and propranolol (2 mg/kg) were ineffective on both circuits. These results indicate that 1) BV expansion increases the GD resistance to liquid flow, 2) pylorus and duodenum are important sites of resistance, and 3) yohimbine and prazosin prevented the increase in duodenal resistance and vagotomy prevented it partially in the pylorus.

Acute extracellular fluid volume changes increase ileocolonic resistancce to saline flow in anesthetized dogs

We determined the effect of acute extracellular fluid volume changes on saline flow through 4 gut segments (ileocolonic, ileal, ileocolonic sphincter and proximal colon), perfused at constant pressure in anesthetized dogs. Two different experimental protocols were used: hypervolemia (iv saline infusion, 0.9 per cent NaCl, 20 ml/min, volume up to 5 per cent body weight) and controlled hemorrhage (up to a 50 per cent drop in mean arterial pressure). Mean ileocolonic flow (N = 6) was gradually and significantly decreased during the expansion (17.1 per cent P<0.05) and expanded (44.9 per cent, P<0.05) periods while mean ileal flow (N = 7) was significantly decreased only during the expanded period (38 per cent, P<0.05). Mean colonic flow (N = 7) was decreased during expansion (12 per cent, P<0.05) but returned to control levels during the expanded period. Mean ileocolonic sphincter flow (N = 6) was not significantly modified. Mean ielocolonic flow (n = 10) was also decreased after hemorhage (retracted period) by 17 per cent (P<0.05), but saline flow was not modified in the other separate circuitis (N = 6,5 and 4 for ileal, ileocolonic sphincter and colonic groups, respectively). The expansion effect was blocked by atropine (0.5 mg/kg, iv) both on the ileocolonic (N = 6) and ileal (N = 5) circuits. Acute extracellular fluid volume retraction and expansion increased the lower gastrointestinal resistances to saline flow. These effects, which could physiologically decrease the liquid volume being supplied to the colon, are possible mechanisms activated to acutely balance liquid volume deficit and excess.

Effects of acute volemic changes on jejunal compliance in dogs

1. Jejunal compliance (deltaV/deltaP) was calculated from the intraluminal pressures measured in anesthetized dogs in an in situ upper jejunal pouch (40-50-ml capcity) with intraluminal volumes of 10, 20, 30, 40 and 50 ml of fisotonic saline. 2. Measurements were made in the same animal during and after acute sequential alterations of the extracellular fluid (ECF) volume obtained by: a) acute intravenous (iv) infusion of isotonic saline, b) acute hemorrhage, and c) reinfusion of isotonic saline. 3. Expansion of the ECF volume caused a significant, reversible downward shift of the compliance curve, i.e., the jejunal pouch became less receptive to liquid distension. After saline infusion was discontinued, complicance gradually returned to control levels. 4. Acute loss a substantial volume of blood after ECF expansion gradually shifted the complicance curve upwards to levels significantly diferent from control, indicating that retraction of the ECF volume made the jejunal pouch more receptive to liquid distension. 5. Reinfusion of bled animals with saline rather than autologous blood also induced a significant decrease in jejunal complicance to below control levels. 6. The jejunal pouch as a suitable preparation for monitoring in vivo modifications of compliance induced by acute changes in ECF volume, especially when it was nearly "half-full" (i.e., filled with 20 ml), suggesting a critical relationship between the volume capacity of the pouch and its fluid content. 7. These results suggest that the modulation of the jejunal portion os small intestine compliance is involved in the processes that balance the ECF volume during acute life-threatening situations such as accidental hyperhydration or hemorrhage

Acute changes in extracellular fluid volume modify the antroduodenal flow of saline in dogs: a possible physiological role

The antroduodenal (AD) flow of saline was measured in anesthetized dogs following two different protocols of acute changes in extracellular fluid (ECF) volume, ECF expansion by in infusion of saline before or after hemorrhage decreased the AD flow; conversely, hemorrhage before or after expansion increased flow. These alternating modifications in the AD flow are independent of the sequence of volemic changes and may constitue part of the homeostatic responses of the gut to confront life-thratening situations such as accidental hyperhydration or hemorrhage