Sensory and inflammatory colonic changes induced by vincristine in distinct rat models of colitis.

Preclinical and clinical studies show that gastrointestinal (GI) inflammation can evoke sensory changes occasionally far from the original inflammatory site. Animal models of colitis with either trinitrobenzenesulphonic acid (TNBS) or mustard oil (MO) produce distinct patterns of somatic and visceral sensory changes. We evaluated the effects of four doses of i.v. vincristine 150 µg kg(-1) (total of 600 µg kg(-1) ) treatment on the somatic (thermal nociceptive threshold) and colonic (morphological) changes induced by TNBS or MO in rats. TNBS and MO groups were further submitted to vincristine or saline pretreatments. TNBS induced somatic hypersensitivity, while MO induced somatic hyposensitivity (P < 0.05) when compared to the saline and ethanol control groups. Vincristine per se induced somatic hypersensitivity (P < 0.05). This effect was enhanced by TNBS and reversed by MO treatments. Although vincristine increased the colitis area (colonic weight length(-1) ratio) and the Morris' score in TNBS-treated rats, it did not alter the colitis area and even lowered the Morris' score in MO-treated rats. Compared to the saline (control) group, vincristine did not alter the colonic microscopic pattern. However, such lesions scores are higher (P < 0.05) in colitis groups induced by TNBS and MO, pretreated or not with vincristine. In conclusion, the somatic changes induced by different models of experimental colitis are diverse and modulated differently by vincristine.

Atrial stretch increases the gastric tonus of anesthetized rats.

AIMS: We assessed the effects of right atrial stretch on gastric tone and neuro-humoral pathways involved in this phenomenon. MAIN METHODS: Anesthetized male rats were submitted for monitoring of the mean arterial pressure (MAP) and central venous pressure (CVP). A balloon catheter positioned into the stomach monitored by plethysmography the gastric volume (GV). All rats were monitored for 55-min. After the first 20-min of monitoring (basal period), rats were either submitted to a 5-min interval of atrial stretch (AS) or maintained as controls. An intra-atrial balloon catheter was distended with 30, 50, or 70 microL of saline. GV and hemodynamic data were also monitored for a further 30-min. Another set of rats, either previously submitted to subdiaphragmatic vagotomy or splanchnicectomy plus celiac ganglionectomy or maintained as controls (sham), were also submitted to AS. Each subset consisted of six rats. The plasma level of the atrial natriuretic peptide (ANP) was measured in another group of rats. Data were compared by ANOVA followed by Bonferroni's test. KEY FINDINGS: In control rats, the GV, MAP, and CVP remained at stable levels throughout the studies. In addition to increase the CVP, AS also decreased (P<0.05) the GV by 14%, 11.5%, and 16.5% in the 30, 50, and 70 microL groups, respectively. Vagotomy prevented the GV decrease. In contrast, the AS decreased (P<0.05) the GV by 21.3% in splanchnicectomized rats. SIGNIFICANCE: AS decreased the GV of rats in a volume-dependent manner, a phenomenon prevented by vagotomy but enhanced by celiac ganglionectomy.

Evaluation of gastrointestinal motility in awake rats: a learning exercise for undergraduate biomedical students.

Current medical curricula devote scarce time for practical activities on digestive physiology, despite frequent misconceptions about dyspepsia and dysmotility phenomena. Thus, we designed a hands-on activity followed by a small-group discussion on gut motility. Male awake rats were randomly submitted to insulin, control, or hypertonic protocols. Insulin and control rats were gavage fed with 5% glucose solution, whereas hypertonic-fed rats were gavage fed with 50% glucose solution. Insulin treatment was performed 30 min before a meal. All meals (1.5 ml) contained an equal mass of phenol red dye. After 10, 15, or 20 min of meal gavage, rats were euthanized. Each subset consisted of six to eight rats. Dye recovery in the stomach and proximal, middle, and distal small intestine was measured by spectrophotometry, a safe and reliable method that can be performed by minimally trained students. In a separate group of rats, we used the same protocols except that the test meal contained (99m)Tc as a marker. Compared with control, the hypertonic meal delayed gastric emptying and gastrointestinal transit, whereas insulinic hypoglycemia accelerated them. The session helped engage our undergraduate students in observing and analyzing gut motor behavior. In conclusion, the fractional dye retention test can be used as a teaching tool to strengthen the understanding of basic physiopathological features of gastrointestinal motility.

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.

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 microg/kg (5 doses, N = 10), 100 microg/kg (2, 3, 4 and 5 doses, N = 49) or 150 microg/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 microg/kg significantly decreased GE by 31-59% and GI transit by 55-93%. The effect of 5 doses of vincristine (150 microg/kg) on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 microg/kg). Fecal output decreased up to 48 h after the fifth dose of vincristine (150 microg/kg). Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 microg/kg or after 3-5 doses of 150 microg/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.

Acute intracranial hypertension increases gastric tonus in anesthetized rats.

We studied the acute effect of intracranial hypertension (ICH) on gastric tonus of anesthetized rats. Brain ventricles were cannulated bilaterally for intracerebro-ventricular pressure (ICP) monitoring and ICH induction. Next, a balloon catheter was inserted at the proximal stomach and coupled to a barostat for gastric volume (GV) monitoring by plethysmography. Arterial pressure (AP) and heart rate (HR) were monitored continuously during 80-min. After a 20-min basal period, they were submitted to control or ICH protocols. In controls, the ICP varied spontaneously up to the end. Other rats were subjected to ICP rising to 10, 20, 40 or 60 mmHg and kept at these levels for 30-min. Another group was subjected after basal period to stepwise ICH (ICP rising to 20, 40 and 60 mmHg at every 10-min interval). Next, the ICH rats were monitored for further 30-min. Other rats, previously submitted to a subdiaphragmatic vagotomy, splanchnicectomy plus ganglionectomy or their respective sham surgery, were also studied under ICH. Each subset consisted of 5-6 rats. Data were compared to respective basal values after ANOVA and Bonferroni's test. In controls, the GV, AP, HR values remained within stable levels. Besides inducing bradycardia and arterial hypertension, ICH10 mmHg decreased GV by 14.8% at the 50-min interval. In ICH20, 40 and 60 mmHg subsets, GV decreased 14.0, 24.5 and 30.6% at the 40-min interval, respectively. In stepwise ICH rats, GV decreased 10.2% and 12.7%, respectively under ICP of 40 and 60 mmHg. The GV values remained significantly lower than basal levels during the last 30-min of monitoring. Thus, ICH decreases the GV in an ICP-dependent pattern besides inducing Cushing's reflex.

A new model of autonomic dysreflexia induced by gastric distension in the spinal cord-transected rat.

Upper gastrointestinal (GI) motility inhibition after spinal cord injury has been classically considered to result from autonomic dysreflexia (AD). Animal models have been designed in rats to evaluate the presence of AD induced by colonic or bladder distension. However, there are no animal models of AD induced by gastric distension (GD). We examined whether controlled GD could induce AD and compared the pattern of hemodynamic responses induced by GD with colonic distensions (CD) and the interaction between them. Male Wistar rats underwent spinal cord transections performed at the level of C(7)-T(1), T(4)-T(5) and T(9)-T(10) (control) vertebrae and the presence of AD was evaluated after 1 day. In animals with C(7)-T(1) lesions, each CD in a series of 4 consecutive CDs triggered AD while GD only triggered AD after the 2 initial distensions in a series of 4 consecutive GDs. In animals with T(4)-T(5) lesions, in a protocol of 4 consecutive CDs or GDs, AD was triggered only by the 2 initial distensions. In 2 other protocols, consisting of 2 consecutive CDs or GDs followed respectively by 2 GDs or CDs, the effect of 2 GDs was attenuated in animals with C(7)-T(1) and T(4)-T(5) lesions but the hemodynamic changes induced by CDs were not affected by prior GDs. In summary, this is a new model of AD triggered by GD in rats. AD is more intense in animals with C(7)-T(1) lesions than after T(4)-T(5) lesions and AD triggered by GD can be attenuated by prior CDs.

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.

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% (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.

Peripheral neuropathy and neurological disorders in an unselected Brazilian population-based cohort of IBD patients.

BACKGROUND: Several neurological disorders have been described in inflammatory bowel disease (IBD) patients, but their exact frequency is unknown. METHODS: We prospectively studied the prevalence of neurological disorders (especially peripheral neuropathy) in a group of 82 patients with Crohn's disease (CD, n = 31) or ulcerative colitis (UC, n = 51) from 2 Brazilian tertiary care university clinics and followed them through a period of at least 1 year. All patients were interviewed and had complete neurological evaluations. RESULTS: Large-fiber sensory or sensorimotor polyneuropathy (PN) was observed in 16.1% of the CD and 19.6% of the UC patients. PN was usually mild, predominantly symmetric, and distal with axonal involvement. One patient had demyelinating PN at the diagnosis of CD. Mild carpal tunnel syndrome was common in female UC patients. Sensory symptoms without electromyography abnormalities, suggestive of small-fiber neuropathy or subclinical myelopathy, affected 29% and 11.8%, respectively. After excluding other known etiological or contributory factors for PN, 13.4% of the IBD patients had otherwise unexplained large-fiber or small-fiber PN (7.3% with large-fiber SM PN). Nondebilitating headache was the most common neurological complaint. Three patients had ischemic strokes, 5 were epileptic, and 1 transient chorea. CONCLUSIONS: Neurological disorders, especially PN, are common in our Brazilian cohort of IBD patients. They are diverse, multifactorial, and more common in women. Despite the mild phenotype in most cases, attention should be given by the general practitioner and gastroenterologist since they are frequently undiagnosed. Further studies are necessary to confirm these findings in populations with different genetic and nutritional backgrounds.

Haemodynamic changes after spinal cord transection are anaesthetic agent dependent.

1 To evaluate the effect of high spinal cord transection (SCT), between T4 and T5, on the mean arterial pressure (MAP) and heart rate in animals anaesthetized with different anaesthetic agents: ether (n = 12), 20% urethane, 1.2 g kg(-1) (n = 12), 2% tri-bromide-ethanol, 200 mg kg(-1) (n = 12); chloral hydrate and urethane, 75 and 525 mg kg(-1) respectively (n = 12). 2 In the animals anaesthetized with ether or urethane, SCT caused an immediate major drop in MAP, with hypotension and bradycardia throughout the next 10 min. In the animals anaesthetized with urethane + chloralose or tri-bromide-ethanol, SCT transiently increased MAP with subsequent hypotension and bradycardia. 3 In summary, the haemodynamic changes after complete, high SCT are anaesthetic agent dependent. Further research about the exact mechanisms responsible for these diverse autonomic changes is warranted.

Cardiovascular control after spinal cord injury.

Spinal cord injury (SCI) leads to profound haemodynamic changes. Constant outflows from the central autonomic pattern generators modulate the activity of the spinal sympathetic neurons. Sudden loss of communication between these centers and the sympathetic neurons in the intermediolateral thoracic and lumbar spinal cord leads to spinal shock. After high SCI, experimental data demonstrated a brief hypertensive peak followed by bradycardia with escape arrhythmias and marked hypotension. Total peripheral resistance and cardiac output decrease, while central venous pressure remains unchanged. The initial hypertensive peak is thought to result from direct sympathetic stimulation during SCI and its presence is anaesthetic agent dependent. Hypotension improves within days in most animal species because of reasons not totally understood, which may include synaptic reorganization or hyper responsiveness of alpha receptors. No convincing data has demonstrated that the deafferented spinal cord can generate significant basal sympathetic activity. However, with the spinal shock resolution, the deafferented spinal cord (in lesions above T6) will generate life-threatening hypertensive bouts with compensatory bradycardia, known as autonomic hyperreflexia (AH) after stimuli such as pain or bladder/colonic distension. AH results from the lack of supraspinal control of the sympathetic neurons and altered neurotransmission (e.g. glutamatergic) within the spinal cord. Despite significant progress in recent years, further research is necessary to fully understand the spectrum of haemodynamic changes after SCI.

Effect of preinjury large bowel emptying on the inhibition of upper gastrointestinal motility after spinal cord injury in rats.

Spinal cord transection (SCT) inhibits gastrointestinal motility in rats. We evaluated the effect of preinjury large bowel emptying on this phenomenon. Male Wistar rats (N = 52) were fasted for 24 or 48 hr with water ad libitum and pretreated with lactose (0.8 g) or saline. Next, laminectomy followed or not by complete SCT between T4 and T5 vertebrae was performed. Phenol red recovery in the stomach and proximal, medial, and distal small intestine was determined 1 day later. In animals submitted to 24 hr fasting + saline, SCT increased gastric recovery by 42.8% and decreased medial small intestine recovery by 56.2%, while 48 hr fasting + saline or 24 hr fasting + lactose prevented the inhibition of gastric emptying (GE) in SCT animals. The 48 hr fasting + lactose prevented the inhibition of both GE and gastrointestinal transit. SCT-induced inhibition of upper gastrointestinal motility may involve enhancement of inhibitory reflexes, which can be prevented by large bowel emptying.

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% (P<0.05). Hypovolemic rats (N = 12) were bled up to 10 ml/kg, a procedure that increased GV values by 15.8% (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.

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

Gastric emptying and gastrointestinal transit of liquid throughout the first month after thoracic spinal cord transection in awake rats.

Spinal cord transection (SCT) inhibits gastrointestinal motility in awake rats. We studied the gastric emptying (GE) and gastrointestinal transit of liquid throughout the first month after thoracic SCT. Male Wistar rats (N = 66) were submitted to laminectomy followed or not by complete SCT between T4 and T5 vertebrae. Phenol red recovery in the stomach, proximal, mid-and distal small intestine was determined 1, 7, 10, 15, and 30 days thereafter. Gastric recovery increased by 51.2 and 38.9% and mid-intestinal recovery decreased by 45.5 and 66.6% at one and seven days after SCT (P < 0.05). Proximal small intestine recovery increased by 45.9% 10 days after SCT but no inhibition of gastrointestinal motility was observed thereafter. Stool output significantly decreased in the first seven days after SCT (P < 0.05). In summary, gastrointestinal motility in awake rats is inhibited throughout the first 10 days after thoracic SCT but not thereafter.

Neural mechanisms involved in the delay of gastric emptying and gastrointestinal transit of liquid after thoracic spinal cord transection in awake rats.

Spinal cord transection (SCT) delays gastric emptying (GE), and intestinal and gastrointestinal (GI) transit of liquid in awake rats. This study evaluates the neural mechanisms involved in this phenomenon. Male Wistar rats (N = 147) were fasted for 16 h and had the left jugular vein cannulated followed by laminectomy or laminectomy + complete SCT between T4 and T5 vertebrae. The next day, a test meal (1.5 ml of a phenol red solution, 0.5 mg/ml in 5% glucose) was administered by gavage feeding and 10 min later cervical dislocation was performed. Dye recovery in the stomach, and proximal, mid and distal small intestine was determined by spectrophotometry. SCT inhibited GE and GI transit since it increased gastric recovery by 71.3% and decreased mid small intestine recovery by 100% (P < 0.05). Subdiaphragmatic vagotomy, celiac ganglionectomy + section of the splanchnic nerves, i.v. hexamethonium (20 mg/kg) or yohimbine (3 mg/kg) prevented the development of the SCT effect on GE and GI transit. Pretreatment with i.v. naloxone (2 mg/kg), L-NAME (3 mg/kg) or propranolol (2 mg/kg) was ineffective. Bilateral adrenalectomy or guanethidine (10 mg/kg) increased the magnitude of the GE inhibition, while i.v. prazosin (1 mg/kg) or atropine (0.5 mg/kg) decreased the magnitude but did not abolish the GE inhibition. In summary, the inhibition of GI motility observed 1 day after thoracic SCT in awake rats seems to involve vagal and possibly splanchnic pathways.

A plethysmometric method for gastric compliance studies in anesthetized rats.

A new method to study gastric volume by plethysmography is presented. Twenty male Wistar rats (250-300 g) were fasted for 24 h. After anesthesia with urethane (1.2 g/kg, i.p.), a tracheostomy was performed, and cervical vessels were cannulated. A balloon catheter was introduced per os and positioned in the proximal stomach. The opposite end of the catheter was connected to a reservoir (volume = 30 ml; inside diameter = 2.5 cm), coupled to a plethysmometer. A standard ionic solution was used to fill the balloon ( approximately 3.0 ml) and the communicating vessel system. Calibration experiments (n = 5) displayed a strong (r(2) = 0.99) correlation between graded balloon-volume changes and plethysmometric recordings. Because distending pressure of the stomach remained constant, the balloon-volume recordings were taken as gastric compliance index. Gastric volume changes, mean arterial pressure, and heart rate of animals of control and experimental groups were monitored for 90 min. The data were analyzed by analysis of variance and the Student-Newman-Keuls test. In control animals (n = 5), no significant changes on gastric volume and hemodynamic values were found. Experimental animals were treated with either yohimbine (n = 5) or bethanechol (n = 5) i.v. injections. The rats received consecutive doses of yohimbine (0.5 and 1 mg/kg) or bethanechol (1.5 and 3 microg/kg), 30 min apart. Both doses of each treatment transiently induced hypotension and bradycardia (p < 0.05). Yohimbine treatment (1 mg/kg) increased gastric volume by half (p < 0.05), whereas bethanechol (3 microg/kg) decreased it by 35% (p < 0.05). In summary, this work shows a suitable method to directly assess gastric compliance in anesthetized rats.

Complete cervical or thoracic spinal cord transections delay gastric emptying and gastrointestinal transit of liquid in awake rats.

STUDY DESIGN: To determine the changes on gastric emptying and gastrointestinal transit of liquid throughout the first week after spinal cord transection (SCT) in rats. METHODS: Male Wistar rats (n=121) were fasted for 16 h and a complete SCT or laminectomy was performed between C7 and T1 (cervical group) or between T4 and T5 (thoracic group). Dye recovery in the stomach, proximal, mid and distal small intestine was determined 30 min, 6 h, 1, 3 or 7 days after surgery. The test meal (1.5 ml of a phenol red solution, 0.5 mg/ml in 5% glucose) was intragastrically administered and the animals sacrificed by cervical dislocation 10 min later. RESULTS: Cervical SCT increased dye recovery in the stomach (P<0.05) by 70.1, 78.7, 34.2, 41.3 and 50.9% while it decreased recovery in the mid small intestine (P<0.05) by 87.1, 85.1, 74.8, 59.5 and 80.1%, respectively 30 min, 6 h, 1, 3 and 7 days after SCT. Thoracic SCT increased gastric recovery (P<0.05) by 43.5, 67.6, 51.2, 75.4 and 38. 9% while it decreased recovery in the mid small intestine (P<0.05) by 100, 100, 45.6, 100 and 66.6%, respectively 30 min, 6 h, 1, 3 and 7 days after SCT. A separate group was submitted to laminectomy+bilateral sciatic nerve transection (paraplegic sham). Gastric emptying and gastrointestinal transit were not inhibited in this group. CONCLUSION: In summary, gastric emptying and gastrointestinal transit of liquid are inhibited throughout the first week after high SCT in awake rats.

Neural mechanisms involved in the delay of gastric emptying of liquid elicited by acute blood volume expansion in awake rats.

We have previously reported that acute blood volume expansion in awake rats delays the gastric emptying of a liquid meal, using the phenol red method. In this study we attempted to investigate the neural mechanisms involved in this phenomenon. Blood volume expansion, due to Ringer-bicarbonate infusion up to a volume equivalent to 5% of body weight, decreased the gastric emptying of a liquid meal by half (38.2 +/- 1.8 vs 18.7 +/- 3.2%, P < 0.05). The blood volume expansion effect on gastric emptying of liquid was prevented by separate pretreatments, consisting of subdiaphragmatic vagotomy or i.v. injection of hexamethonium (20 mg kg-1) or yohimbine (3 mg kg-1). Intravenous injection of atropine (0.5 mg kg-1), guanethidine (10 mg kg-1), L-NAME (3 mg kg-1), prazosin (1 mg kg-1) or propranolol (2 mg kg-1) did not prevent the blood volume expansion effect on gastric emptying. Bilateral adrenalectomy or coeliac ganglionectomy were also ineffective. The results indicate that blood volume expansion decreases gastric emptying of liquid through vagal-dependent pathways, sensitive to hexamethonium and yohimbine. Evidence for the participation of the peripheral sympathetic nervous system was not found.