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.

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.

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.

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.

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% glucose) to normovolemic control animals and to animals submitted to BV expansion (Ringer-bicarbonate, i.v. infusion, 1 ml/min, volume up to 5% body weight). BV expansion decreased GE and GI transit rates in SHAM laparotomized animals by 52 and 35.9% (P < 0.05). Fundectomy increased GE and GI transit rates by 61.1 and 67.7% (P < 0.05) and prevented the effect of expansion on GE but not on GI transit (13.9% reduction, P < 0.05). Pyloroplasty also increased GE and GI transit rates by 33.9 and 44.8% (P < 0.05) but did not prevent the effect of expansion on GE or GI transit (50.7 and 21.1% 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.

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 charcoal meal (2.5 ml of an aqueous suspension consisting of 5% charcoal and 5% 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 i.v. infusion of 1 ml/min Ringer bicarbonate in volumes of 3, 4 or 5% body weight delayed gastrointestinal transit at 10 min after test meal administration by 21.3-26.7% (P < 0.05), but no effect was observed after 1 or 2% body weight expansion. The effect of blood volume expansion (up to 5% 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.

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% glucose solution) was administered intragastrically (1.5 ml) and the animals were sacrificed by an i.v. 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%, 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%, 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%, 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%, 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.

Acute extracellular fluid volume changes increase ileocolonic resistance 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% NaCl, 20 ml/min, volume up to 5% body weight) and controlled hemorrhage (up to a 50% drop in mean arterial pressure). Mean ileocolonic flow (N = 6) was gradually and significantly decreased during the expansion (17.1%, P < 0.05) and expanded (44.9%, P < 0.05) periods while mean ileal flow (N = 7) was significantly decreased only during the expanded period (38%, P < 0.05). Mean colonic flow (N = 7) was decreased during expansion (12%, P < 0.05) but returned to control levels during the expanded period. Mean ileocolonic sphincter flow (N = 6) was not significantly modified. Mean ileocolonic flow (N = 10) was also decreased after hemorrhage (retracted period) by 17% (P < 0.05), but saline flow was not modified in the other separate circuits (N = 6, 5 and 4 for ileal, ileocolonic sphincter and colonic groups, respectively). The expansion effect was blocked by atropine (0.5 mg/kg, i.v.) 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.