Sarr, M. G.

The neurotransmitter(s) that generates the fast component of the inhibitory junction potential (IJP-F) in human jejunal circular smooth muscle is not known. The aim of this study was to determine the role of ATP and purinergic receptors in the generation of the IJP-F in human jejunal circular smooth muscle strips. The P2-receptor antagonist suramin (100 μM) reduced the IJP-F by 28%. Apamin (1 μM) reduced the IJP-F by 25%. Desensitization of muscle strips with the putative P2x-receptor agonist α,β-methylene ATP (α,β-MeATP, 100 μM) decreased the IJP-F by 44%, and desensitization with the putative P2y-receptor agonist adenosine 5′- O-2-thiodiphosphate (ADPβS) completely abolished the IJP-F. Desensitization with the putative P2y-receptor agonist 2-methylthioATP had no effect on the IJP-F. Exogenous ATP evoked a hyperpolarization with a time course that matched the IJP-F. The ATP-evoked hyperpolarization was reduced by apamin and suramin, reduced by desensitization with α,β-MeATP (69% decrease), and abolished by desensitization with ADPβS. These data suggest that the IJP-F in human jejunal circular smooth muscle is mediated in part by ATP through an ADPβS-sensitive P2receptor.

We have previously described a negative feedback loop that inhibits duodenal motility when nutrients are infused into the ileum and colon. In the present study, we examined the role of extrinsic innervation and plasma levels of peptide YY (PYY) in mediating this phenomenon. We perfused neurally intact ( n = 5 dogs) or extrinsically denervated ( n = 6 dogs) isolated loops of proximal colon with isomolar NaCl or a mixed-nutrient solution at 2 and 6 ml/min for 4 h during fasting or for 2 h beginning 15 min after a meal. Both rates of infusion with NaCl prolonged the cycle length of the duodenal migrating motor complex (MMC) in the group with neurally intact loops but not in the group with extrinsically denervated loops. Nutrient infusions increased the MMC cycle length in both groups. Integrated plasma concentrations of PYY were increased by nutrients but not by NaCl in both groups. These data suggest that increased volumes and unabsorbed nutrients in the proximal colon alter proximal small bowel motility. Volume-induced effects are mediated via extrinsic nerves, whereas nutrient-induced effects may be mediated by humoral factors, such as plasma PYY.

Motilin is a potent agonist for gastrointestinal smooth muscle contraction and has been proposed to regulate the onset of phase III of the migrating motor complex in dogs and humans. The effects of motilin and OHM-11526, a motilin antagonist in rabbit smooth muscle strips, were examined in isolated canine and human jejunal circular smooth muscle cells using whole cell patch-clamp techniques with Ba2+ as the charge carrier. Effects of both drugs on inward current through L-type Ca2+ channels (ICaL) in both canine and human cells were first observed at 10(-3) M. At 10(-6) M, motilin increased ICaL in canine and human jejunal circular smooth muscle cells by 43 +/- 20 and 45 +/- 11%, respectively, and OHM-11526 increased ICaL by 54 +/- 8 and 54 +/- 14%, respectively. The increase in inward current was blocked by nifedipine and by guanosine 5'-O-(2-thiodiphosphate) but not by pertussis toxin. Washout of both drugs resulted in a further increase in ICaL. These data suggest that both motilin and OHM-11526 activate and ICaL in human and canine jejunal circular smooth muscle cells through a G protein-coupled mechanism.

The aim of this study was to determine what factors influence the direction of movement of canine jejunal chyme. In four dogs, pacing electrodes were implanted near each end of a 50-cm jejunal Vella loop, while recording electrodes and intraluminal pressure catheters were spaced along the loop. After recovery, the loop was perfused from either the proximal stoma (forward flow) or the distal stoma (reversed flow), and effluent was collected from the nonperfused stoma. The pacesetter potentials were paced electrically in a forward (aborad) or a reverse (orad) direction. During control conditions (forward flow-forward pacing), the mean transit time of liquids was 2.6 +/- 0.1 min (mean +/- SE) and the static volume of the loop was 8.8 +/- 0.3 ml. Reversing both direction of flow and direction of pacesetter potential propagation slowed transit (4.4 +/- 0.4 min; P less than 0.05) and increased loop volume (16.0 +/- 1.0 ml; P less than 0.01). Reversing flow with forward pacing resulted in even slower transit (7.5 +/- 1.2 min; P less than 0.05), maintained a large volume (33 +/- 10 ml), and increased basal pressure in the loop from -1.2 +/- 1.7 (control) to 2.3 +/- 1.6 mmHg (P less than 0.05). These observations suggest that the direction of propagation of jejunal pacesetter potentials influences the direction of movement of jejunal chyme but that other factors have a role as well.

Our hypothesis was that the direction of liquid transit through the canine jejunum is determined by the direction that single jejunal pressure waves spread, while the direction of solid transit depends on the direction of spread of both single waves and clustered waves. In six dogs, 80-cm jejunal Vella loops were made and fitted with manometric catheters and serosal electrodes. After recovery, transit of liquids (Ringer lactate) and solids (2.4-mm nylon spheres) placed into the center of the loop was determined in the conscious animals while pacing the loop in a forward direction or in a backward direction. Under fasting and fed conditions, single pressure waves followed the direction of pacing, while the direction of migration of clustered waves was not determined by the direction of pacing. Liquid transit always followed the direction of single pressure waves. In contrast, solids moved distally regardless of the direction of pacing, except when liquids were also present in the lumen, in which case solids moved in the same direction as the single pressure waves.

Thirty-eight cells, freshly isolated from circular smooth muscle of normal human jejunum obtained from nine patients undergoing weight-reduction surgery for morbid obesity, were patch clamped using a perforated patch-clamp technique. A highly potassium-selective voltage-dependent outward current was present in all cells. The current was carried by a 220-pS channel that activated near -75 mV and reached unit open probability at about +10 mV. Blockade of the current by quinidine (50 microM) and tetraethylammonium (25 mM) was accompanied by membrane depolarization to 0 to -3 mV, suggesting that this current was the major determinant of the membrane potential. Flufenamic and mefenamic acid at concentrations comparable with blood levels reached when these drugs are used in clinical therapy as nonsteroidal anti-inflammatory agents, activated the potassium outward current and hyperpolarized the membrane potential. The shift in the membrane potential for 250 microM flufenamic acid was -36 +/- 24 (SD) mV. Activation was rapid (seconds) and reversible. It was concluded that normal human jejunal circular smooth muscle cells have a highly potassium-selective outward current, which is the major determinant of the membrane potential and which is activated by fenamates.

Abstract We reviewed our recent experience with management of 23 consecutive patients with acute necrotizing pancreatitis. All patients had documented necrotizing pancreatitis with parenchymal or peripancreatic necrosis. Our method of treatment has evolved from our previous approach of controlled open lesser sac drainage (marsupialization) to staged necrosectomy I debridement with delayed primary closure over drains. With this latter approach, hospital mortality was 4 of 23 patients (17 per cent), but significant morbidity still occurred in 12 of 23 patients (52 per cent). However, recurrent intra-abdominal abscess before discharge occurred in only one patient. We believe that this operative approach toward the severely ill patient with acute necrotizing pancreatitis who requires operative intervention will minimize the occurrence of intra-abdominal sepsis.

Abstract Background Long-term functional outcome after operative treatment of necrotizing pancreatitis (NP) has not been studied extensively. Methods Pancreatic function, performance status, recurrence of symptoms and other related problems were analysed in 44 consecutive patients successfully discharged from hospital after operative necrosectomy (1983–1995) and followed up completely for a mean of 5 years. Results Clinical pancreatic insufficiency developed in half the patients. Diabetes mellitus (11 patients), steatorrhoea (six) or both (five) were associated with a mean estimate of 52, 66 and 67 per cent parenchymal necrosis respectively. Normal pancreatic function was associated with 27 per cent parenchymal necrosis (P < 0·05). Diabetes worsened while steatorrhoea tended to improve over time. Abdominal pain and pancreatitis recurred in six and two patients respectively. Performance status worsened in four patients because of recurrent pancreatitis and severe steatorrhoea. Poor long-term performance was associated with a higher Acute Physiology And Chronic Health Evaluation II score on admission (mean 14 versus 9). Conclusion NP has prominent effects on long-term pancreatic exocrine and endocrine function in half the patients, but most preserve a good overall functional status. The development of pancreatic insufficiency varies with the extent of pancreatic parenchymal necrosis.