Vascularised fatty tissue: its role in prevention of the symptoms of Frey syndrome after parotidectomy.

We studied 37 consecutive patients who had parotidectomies between 2008 and 2017 and who had vascular fat flaps inserted to replace the excised parotid tissue and prevent Frey syndrome. They were followed up for 1-9 years to check for the relevant symptoms. We studied 17 female and 20 male patients, mean age 52 (range 19-78) years. The flaps took a maximum of 17minutes to dissect. There was no donor site morbidity, the vascular fat flap was stable in all cases for up to nine years, and none of the patients complained of symptoms of Frey syndrome.

COX inhibition excites enteric nerves that affect motility, alkaline secretion, and permeability in rat duodenum.

In anesthetized rats, the cyclooxygenase (COX) inhibitor indomethacin induces duodenal motility, increases duodenal mucosal alkaline secretion (DMAS), and evokes a transient increase in duodenal paracellular permeability (DPP). To examine whether enteric nerves influence these responses, the duodenum was perfused with lidocaine. Motility was assessed by measuring intraluminal pressure, and DPP was determined as blood-to-lumen clearance of (51)Cr-EDTA. DMAS was assessed by titration. In control animals, few contractions occurred during saline perfusion and lidocaine did not alter this condition. Perfusion with 0.03-0.1% lidocaine did not affect DMAS or DPP whereas 0.3-1% lidocaine reduced DMAS and increased DPP. Indomethacin induced motility and doubled DMAS. Application of 0.03% lidocaine on the duodenal serosa reduced motility and DMAS whereas 0.03% lidocaine applied luminally inhibited DMAS only. Higher concentrations of lidocaine abolished the increase in DMAS and changed the motility pattern to numerous low-amplitude contractions, the latter effect being blocked by iloprost. The lidocaine-induced increases in DPP were markedly higher than in controls. We conclude that indomethacin activates enteric nerves that induce motility, increase DMAS, and decrease DPP.

Enhanced intestinal motility influences absorption in anaesthetized rat.

The subject of this investigation was to study influence of the intestinal motility on absorption of 3-o-methyl-D-glucose (3-OMG), mannitol and polyethylene glycol (PEG 4000), used as absorption route markers, while monitoring cardiovascular parameters in an intestinal in situ model in rats. Rats were anaesthetized with Inactin(R) and Rapinovet(R). A segment of duodenum, approximately 10 cm, was perfused single-pass with saline containing unlabelled and radioactive 3-OMG, PEG 4000 or mannitol. The PEG 4000 was recovered almost completely in the intestinal perfusate suggesting an intact mucosal integrity. Most animals exhibited an intestinal contractile activity resembling fed motility except seven out of 19 given Rapinovet, which showed a 'burst-type' pattern resembling migrating motor complex (MMC). Absorption of 3-OMG in rats with MMC-like motility appears to be lower than in rats with fed-like motility, while no such difference was seen for mannitol. Moreover, there was a positive correlation (r 2=0.75) between intestinal activity (fed) and absorption of 3-OMG, but not with absorption of mannitol. The carrier-mediated absorption of 3-OMG was not only influenced by intestinal motility, but also by its pattern. This was not observed with mannitol, which is passively absorbed.

The role of P-glycoprotein in limiting intestinal regional absorption of digoxin in rats.

The objective of this work was to study the role of regional intestinal efflux activity of P-glycoprotein (Pgp) in situ in anesthetized rats in limiting the absorption of digoxin. A 10-cm portion of duodenum or jejunum, or 5-cm of colon was perfused single-pass with saline containing [(3)H]digoxin while the appearance of radioactivity in the blood was measured. Verapamil in the perfusate was used as a modulator of Pgp in the intestinal mucosa. Net water absorption, mucosal integrity, and intestinal motility of the isolated segment were monitored, as well as heart rate and blood pressure. Excretion of i.v. administered unlabelled digoxin, 1 mg/kg, into the intestine while perfusing the duodenum-proximal jejunum region, was studied for comparison. At a perfusate concentration of 1 mM, verapamil caused a dramatic increase in [(3)H]digoxin absorption rate from duodenum and jejunum, while the effect in colon was insignificant. At concentrations of 0.1, 1, and 2.5 mM in the duodenal perfusate, verapamil increased the absorption rate of [(3)H]digoxin in a dose-dependent manner. The lowest concentration almost doubled the rate without having any significant effects on the cardiovascular system, intestinal motility, or net absorption of water. The excretion rate of unlabelled digoxin from the blood into the gut lumen was found to be halved in the presence of 0.5 mM verapamil in the perfusate. Absorption rate of [(3)H]digoxin in the rat is likely limited by Pgp-mediated efflux. The data indicate that Pgp plays an important role for digoxin efflux in the small intestine only.

Interaction between prostanoids, NO, and VIP in modulation of duodenal alkaline secretion and motility.

The relation between duodenal motility and duodenal mucosal alkaline secretion (DMAS) was examined in anesthetized rats. The duodenum was perfused with saline, and DMAS was determined by titration. Duodenal motility, assessed by intraluminal pressure measurements, was induced by indomethacin and/or N omega-nitro-L-arginine methyl ester (L-NAME) and inhibited by iloprost or vasoactive intestinal peptide (VIP). Six of 66 rats showed spontaneous duodenal contractions. Basal DMAS was higher in these rats than in those without contractions. Rats treated with indomethacin and L-NAME before abdominal operation exhibited duodenal motility postoperatively and had higher DMAS than in controls. Iloprost abolished both the duodenal motility increase and increase in DMAS induced by indomethacin. L-NAME-induced motility and increase in DMAS were antagonized by L-arginine. VIP increased DMAS without affecting motility. VIP abolished indomethacin-induced motility and augmented indomethacin-stimulated DMAS. VIP reduced L-NAME-induced motility and slightly increased L-NAME-stimulated DMAS. It is concluded that DMAS varies with duodenal motility. Prostaglandins and NO inhibit duodenal motility, thereby indirectly reducing DMAS. VIP may have dual effects on DMAS, an inhibitory action mediated via smooth muscle relaxation and a stimulatory action independent of motility.

Comparative study of the effects of nitric oxide synthase and cyclo-oxygenase inhibition on duodenal functions in rats anaesthetized with inactin, urethane or alpha-chloralose.

This study was undertaken to investigate the effects of a cyclo-oxygenase and a nitric oxide synthase (NOS) inhibitor on duodenal mucosal alkaline secretion (DMAS), motility and mucosal permeability in inactin-, urethane- and alpha-chloralose anaesthetized rats. Proximal duodenum was perfused with a 150 mM NaCl solution and DMAS was determined by back titration. Mucosal permeability was assessed by measuring blood to lumen clearance of 51Cr-EDTA and duodenal motility by measuring intraluminal pressure. Mean arterial blood pressure and mucosal permeability were significantly lower in urethane- than in inactin- or alpha-chloralose anaesthetized rats (urethane: 90 +/- 2 mm Hg and 0.15 +/- 0.02 mL min-1 100 g-1; inactin: 112 +/- 5 mm Hg and 0.62 +/- 0.15 mL min-1 100 g-1; alpha-chloralose: 111 +/- 4 mm Hg and 0.61 +/- 0.06 mL min-1 100 g-1, respectively). Basal (pre-drug) DMAS was significantly lower in urethane rats (6.2 +/- 1.0 mumol cm-1 h-1) than in alpha-chloralose (9.3 +/- 1.2 mumol cm-1 h-1), but not different from that in inactin-anaesthetized rats (7.5 +/- 0.8 mumol cm-1 h-1). No or very few spontaneous duodenal contractions occurred under the control (pre-drug) conditions in any group. All animals responded to the cyclo-oxygenase inhibitor indomethacin or the NOS inhibitor N-nitro-L-arginine-methyl-ester (L-NAME) with induction of duodenal motility and an increase in DMAS. The effect of indomethacin or L-NAME on mucosal permeability was similar in all anaesthetic groups except that L-NAME induced a transient increase in the inactin and alpha-chloralose groups but a sustained increase in urethane-anaesthetized animals. It is concluded that inactin- and alpha-chloralose anaesthetized rats do not differ regarding the studied basal values. Urethane-anaesthetized animals differed from rats given the other two anaesthetics in that basal mucosal permeability and mean arterial blood pressure were lower. Endogenous prostaglandins and NO contribute to the postoperative ileus and the low rate of DMAS also in urethane- and alpha-chloralose.

Mucus and alkali secretion in the rat duodenum: effects of indomethacin, N omega-nitro-L-arginine, and luminal acid.

BACKGROUND & AIMS: Duodenal mucus and bicarbonate secretion appear to play an essential role in the protection of the duodenum. The aim of this study was to examine duodenal bicarbonate and mucus secretion and the effects of cyclooxygenase inhibition, nitric oxide synthase inhibition, and luminal acid. METHODS: Duodenal mucus gel thickness was measured using microelectrodes during intravital microscopy in anesthetized rats. Bicarbonate secretion was measured using back-titration. RESULTS: A continuous layer of mucus with a mean thickness of 284 +/- 11 microns (n = 35) and a mean alkaline secretion of 0.18 +/- 0.01 mumol.cm-2.min-1 were found in untreated animals. Indomethacin decreased both mucus and bicarbonate secretion by about 35%. NO synthase inhibition with N omega-nitro-L-arginine reduced mucus secretion by about 21% but increased bicarbonate secretion by 39%. Exposure of the mucosal surface to 10 mmol/L HCI increased mucus secretion by 44% and bicarbonate secretion by 22%. CONCLUSIONS: The duodenal mucus layer is continuous. It can be easily removed, and new secretion can be followed. Duodenal mucus secretion is strongly stimulated by luminal acid and endogenous prostanoids and less markedly by NO, whereas bicarbonate secretion is stimulated by acid and endogenous prostanoids and inhibited by endogenous NO.

Effects of nitric oxide inhibition on duodenal function in rat: involvement of neural mechanisms.

This study examines the integrative response of several duodenal functions to nitric oxide synthase inhibition. Effects of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) were studied in anesthetized rats, using in situ duodenal perfusion. L-NAME increased bicarbonate secretion, permeability, and fluid secretion and induced motility. Injection of L-arginine abolished L-NAME-induced motility and lowered the secretion of bicarbonate and fluid. Pretreatment with the nicotinic receptor antagonist hexamethonium prevented the rise in bicarbonate secretion and motility in response to L-NAME but did not affect the increase in mucosal permeability. Atropine diminished the L-NAME-induced increases in permeability, motility, and fluid secretion. The adrenolytic drug guanethidine did not alter the responses to the inhibitor. These results suggest that nitric oxide inhibits duodenal motility and bicarbonate secretion by suppressing a stimulatory, nicotinic receptor-dependent, neural mechanism. The L-NAME-induced contractions involve both a cholinergic, atropine-sensitive pathway and nonadrenergic, noncholinergic neural transmission. Muscarinic receptors also mediate part of the L-NAME-induced increases in mucosal permeability and fluid secretion.

Villus tip microcirculation in the rat duodenum.

Duodenal microvascular perfusion was measured in anaesthetized rats both as erythrocyte velocity (rcv) in capillaries in the tip of duodenal villi and by laser-Doppler flowmetry (LDF). Rcv increased transiently by about 40% during the first 5 min of luminal exposure to 10 mM (NaCl to isotonicity) hydrochloric acid, while LDF measurements only showed a transient increase of about 7%, followed by a prolonged reduction by about 11%. Since the LDF signal is a measure not only of villus microcirculation but also of blood flow in the deeper layers, our results may suggest that blood flow is transiently redistributed towards the villi from deeper layers. Hypovolaemia (bleeding by approximately 10% of the blood volume) reduced rcv in the capillaries by 63% during the first 5 min of hypotension, but reduced LDF only by about 12%, a discrepancy which suggests a shift in blood flow from the tip to deeper layers. The experiments were performed under atmospheric oxygen tension, but rcv in the villus capillaries exposed to abdominal PO2 (approximately 45 mmHg) did not differ significantly from the values obtained under the atmospheric oxygen condition, either in the resting situation or during hypotension. In conclusion, we have developed an animal model in which red cell velocity in the tip of the duodenal villi can be studied for several hours and in which alkaline secretion from the duodenum is similar to previously reported levels. Our results show that the villus tip microcirculation in the duodenum may respond differently from that of deeper layers of the duodenal wall.

Prostaglandins reduce hydrochloric acid-induced increase in duodenal mucosal permeability by a mechanism not related to stimulation of alkaline secretion.

The aim was to investigate whether prostaglandins affect HCl-induced mucosal permeability and to elucidate the role of mucosal bicarbonate secretion in protection. Proximal duodenum of anaesthetized rats were perfused with hydrochloric acid and the effects on luminal alkalinization, mucosal permeability and morphology examined in the absence and in the presence of prostaglandin E2 and/or indomethacin. Luminal alkalinization was determined by back titration of the perfusate and mucosal permeability assessed by measuring the clearance of 51Cr-labelled ethylenediaminetetraacetat ([51Cr]EDTA) from blood-to-intestinal lumen. Perfusion with 100 mM HCl for 5 min increased mucosal permeability sixfold and caused villus tip damage. Luminal administration of PGE2 at a concentration of 10(-6) M had no effect whereas 10(-4) M increased alkalinization by 100% but neither concentration affected the HCl-induced increase in mucosal permeability. PGE2 (10(-4) M), however, improved the ability of the duodenal mucosa to recover from the HCl-induced increase in mucosal permeability. Indomethacin (5 mg kg-1, i.v.) increased alkalinization, augmented HCl-induced mucosal permeability and aggravated mucosal injury. In animals pre-treated with PGE2 plus indomethacin, the HCl-induced increases in mucosal permeability were lower and injury less pronounced than in animals treated with indomethacin alone. No correlation was found between the rate of alkalinization and the HCl-induced increase in mucosal permeability. It is concluded that endogenous prostaglandins reduced the extent of 100 mM HCl-induced duodenal mucosal damage by a mechanism other than the stimulation of alkaline secretion.

Elevation of intraluminal pressure and cyclooxygenase inhibitors increases duodenal alkaline secretion.

Our aim was to study the effects of intraluminal hydrostatic pressure on duodenal mucosal alkaline secretion (DMAS) and permeability in anesthetized rats. A segment of proximal duodenum was perfused with saline and the rate of DMAS determined by backtitration. Mucosal permeability was assessed by measuring the clearance of 51Cr-EDTA (ED-C1) from blood to lumen. Raising the intraluminal hydrostatic pressure 6 mmHg above basal for 40 min induced a 75% increase in DMAS and a transient increase in ED-C1. This stimulation of DMAS was not affected by pretreatment with the muscarinergic receptor antagonist atropine (0.5 mg/kg i.v.), or the opioid receptor antagonist naloxone (15 micrograms/kg i.v.) but was strongly reduced by stripping the nerves around the carotid arteries and abolished by the ganglion blocker hexamethonium (10 mg/kg i.v.). When the distension was prolonged to 90 min, the net increase in DMAS decreased with time, indicating an adaptive mechanism. The cyclooxygenase inhibitors indomethacin (5 mg/kg i.v.) and meclofenamate (5 mg/kg i.v.) induced intermittent elevations of intraluminal pressure and increased DMAS by > 100%. This was associated with a transient increase in ED-C1. Indomethacin increased DMAS in a dose-related fashion, and the rise in both intraluminal pressure and DMAS was abolished by hexamethonium but not affected by stripping the nerves around the carotid arteries. Elevation of intraluminal pressure did not augment the rise in DMAS induced by indomethacin. It is concluded that luminal distension and cyclooxygenase inhibition increase DMAS by a similar, but not identical, neural mechanism involving nicotinergic receptors. It is speculated that the indomethacin-induced rise in DMAS is mediated via induction of duodenal motility.

Characterization of 51Cr-EDTA as a marker of duodenal mucosal permeability.

Proximal duodenum was perfused with various solutions and mucosal permeability assessed by measuring the clearance of 51Cr labelled ethylenediaminetetra-acetate (EDTA) from blood-to-intestinal lumen in anaesthetized rats. Net flux of fluid was determined by measurement of effluent weight changes. Perfusion of duodenum with 50 mM NaCl significantly increased fluid absorption but had no effect on EDTA clearance. EDTA clearance was unaffected by perfusion with 400 mM or 800 mM mannitol. Perfusion with 400 mM NaCl induced a sustained fluid secretion and a small but irregular increase (40%) in EDTA clearance. A significant 3.6-fold increase in clearance was obtained in response to perfusion of duodenum with deionized water. Similarly, perfusion with either 20 mM HCl or 50 mM ethyleneglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA) significantly increased the EDTA clearance 3.3-fold and 2-fold respectively. Perfusion with a hypotonic HCl-solution (10 mM HCl + 40 mM NaCl) increased fluid absorption and the EDTA clearance. It is concluded that no positive linear relationship exists between luminal osmolality and 51Cr-EDTA movement across the mucosa. It is postulated that high luminal acidity or extreme hypotonicity increase the EDTA clearance by widening of and/or disruption of intercellular junctional structure.