Gastric Branches Research Articles

Identifying the Source of a Humoral Factor of Remote (Pre)Conditioning Cardioprotection.

Signalling pathways underlying the phenomenon of remote ischaemic preconditioning (RPc) cardioprotection are not completely understood. The existing evidence agrees that intact sensory innervation of the remote tissue/organ is required for the release into the systemic circulation of preconditioning factor(s) capable of protecting a transplanted or isolated heart. However, the source and molecular identities of these factors remain unknown. Since the efficacy of RPc cardioprotection is critically dependent upon vagal activity and muscarinic mechanisms, we hypothesized that the humoral RPc factor is produced by the internal organ(s), which receive rich parasympathetic innervation. In a rat model of myocardial ischaemia/reperfusion injury we determined the efficacy of limb RPc in establishing cardioprotection after denervation of various visceral organs by sectioning celiac, hepatic, anterior and posterior gastric branches of the vagus nerve. Electrical stimulation was applied to individually sectioned branches to determine whether enhanced vagal input to a particular target area is sufficient to establish cardioprotection. It was found that RPc cardioprotection is abolished in conditions of either total subdiaphragmatic vagotomy, gastric vagotomy or sectioning of the posterior gastric branch. The efficacy of RPc cardioprotection was preserved when hepatic, celiac or anterior gastric vagal branches were cut. In the absence of remote ischaemia/reperfusion, electrical stimulation of the posterior gastric branch reduced infarct size, mimicking the effect of RPc. These data suggest that the circulating factor (or factors) of RPc are produced and released into the systemic circulation by the visceral organ(s) innervated by the posterior gastric branch of the vagus nerve.

Rabbit hepatic arterial anatomy variations: implications on experimental design

The VX2 rabbit model of liver cancer is commonly used to evaluate the efficacy of locoregional anticancer therapy and knowledge of the hepatic arterial anatomy in the rabbit is important for catheter-directed experiments. To describe the normal anatomy and anatomic variations of the celiac axis and hepatic artery in the rabbit. Angiograms of 222 rabbits were retrospectively reviewed. The branching pattern of the celiac axis was classified and the diameters of the major branches were measured. Paired t-tests were used to compare the difference between the average sizes of arteries. Variant celiac axis or hepatic artery anatomy was noted in 25.9% of angiograms, with the gastric branches arising from the proper hepatic artery in 23.3% of cases. The celiac axis could be successfully classified into one of five distinct branching patterns in 193 (86.9%) cases. The mean diameters of the right and left hepatic arteries were 0.67 mm (95% CI [0.64, 0.7]) and 1.25 mm (95% CI [1.19, 1.31]), respectively. The mean diameters of the medial and lateral branches of the left hepatic artery were 0.63 mm (95% CI [0.6, 0.67]) and 0.91 mm (95% CI [0.86, 0.96]), respectively. The right hepatic artery was significantly smaller than the left hepatic artery and the lateral branch of the left hepatic artery (all P values <0.0001). Arterial variants in the rabbit are not uncommon. The proper hepatic artery often gives origin to gastric artery branches. To facilitate superselective intra-arterial intervention, the left lateral lobe of the liver should be targeted for tumor implantation because of the significant size difference between the right and left hepatic arteries.

TRH/TRH-R1 Receptor Signaling in the Brain Medulla as a Pathway of Vagally Mediated Gut Responses During the Cephalic Phase

Pavlov's seminal findings in the early twentieth century showed that the sight, smell or taste of food in dogs with chronic esophagostomy induces a vagal-dependent gastric acid secretion. These observations established the concept of the cephalic phase of digestion. Compelling experimental evidence in rats indicates that the three amino acid peptide thyrotropin-releasing hormone (TRH) expressed in the brainstem plays a key role in the vagal stimulation of gastric function. Neurons in the dorsal motor nucleus of the vagus (DMN) expressed TRH receptor subtype (TRH-R1) and received efferent input from TRH containing fibers arising from TRH synthesizing neurons in the raphe pallidus, raphe obscurus, and the parapyramidal regions. TRH microinjected into the DMN or intracisternally excites the firing of DMN neurons and stimulates efferent activity in the gastric branch of the vagus nerve and gastric myenteric cholinergic neurons. At the functional level, this results in a vagally-mediated and atropine-sensitive stimulation of gastric epithelial and endocrine cells secreting acid, pepsin, serotonin, histamine and ghrelin, and enteric neurons leading to increased gastric motility and emptying. Importantly, the blockade of TRH or TRH-R1 in the brainstem by pretreatment into the cisterna magna or the DMN with TRH antibody or TRH-R1 oligodeoxynucleotide antisense respectively abolishes the stimulation of gastric acid induced by sham-feeding. The gastric response to TRH injected into the DMN is potentiated by serotonin and the proTRH flanking peptide, Ps4 and suppressed by a number of brainstem peptides and cytokines activated during stress or immune response and inhibiting food intake and gastric acid secretion. These convergent data strongly support a physiological involvement of TRH signaling pathway in the brainstem to stimulate vagal activity and identified TRH-TRH-R1 system as a major effector in the dorsal vagal complex to drive the vagally mediated gut response triggered by the cephalic phase.

Histopathological evidence of invasive gastric mucormycosis after transarterial chemoembolization and liver transplantation

We describe a case of a 62-year-old diabetic woman with hepatocellular carcinoma due to chronic hepatitis B virus infection. Two weeks after orthotopic liver transplantation, endoscopy for massive upper gastrointestinal bleeding revealed a large necrotic area in the gastric fundus. The patient underwent emergency resection. Histopathologically, angioinvasive mold infection compatible with mucormycosis was diagnosed in a large area of necrosis, mimicking an atypically localized gastric ulcer. Foreign bodies originating from transarterial chemoembolization (TACE) performed 7 and 8 months earlier and 40 days before transplantation were identified in the submucosal tissue. The patient was treated with liposomal amphotericin B (LAB) for 5 weeks, followed by 7 weeks of posaconazole. Follow-up biopsies after 1 and 5 months confirmed successful treatment. Review of the radiological images of the TACE procedure showed that some of the TACE material had been diverted to the stomach via an accessory gastric branch originating from the left hepatic artery. TACE agents may be associated with chronic, refractory gastroduodenal ulcers. We hypothesize that the ischemic lesion was first colonized with presumed Mucorales mold and invasive growth was promoted by the posttransplantation immunosuppression. Careful exploration of extrahepatic collaterals during TACE may prevent this complication.

Impact of gastric bypass treatment and hepatic branch of the vagus on hypoglycemic outcome in rats with type 2 diabetes

Objective To observe the effect of Roux-en-Y gastric bypass(RYGB)treatment and hepatic branch of the vagus on hypoglycemic outcome and glucagon-like peptide-1(GLP-1)in rats with type 2 diabetes,and the interaction of between the two.Methods Totally 45 type 2 diabetic rats were divided into four groups:sham operation(S group,n=10),sham operation with hepatic branch of the vagus resected(SV group,n=11),RYGB group(n=12),and RYGB with hepatic branch of the vagus resected(RYGBV group,n=12).The body mass,fasting blood-glucose(FBG),fasting serum insulin(FINS)and concentrations of fasting serum GLP-1 were examined before and after surgery.Effects of RYGB and the hepatic branch of the vagus on GLP-1 levels were analyzed.Results Compared with S group and RYGBV group,RYGB group had significantly decreased body mass(P0.05)and significantly improved levels of serum GLP-1 and insulin(P0.05);FBG level in RYGB group was significantly lower than that in S group(P0.05)and similar to that in RYGBV group.The effect of RYGB on fasting serum GLP-1 was stronger than that of liver branch of the vagus nerve,and there was interaction between the two(P0.05).Conclusion RYGB treatment has satisfactory treatment effect for type 2diabetes,and care should be taken during RYGB surgery to preserve the hepatic branch of the vagus.

Organ-Specific Activation of the Gastric Branch of the Efferent Vagus Nerve by Ghrelin in Urethane-Anesthetized Rats

Ghrelin plays multiple physiological roles such as growth hormone secretion and exerting orexigenic actions; however, its physiological roles in the electrical activity of autonomic nerves remain unclear. Here, we investigated the effects of human ghrelin on several autonomic nerve activities in urethane-anesthetized rats using an electrophysiological method. Intravenous injection of ghrelin at 3 μg/kg significantly and transiently potentiated the efferent activity of the gastric vagus nerve; however, it did not affect the efferent activity of the hepatic vagus nerve. The activated response to ghrelin in the gastric efferent vagus nerve was not affected by the gastric afferent vagotomy, suggesting that this effect was not induced via the gastric afferent vagus nerve. Ghrelin did not affect the efferent activity of the brown adipose tissue, adrenal gland sympathetic nerve, and the renal sympathetic nerve. In addition, rectal temperature and the plasma concentrations of norepinephrine, corticosterone, and renin were also not changed by ghrelin. These findings demonstrate that ghrelin stimulates the gastric efferent vagus nerve in an organ-specific manner without affecting the gastric afferent vagus nerve and that ghrelin does not acutely affect the efferent basal activity of the sympathetic nerve in rats.

A Study of the Brain Mechanisms Related to Recognition of Food Intake and Maintenance of Amino Acid Homeostasis in Rats

It has been revealed that the brain mechanisms related to cognition of and adaptation to L-lysine (Lys) deficiency in rats involve the lateral hypothalamic area (LHA) and related nuclei controlling appetite and food preference, and that intake of particular nutrients shows plasticity in response to Lys in the diet. Similar plastic changes occur in the nucleus solitalis in response to gustatory and visceral information. This plasticity is induced by activin A activity in the brain. In addition, highly plastic changes in the LHA associated with auditory, olfactory and gustatory triggers are also observed. It has been demonstrated quantitatively that rats with Lys deficiency show a tendency to ingest Lys from among a variety of amino acids in solution, and display a preference for monosodium L-glutamate (MSG) solution while reducing their intake of sodium chloride, indicating normalization of protein nutrition status. With regard to other nutritional roles of free L-glutamate, it has been clarified that the vagal afferent fibers in the gastric branch respond specifically to glutamate alone, contributing to cognition of food intake and subsequent control of digestion, absorption and metabolism for efficient nutrient utilization in the body. Furthermore, this glutamate signaling from the stomach to the brain stimulates learning and memory function, as well as diet-induced thermogenesis, preventing the development of obesity.

Unusual presentation and treatment of spontaneous celiac artery dissection

The management options of an isolated celiac artery dissection include medical, open surgical, and endovascular techniques. Which strategy is chosen depends on the severity of the dissection, collateral circulation to the liver, the patient's hemodynamic status, and the surgeon's expertise. We describe an unusual case of celiac artery dissection involving splenic and hepatic arteries complicated by hemorrhage. The patient was successfully treated by coil embolization of the splenic and gastric branches. Hepatic arterial blood flow was preserved with a stent graft extending from the origin of the gastroduodenal artery to the orifice of the celiac artery.

Anatomy of the Anterior Vagus Nerve: An Anatomic Description and its Application in Surgery

Objective: Anatomic study of human corpses in order to obtain specific measurements of the anterior vagus nerve for its application in the surgical field. Methods: After analyzing the literature, dissections were performed on 15 human corpses, provided by the Universidad del Salvador. Descriptions were made of our observations. Results: The most frequently found structure in esophageal hiatus was a plexus. The cardial branch was present in 100% of the dissections. There were a constant number of gastric branches, between five and seven. The hepatic branch originated from the plexus in the majority of the cadavers. The distance between first and last branch points was variable. No relationship between the hepatic branch and left hepatic artery was observed. Conclusions: The structure most commonly found in the esophageal hiatus was the terminal plexus of the anterior vagus nerve. The hepatic branch most frequently originated directly from this plexus, although in a considerable number of cases its origin was found either proximal or distal to this structure. We could not confirm the literature stating the relationship between the hepatic branch and the left hepatic artery through our studies. The number of gastric branches was constant. The distance between the first and last gastric branch was extremely variable, which can be explained by the anthropometric differences between the cadavers. No relationship was found between the number of gastric branches and the length of the main gastric branch.

Collateral projections of the dorsal motor nucleus of the vagus nerve to the stomach and the intestines in the rat

The vagal motor neurons project to the gastrointestinal tract by way of the gastric, celiac and hepatic branches of the vagus trunk. We have examined whether single neurons in the dorsal motor nucleus of the vagus nerve (DMV) have collateral projections to the stomach, the duodenum and the intestines using a double-labeling tracing method. Following application of Fluorogold to the cut end of the accessory celiac branch and injection of cholera toxin subunit b (CTb) into the body of stomach, many Fluorogold- and CTb-labeled neurons were found throughout the DMV. Most CTb-labeled neurons (about 90%) were also labeled with Fluorogold. When Fluorogold was applied to the cut end of the accessory celiac or the gastric branch and CTb was injected into the duodenum, many Fluorogold-labeled neurons and CTb-labeled neurons were found in the DMV. About 20% of CTb-labeled neurons were also labeled with Fluorogold. These results indicate that many neurons in the DMV send collateral projections to both the stomach and the intestines innervated by way of the celiac branch. However, many neurons in the DMV projecting to the duodenum do not project to the stomach or the intestines caudal to the duodenum.

Essential Elements for Glucosensing by Gastric Vagal Afferents: Immunocytochemistry and Electrophysiology Studies in the Rat

Glucosensing nodose ganglia neurons mediate the effects of hyperglycemia on gastrointestinal motility. We hypothesized that the glucose-sensing mechanisms in the nodose ganglia are similar to those of hypothalamic glucose excited neurons, which sense glucose through glycolysis. Glucose metabolism leads to ATP-sensitive potassium channel (K(ATP)) channel closure and membrane depolarization. We identified glucosensing elements in the form of glucose transporters (GLUTs), glucokinase (GK), and K(ATP) channels in rat nodose ganglia and evaluated their physiological significance. In vitro stomach-vagus nerve preparations demonstrated the gastric vagal afferent response to elevated glucose. Western blots and RT-PCR revealed the presence of GLUT1, GLUT3, GLUT4, GK, and Kir6.2 in nodose ganglia neurons and gastric branches of the vagus nerve. Immunocytochemistry confirmed the expression of GLUT3, GK, and Kir6.2 in nodose ganglia neurons (46.3 ± 3%). Patch-clamp studies detected glucose excitation in 30% (25 of 83) of gastric-projecting nodose ganglia neurons, which was abolished by GLUT3 or GK short hairpin RNA transfections. Silencing GLUT1 or GLUT4 in nodose ganglia neurons did not prevent the excitatory response to glucose. Elevated glucose elicited a response from 43% of in vitro nerve preparations. A dose-dependent response was observed, reaching maximum at a glucose level of 250 mg/dl. The gastric vagal afferent responses to glucose were inhibited by diazoxide, a K(ATP) channel opener. In conclusion, a subset of neurons in the nodose ganglia and gastric vagal afferents are glucoresponsive. Glucosensing requires a GLUT, GK, and K(ATP) channels. These elements are transported axonally to the gastric vagal afferents, which can be activated by elevated glucose through modulation of K(ATP) channels.

Tu1451 Retrograde Axonal Transport of Fluorogold Was Reduced in Gastric Ascending, but Not Descending, Enteric Neurons in Type 2 Diabetic Kkay as Compared to Control Kk Mice

Retrograde axonal transport was impaired in the gastric branch of the vagus nerve in animals with type 1 diabetes mellitus (DM). These studies evaluated active, retrograde axonal transport of the neural tracer fluorogold (FG) in gastric enteric neurons in KKAy mice 4 weeks prior to and at the onset of type 2 DM, and after 8, 16, and 24 weeks of uncontrolled DM. We hypothesized that the number of FG-labeled enteric neurons would progressively decrease with increasing durations of uncontrolled DM as compared to control KK mice. Under anesthesia, FG was injected into the ventral fundus or antrum. After 5-6 days, the stomach was removed and the numbers of FG-labeled enteric neurons with cell bodies in 2.8 mm2 of fundus, 1.7 mm2 of corpus, and 1.7 mm2 of antrum were counted. The total number of FG-labeled neurons in ascending pathways (cell bodies in corpus or antrum with nerve terminals in fundus), descending pathways (cell bodies in the fundus or corpus with nerve terminals in antrum), the local fundic pathway (cell body and nerve terminals in fundus), and the local antral pathway (cell body and nerve terminals in antrum) were compared in control and diabetic mice of different ages by 2-way ANOVA. Only main effects were significant; no interactions were significant. Data are mean±SEM with n representing the number of mice. In the ascending pathway, fewer FG-labeled neurons were observed in diabetic as compared to control mice [F(1,116)=10.668; control (n=68), 179±11; diabetic (n= 58), 145±11*; *p<0.05]. In contrast, similar numbers of FG-labeled neurons were observed in descending pathways [F(1,124)=0.489; p=0.486], local fundic pathways [F(1,53)=2.464; p=0.122], and local antral pathways [F(1,57)=0.728; p=0.397] of control and diabetic mice. Overall, the number of FG-labeled neurons decreased significantly with age in all pathways [ascending: F(4,116)=42.862; descending: F(4,124)=2.456; local fundic: F(4,53)=5.195; local antral: F(4,57)=8.920]. In the ascending pathway, the number of FG-labeled neurons was significantly less at 16 weeks of age [n=28, 146±12] as compared to 4 weeks [n=24, 246±8] or 8 weeks [n=28, 229±12] of age, reaching its lowest value at 24 weeks of age [n= 24, 80±10]. In conclusion, DM did not uniformly impair active tracer transport in all gastric enteric neurons suggesting specific axonal targets in ascending enteric neurons rendering them more susceptible to hyperglycemia and low effective insulin. Supported by ORSP at MWU.

Tu1452 Enteroglial-Derived S100B Protein Modulates Differentiation and Proliferation of Human Intestinal Epithelial Cells in a RAGE-Dependent Manner

Retrograde axonal transport was impaired in the gastric branch of the vagus nerve in animals with type 1 diabetes mellitus (DM). These studies evaluated active, retrograde axonal transport of the neural tracer fluorogold (FG) in gastric enteric neurons in KKAy mice 4 weeks prior to and at the onset of type 2 DM, and after 8, 16, and 24 weeks of uncontrolled DM. We hypothesized that the number of FG-labeled enteric neurons would progressively decrease with increasing durations of uncontrolled DM as compared to control KK mice. Under anesthesia, FG was injected into the ventral fundus or antrum. After 5-6 days, the stomach was removed and the numbers of FG-labeled enteric neurons with cell bodies in 2.8 mm2 of fundus, 1.7 mm2 of corpus, and 1.7 mm2 of antrum were counted. The total number of FG-labeled neurons in ascending pathways (cell bodies in corpus or antrum with nerve terminals in fundus), descending pathways (cell bodies in the fundus or corpus with nerve terminals in antrum), the local fundic pathway (cell body and nerve terminals in fundus), and the local antral pathway (cell body and nerve terminals in antrum) were compared in control and diabetic mice of different ages by 2-way ANOVA. Only main effects were significant; no interactions were significant. Data are mean±SEM with n representing the number of mice. In the ascending pathway, fewer FG-labeled neurons were observed in diabetic as compared to control mice [F(1,116)=10.668; control (n=68), 179±11; diabetic (n= 58), 145±11*; *p<0.05]. In contrast, similar numbers of FG-labeled neurons were observed in descending pathways [F(1,124)=0.489; p=0.486], local fundic pathways [F(1,53)=2.464; p=0.122], and local antral pathways [F(1,57)=0.728; p=0.397] of control and diabetic mice. Overall, the number of FG-labeled neurons decreased significantly with age in all pathways [ascending: F(4,116)=42.862; descending: F(4,124)=2.456; local fundic: F(4,53)=5.195; local antral: F(4,57)=8.920]. In the ascending pathway, the number of FG-labeled neurons was significantly less at 16 weeks of age [n=28, 146±12] as compared to 4 weeks [n=24, 246±8] or 8 weeks [n=28, 229±12] of age, reaching its lowest value at 24 weeks of age [n= 24, 80±10]. In conclusion, DM did not uniformly impair active tracer transport in all gastric enteric neurons suggesting specific axonal targets in ascending enteric neurons rendering them more susceptible to hyperglycemia and low effective insulin. Supported by ORSP at MWU.

Abdominal vagal afferent pathways and their distributions of intraganglionic laminar endings in the rat duodenum

We examined abdominal vagal afferents (n = 33) and the distributions of their intraganglionic laminar endings (IGLEs) in the duodenum. Rats (male, Sprague-Dawley) received a partial subdiaphragmatic vagotomy that spared a single branch. Wheat germ agglutinin-horseradish peroxidase (0.5-1.0 μl) was injected into the nodose ganglion ipsilateral to the vagotomized side. We observed that the hepatic branch does not project to the stomach, that the accessory celiac and celiac branches course along the celiac artery and innervate the intestines, and that the left nodose afferents innervate predominantly the duodenum. The hepatic branch innervates the duodenum via the "hepatoduodenal" subbranch and has the densest IGLE distribution in both the dorsoventral and the rostrocaudal extensions of the first 4-cm segment. Both gastric branches have two subbranches that innervate the duodenum; the "lesser curvature" subbranches follow the lesser curvature artery and may join the "hepatoduodenal" subbranch, whereas the "pyloric" subbranches run through the antrum and pylorus to reach the proximal duodenum. Moreover, the subbranches of ventral and dorsal gastric branches innervate more in the ventral and dorsal parts of the duodenum, respectively, and have more IGLEs in the rostral region than in the caudal. A posteriori comparisons indicate that, in the first-centimeter segment, the ventral gastric branch has significantly more IGLEs, whereas, in the third- and fourth-centimeter segments, the hepatic branch has more IGLEs. The finding that three different vagal branches innervate the duodenum with different densities of afferent endings might indicate a viscerotopic receptive field that coordinates digestive functions in feeding.

New Therapeutic Strategy for Amino Acid Medicine: Effects of Dietary Glutamate on Gut and Brain Function

The gustatory and visceral stimulation from food regulates digestion and nutrient utilization, and free glutamate (Glu) release from food is responsible for the umami taste perception that increases food palatability. The results of recent studies reveal a variety of physiological roles for Glu. For example, luminal applications of Glu into the mouth, stomach, and intestine increase the afferent nerve activities of the glossopharyngeal nerve, the gastric branch of the vagus nerve, and the celiac branch of the vagus nerve, respectively. Additionally, luminal Glu evokes efferent nerve activation of each branch of the abdominal vagus nerve. The intragastric administration of Glu activates several brain areas (e.g., insular cortex, limbic system, and hypothalamus) and has been shown to induce flavor-preference learning in rats. Functional magnetic resonance imaging of rats has shown that the intragastric administration of Glu activates the nucleus tractus solitarius, amygdala, and lateral hypothalamus. In addition, Glu may increase flavor preference as a result of its postingestive effect. Considering these results, we propose that dietary Glu functions as a signal for the regulation of the gastrointestinal tract via the gut–brain axis and contributes to the maintenance of a healthy life.

Potential underlying mechanisms for greater weight gain in massaged preterm infants

In this paper, potential underlying mechanisms for massage therapy effects on preterm infant weight gain are reviewed. Path analyses are presented suggesting that: (1) increased vagal activity was associated with (2) increased gastric motility, which, in turn, was related to (3) greater weight gain; and (4) increased IGF-1 was related to greater weight gain. The change in vagal activity during the massage explained 49% of the variance in the change in gastric activity. And, the change in vagal activity during the massage explained 62% of the variance in the change in insulin. That the change in gastric activity was not related to the change in insulin suggests two parallel pathways via which massage therapy leads to increased weight gain: (1) insulin release via the celiac branch of the vagus; and (2) increased gastric activity via the gastric branch of the vagus.

P-90: Selective vagotomy during laparoscopic roux-en- Y gastric bypass does not lead to additional morbidity

Gastric pouch creation during laparoscopic Roux-en-Y Gastric Bypass (LRYGB) requires access to the lesser sac. This is usually achieved by developing a perigastric plane between the lesser curve of the stomach and its mesentery. Frequently, this is tedious and leads to complications such as gastric wall injury and bleeding. Approaching the lesser sac through the transparent portion of the gastrohepatic ligament (pars flaccida) allows for an easier and safer approach. This technique, however, results in transection of one of the gastric branches of the anterior nerve of Laterjet.

Existence of NO-triggered vagal afferent activation in the rat gastric mucosa

We previously reported the possible involvement of mucosal nitric oxide (NO)-triggered 5-HT release in luminal glutamate sensing by the gastric vagus nerve, and we proposed that the stomach, like the duodenum, could "taste" luminal nutrients. Nitric oxide synthase (NOS) is widely distributed in the gastric mucosa, but the physiological role of mucosal NO is not well understood. In this study, we investigated the functional coupling of NO and vagal nerve endings in the gastric mucosa. For electrophysiological recordings, male Sprague-Dawley rats were anesthetized with urethane, and afferent nerve responses of rat vagal gastric branches to a NO donor were monitored. Intravenous application of 100microg/kg sodium nitroprusside (SNP) transiently increased afferent nerve discharges of the rat ventral gastric vagus, which was followed by rapid changes in blood pressure. High doses of SNP (>300microg/kg, i.v.) showed a biphasic increase in afferent discharges. Secondary activation of the vagal afferent continued even after blood pressure returned to basal levels. SNP-evoked afferent responses were abolished by mucosal 5-HT depletion using p-cholorophenylalanine and were inhibited by pre- and post-treatment with the 5-HT(3) antagonist granisetron. These pharmacological results strongly indicate that NO-triggered 5-HT release is coupled to vagal afferent activation in the rat gastric mucosa.

First experience of hepatic radioembolization using microspheres labelled with yttrium-90 (TheraSphere): practical aspects concerning its implementation

We report a first experience involving the use of (90)Y radiolabelled microspheres (TheraSphere) for the treatment of mainly primary hepatic tumours. Treatment using TheraSphere microspheres was planned in 15 patients (13 with hepatocellular carcinoma, 2 with neuroendocrine tumour metastases). The treatment was preceded by a first angiography aimed at embolizing the vascularizing arterial branches of other structures outside the liver and evaluating the percentage of pulmonary shunt by scintiscanning after perfusion with (99m)Tc-MAA. The objective of the treatment carried out during a second angiography was to deliver a dose of 120+/-20 Gy (mean+/-SD) to the target hepatic volume. Technical difficulties were encountered in embolizing gastroduodenal or gastric branches in two patients and in one patient these led to cancellation of the treatment. A total of 14 patients were treated with an average activity of 3.18 GBq. In one patient, the injection was defective (stagnation of microspheres at the outlet of the catheter). SPECT/CT acquisitions provided important information in four patients (visualization of the gallbladder in three; visualization of the stomach in one, leading to a new coiling). The average exposure of the nuclear medicine physician carrying out the injections was 64+/-80 microSv at the fingers. A partial response was seen in six patients, stabilization in five and progression in three. One patient presented with a gastric ulcer and two showed an increase in their hepatocellular insufficiency. Although sometimes technically difficult, the use of TheraSphere microspheres is a worthwhile therapeutic approach because of the low level exposure of operators and the encouraging rate of response or stabilization. The use of SPECT/CT contributes greatly to helping therapeutic planning, especially in the learning curve or when the angiographic procedure is difficult.

Receptor‐mediated activation of gastric vagal afferents by glucagon‐like peptide‐1 in the rat

The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague-Dawley rats. Intravenous administration of GLP-1 (30-1000 pmol kg(-1)), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13-52% above basal level, P < 0.05) 3-5 min after injection. Repeated administration of GLP-1 (1000 pmol kg(-1); five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg(-1)) abolished the GLP-1 response to doses 30-300 pmol kg(-1) but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg(-1)) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents.