Combined Vagotomy Research Articles

A dual mechanism fully blocks ethanol relapse: Role of vagal innervation.

Previous studies showed that vagotomy markedly inhibits alcohol self-administration. Present studies hypothesised that vagotomy significantly adds to the inhibition of alcohol relapse induced by drugs that reduce the alcohol-induced hyperglutamatergic state (e.g., N-acetylcysteine + acetylsalicylic acid). The alcohol relapse paradigm tested gauges the elevated alcohol intake observed in animals that had consumed ethanol chronically, were subjected to a prolonged alcohol deprivation and are subsequently allowed ethanol re-access. Ethanol-drinker rats (UChB) were exposed to 10% and 20% ethanol and water concurrently for 4months, were alcohol deprived for 14 days and were thereafter allowed re-access to the ethanol solutions. An initial binge-like drinking episode is observed upon ethanol re-access, followed by a protracted elevated ethanol intake that exceeds the predeprivation intake baseline. Prior to ethanol re-access, animals were (i) administered N-acetylcysteine (40 mg/kg/day) + acetylsalicylic acid (15 mg/kg/day), (ii) were bilaterally vagotomised, (iii) were exposed to both treatments or (iv) received no treatments. The initial binge-like relapse intake and a protracted elevated ethanol intake observed after repeated ethanol deprivations/re-access cycles were inhibited by 50%-70% by the administration of N-acetylcysteine + acetylsalicylic acid and by 40%-70% by vagotomy, while the combined vagotomy plus N-acetylcysteine + acetylsalicylic acid treatment inhibited both the initial binge-like intake and the protracted ethanol intake by >95% (p < 0.001), disclosing a dual mechanism of ethanol relapse and subsequent inhibition beyond that induced by either treatment alone. Future exploration into the mechanism by which vagal activity contributes to ethanol relapse may have translational promise.

Regression of intestinal metaplasia to cardiac or fundic mucosa in patients with Barrett's esophagus submitted to vagotomy, partial gastrectomy and duodenal diversion. A prospective study of 78 patients with more than 5 years of follow up

Regression of intestinal metaplasia to cardiac mucosa in patients with Barrett's (BE) esophagus could alter the natural history of BE. To determine the regression of intestinal metaplasia to cardiac mucosa in patients followed more than 5 years after operation, by repeated endoscopy with biopsy. This prospective study included 78 patients with BE submitted to combined vagotomy, antrectomy (an antireflux procedure), and Roux-en-Y gastrointestinal reconstruction with more than 60 months follow up. Patients were divided in 3 groups: (1) 31 with short-segment BE (< or =30 mm length); (2) 42 with long-segment BE (31 to 99 mm length); and (3) 5 with extra-long-segment BE (> or =100 mm). Each patient had at least three endoscopic procedures with multiple biopsies during a mean follow up of 95 months (range, 60-220 months). Acid and duodenal reflux were also evaluated. Sixty-four percent of patients with short segment BE had regression to cardiac mucosa at a mean of 40 months after operation. Sixty-two percent of patients with long segment BE had regression to cardiac mucosa at a mean of 47 months postoperatively. No regression occurred in the 5 patients with extra-long segment BE. In 20% of patients, regression to fundic mucosa occurred between 78 to 94 months after surgery. One patient progressed to low grade dysplasia, but no patient progressed to high-grade dysplasia or adenocarcinoma. Acid and duodenal reflux studies demonstrated that in asymptomatic patients, reflux was abolished; 90% of the patients had a Visick grade of 1 or 2. Vagotomy and antrectomy combined with duodenal bile diversion abolish acid and duodenal reflux into the distal esophagus in patients with BE, which is accompanied by a regression of BE from intestinal to cardiac or fundic mucosa in about 60% of patients. This regression is time dependent and varies directly with the length of BE. The potential for an antineoplastic effect, especially in young patients with long segment BE, suggests that this operation may become an attractive option as a definitive surgical treatment. Patients with short segment BE submitted to this procedure behave similar to patients submitted to Nissen fundoplication, and therefore in these patients, we do not advocate this complex operation.

Preference for proximal gastric vagotomy combined with cholecystectomy.

The incidence and severity of postvagotomy diarrhoea has been studied in 32 patients who had undergone both vagotomy and cholecystectomy. Sixteen of these patients had had a proximal gastric vagotomy and 16 a truncal vagotomy and pyloroplasty. Diarrhoea was present in 68 per cent of patients in whom the vagotomy was truncal and in 31 per cent of those in whom it was proximal gastric. Matched groups of patients with truncal vagotomy with pyloroplasty and proximal gastric vagotomy without cholecystectomy were also compared. The possible mechanisms of this diarrhoea following combined vagotomy and cholecystectomy have been discussed.

Vagal and splanchnic afferent nerves are not essential for anorexia associated with abomasal parasitism in sheep

Heavy burdens of the abomasal nematode, Ostertagia ( Telodorsagia) circumcincta, in growing lambs result in a reduction in liveweight gain due largely to a drop in voluntary feed intake. The present study investigated: (1) the role of subdiaphragmatic vagal and non-vagal visceral afferent nerves in mediating a reduction in voluntary feed intake, using subdiaphragmatic vagal deafferentation (vagotomy) either alone or in combination with coeliac-superior mesenteric ganglionectomy (vagotomy and sympathectomy); and (2) the association between appetite, abomasal pH, selected blood values (amidated gastrin (G-17-amide), glycine-extended gastrin (G-17-Gly), pepsinogen and leptin) and worm burden, in sheep experimentally infected with 100 000 O. circumcincta infective larvae per os. Neither vagotomy alone nor vagotomy and sympathectomy in combination adversely affected the establishment or course of development of the parasite burden, when compared with a control group subject to sham surgery. Furthermore, neither surgical procedure prevented the drop in appetite seen 5–10 days post-infection, although combined vagotomy and sympathectomy did reduce voluntary feed intake prior to the start of the study. Ostertagia infection resulted in a significant increase in abomasal pH in all three groups, which was accompanied by an increase in blood G-17-amide and in G-17-Gly, the latter reported for the first time in parasitized ruminants. There were no significant differences in blood leptin, also reported for the first time in parasitized sheep, either between groups or in comparison with pre-infection levels, though weak negative correlations were established between blood leptin and appetite from day 5 to the end of the study in all three groups and a positive correlation with blood G-17-amide in the control group over the same period. These data suggest that neither intact subdiaphragmatic vagal afferent nerves or coeliac-superior mesenteric ganglion fibres, nor changes in circulating gastrin and leptin concentrations play a major role in mediating the hypophagic effects of O. circumcincta in parasitized sheep.

Gonadal hormones do not account for sexual dimorphism in vagal modulation of nociception in the rat

Subdiaphragmatic vagotomy produces a decrease in mechanical nociceptive threshold that is greater in male rats and an enhancement of bradykinin hyperalgesia that is greater in female rats. To examine the role of gonadal hormones in these sex differences, we evaluated the effect of gonadectomy, with or without gonadal hormone replacement, on vagal modulation of nociceptive threshold and bradykinin hyperalgesia by using the Randall-Selitto paw withdrawal test. Gonadectomy (before sexual maturation) plus vagotomy decreased nociceptive threshold in male rats more than either lesion alone, whereas neither lesion nor in combination had an effect on nociceptive threshold in female rats. Testosterone or dihydrotestosterone replacement in gonadectomized plus vagotomized males and 17β-estradiol in females did not significantly alter nociceptive threshold compared to vagotomy plus gonadectomy, respectively. Combined vagotomy and gonadectomy unexpectedly almost completely abolished bradykinin hyperalgesia, whereas gonadectomy alone had no effect on bradykinin hyperalgesia in both sexes. Testosterone replacement in vagotomized males and 17β-estradiol in vagotomized females reversed the effect of gonadectomy. Dihydrotestosterone replacement in vagotomized males also reversed the effect of gonadectomy on bradykinin hyperalgesia, although to a lesser degree than testosterone. We conclude that although gonadal hormones and other gonadal-dependent mechanisms influence nociception, they do not account for sexual dimorphism in vagal modulation of mechanical nociceptive threshold or bradykinin hyperalgesia.

Effects of vagal and splanchnic section on food intake, weight, serum leptin and hypothalamic neuropeptide Y in rat

Truncal vagotomy can cause reduced food intake and weight loss in humans and laboratory animals. In order to investigate some of the factors that might contribute to this effect, we studied changes in ingestive behaviour, whole body and organ weights, serum leptin and hypothalamic neuropeptide Y in rats with bilateral vagal section, bilateral splanchnic nerve section and combined vagotomy plus splanchnectomy. Pyloromyotomy was combined with vagotomy to lessen effects of vagotomy on gastric emptying. Animals with vagotomy or vagotomy plus splanchnectomy lost weight and decreased their daily food intake relative to animals with splanchnectomy alone, rats with bilateral sham exposure of one or both nerve, or rats with pyloromyotomy alone. Serum leptin and white fat mass, 4 weeks after vagotomy, were about 20% of the values in the sham-operated animals at this time. No effect for splanchnic nerve section alone was observed. Pyloromyotomy caused no reduction in weight or fat mass, but reduced serum leptin. Following vagotomy with or without splanchnic nerve section, neuropeptide Y was elevated in the arcuate nucleus relative to values for the other four groups. Changes in neuropeptide Y were inversely correlated with levels of serum leptin. It is concluded that the effect of vagotomy could be due to the loss of a feeding signal carried by vagal afferent neurons, or to changed humoral signals, for example, increased production of a satiety hormone. However, it cannot be attributed to signals that reduce feeding (for example, gastric distension) reaching the central nervous system via the splanchnic nerves. The changes were sufficient to cause weight loss even though serum leptin was decreased, a change that would be expected to increase food intake.

Vagal and splanchnic afferents are not necessary for the anorexia produced by peripheral IL-1beta, LPS, and MDP.

We investigated the extrinsic gut neural mediation of the suppression of food intake in male Sprague-Dawley rats induced by peripheral intraperitoneal administration of 2 microg/kg interleukin-1beta (IL-1beta), 100 microg/kg bacterial lipopolysaccharide (LPS), and 2 mg/kg muramyl dipeptide (MDP). Food intake during the first 3 and 6 h of the dark cycle was measured in rats with subdiaphragmatic vagal deafferentation (n = 9), celiac superior mesenteric ganglionectomy (n = 9), combined vagotomy and ganglionectomy (n = 9), and sham deafferentation (n = 9). IL-1beta, LPS, and MDP suppressed food intake at 3 and 6 h in all surgical groups. The results demonstrate that neither vagal nor nonvagal afferent nerves from the upper gut are necessary for the feeding-suppressive effects of intraperitoneal IL-1beta, LPS, or MDP in the rat and suggest that peripheral administration of immunomodulators produces anorexia via a humoral pathway.

Evidence that myenteric neurons of the gastric corpus project to both the mucosa and the external muscle: myectomy operations on the canine stomach

The distribution of nerve cell bodies and fibres in the canine stomach was investigated using antibodies to the general neuronal marker, neuron-specific enolase. Prominent ganglia containing many reactive nerve cells were found in the myenteric plexus of the gastric corpus and antrum. Nerve cells were absent from the submucosa of the corpus and were extremely rare in the antrum. Removal of areas of longitudinal muscle and myenteric plexus from the corpus (myectomy), with 7 days allowed for axon degeneration, resulted in the loss of fibres reactive for galanin, gastrin-releasing peptide, substance P and vasoactive intestinal peptide from both the circular muscle and mucosa in the area covered by the lesion. Combined vagotomy and sympathetic denervation did not significantly affect these fibres, but did cause fibres reactive for calcitonin gene-related peptide to degenerate. It is concluded that the myenteric plexus of the gastric corpus, like the myenteric plexus of the small intestine and colon, is the source of nerve fibres innervating the circular muscle, but, in contrast to other regions of the gastrointestinal tract, myenteric ganglia, not submucous ganglia, are the major, or sole, source of the intrinsic innervation of the mucosa.

Vagal cardiopulmonary baroreflex activation during phenylephrine infusion.

Phenylephrine infusion (PE) has been used to raise arterial pressure (BP) in order to investigate reflex responses mediated by sinoaortic baroreflexes (SAB). Increases in cardiac filling pressures have been reported during PE. Our experiments determined whether PE selectively activates SAB without activation of vagal cardiopulmonary baroreflexes (CPR). We measured changes in mean BP, mean pulmonary arterial pressure (PAP), and renal sympathetic nerve activity (RSNA) during PE in alpha-chloralose-anesthetized dogs before and after sinoaortic denervation (SAD; n = 10), selective vagotomy (n = 9), or SAD and vagotomy (n = 4). PE elevated both BP and PAP in all dogs studied. In dogs with SAB and CPR intact, RSNA was reflexively inhibited (% change RSNA: -76.3 +/- 4.7). In SAD dogs, inhibition of RSNA was significantly attenuated but not abolished (% change RSNA: -27.5 +/- 11.8). This inhibition after SAD correlated closely with increases in PAP. Small BP changes (10 mmHg) were associated with insignificant changes in PAP and RSNA. Volume expansion after SAD produced changes in PAP and RSNA similar to those produced by PE. After selective vagotomy, the sensitivity (% change RSNA/mmHg change BP) of the reflex elicited by PE was significantly decreased (-2.7 +/- 0.03 pre vs. -1.8 +/- 0.12 post; P = 0.01). PE failed to change RSNA after combined SAD and vagotomy. We conclude that vagal CPR contribute to reflex inhibition of RSNA during PE except when elevations of BP are small.

Glycine microinjected in the rat dorsal vagal nucleus increases arterial pressure.

Microinjections (25 nl) of glycine into the dorsal motor nucleus of the vagus in 21 rats elicited dose-dependent increases of arterial pressure and heart rate that were not seen with injections adjacent to the dorsal motor nucleus of the vagus. The responses to glycine were neurally mediated and could be blocked either by local pretreatment with strychnine or by combined vagotomy and ganglionic blockade. The data suggest that glycine receptors on, or in the region of, neurons of the dorsal motor nucleus of the vagus may have a role in the regulation of arterial pressure and heart rate.

Effect of vagotomy and thoracic sympathectomy on responses of the monkey to water immersion.

Cardiopulmonary stretch receptors have been implicated as part of a reflex mechanism linking changes in blood volume to changes in renal excretion. Experiments were performed to determine whether total denervation of these receptors by combined cervical vagotomy and thoracic sympathectomy affects the renal responses of the monkey to head-out water immersion, a maneuver that translocates blood to the thorax and elicits an increase in renal salt and water excretion. Macaca fascicularis monkeys first underwent chronic bilateral thoracic sympathectomy or sham denervation performed in two stages a week apart. One to two weeks later, they were anesthetized with pentobarbital sodium, and the sympathectomized animals underwent bilateral cervical vagotomy. Control renal function did not differ between the two groups. Immersion of 90-min duration increased central venous and mean arterial pressures by similar amounts in both groups, but heart rate increased only in the sham-denervated animals. Denervation did not affect the magnitudes or delay the times of onset of the increases in urine flow, absolute and fractional sodium excretion, and osmolar and free water clearances occurring with immersion. These results demonstrate that in the anesthetized monkey cardiopulmonary receptors are not necessary for eliciting the renal responses to immersion.

Cardiorespiratory responses to chemical activation of right ventricular receptors.

Previous reports have shown that activation of left ventricular receptors with sympathetic afferents elicits increases in respiratory output and arterial pressure. The purpose of the present study was to determine whether similar responses are produced by chemical activation of epicardial receptors in the right ventricle. Receptors were stimulated by applying either capsaicin (10 micrograms) or bradykinin (500 ng) to the epicardial surface of the right ventricle in anesthetized cats. Application of either chemical evoked an increase in respiratory output (phrenic nerve activity), a decrease in heart rate, and a nonsignificant increase in arterial pressure in intact cats. However, capsaicin and bradykinin produced significant increases in arterial pressure, heart rate, and respiratory output after bilateral cervical vagotomy. In contrast, a fall in both heart rate and arterial pressure with only small increases in respiratory output were evoked after bilateral removal of the stellate ganglia in cats with intact vagi. Only small responses to the chemical stimulation of right ventricular receptors persisted after combined vagotomy and stellate ganglionectomy. These findings suggest that 1) activation of epicardial receptors with sympathetic afferents originating in the right ventricle causes an increase in cardiorespiratory function, and 2) activation of right ventricular receptors with vagal afferents produces decreases in heart rate and arterial pressure.

Vagotomy inhibits the effect of neurotensin on gastrointestinal transit in the rat.

Neurotensin has previously been shown to delay gastric emptying, gastrointestinal transit and ileo-caecal emptying in the rat. To investigate the vagal influence on these effects of neurotensin, separate groups of rats were operated with combined vagotomy and pyloroplasty or with pyloroplasty alone and compared to a group of normal rats. All animals were supplied with a permanent gastrointestinal catheter and a venous catheter. After operation the rats were allowed to recover for 7 days, and were fasted for 24 h prior to the experiments. A radioactive marker of 1.0-0.5 ml Na2(51)CrO4 in isotonic polyethylene glycol 400 was instilled intraluminally in the stomach, proximal or distal the small intestine. Saline (control animals) or neurotensin (test animals) was given i.v. in each group studied. The animals were killed at 15, 30, 60, and 120 min after administration of the marker. The distribution of the marker in the gastrointestinal tract was registered with a scintillation detector and quantitative analysis of the amount of radioactivity retained in separate gastrointestinal segments was carried out. Gastric emptying was delayed by combined vagotomy and pyloroplasty (P less than 0.01) compared to pyloroplasty alone and normals. Neurotensin at doses of 6 (P less than 0.05) and 12 (P less than 0.01) pmol kg-1 min-1 retarded gastric emptying dose-dependently in normals and rats with pyloroplasty alone, but did not further slow the gastric emptying in rats with vagotomy and pyloroplasty. However, at a dose of 24 pmol kg-1 min-1 neurotensin delayed gastric emptying (P less than 0.01) compared to controls. Gastrointestinal transit was slowed down by neurotensin at a dose of 6 pmol kg-1 min-1 in normals (P less than 0.01) and rats with pyloroplasty alone (P less than 0.05). In rats with vagotomy and pyloroplasty, neurotensin at doses of 6 and 12 pmol kg-1 min-1 had no effect on gastrointestinal transit.(ABSTRACT TRUNCATED AT 250 WORDS)

Capsaicin and regulation of respiration: interaction with central substance P mechanisms.

The neuropharmacological effects of capsaicin (CAPS) (8-methyl-N-vanillyl-6-nonenamide) have been closely linked to the peptide neurotransmitter substance P (SP). In order to elucidate SP mechanisms in peripheral and central control of breathing we have studied the respiratory effects of CAPS and SP administration to neonatal and adult rats using a whole body plethysmographic method. CAPS (3 and 30 micrograms) induced an immediate apnea after intravenous injection. This effect could be reduced by vagotomy but not further changed by combined vagotomy and glossopharyngectomy. The apnoic periods were followed by periods of tachypnea. Intracerebroventricular (i.c.v.) administration of CAPS resulted in an increased tidal volume (VT) and a decreased respiratory frequency (f), i.e. a respiratory response similar to that seen after i.c.v. SP. No apnoic episodes were seen after i.c.v. injection. The respiratory pattern after acute i.c.v. CAPS administration was not significantly changed by neonatal CAPS pretreatment. However, while saline pretreated control animals responded to an i.c.v. injection of SP with an increase in VT and inspiratory drive (VT/TI), animals pretreated with CAPS responded with a shortening of inspiratory and expiratory time in combination with an increase in VT. Similar changes have been observed in vagotomized animals after SP administration. It is concluded that CAPS elicits apnea via mechanisms located outside the CNS, which cannot be fully deafferented by combined vagotomy and glossopharyngectomy. Furthermore, CAPS i.c.v. induces a stimulation of respiration by a central mechanism of action, possibly due to a release of SP. Neonatal pretreatment with CAPS modifies the respiratory response to i.c.v. SP. This effect might be due to an impairment in tonical afferent SP mechanisms to the central respiratory regulating system and possibly also to an impairment of central SP mechanisms involved in respiration.

Effects of Upper Abdominal Sympathectomy on Gastric Acid, Serum Gastrin, and Catecholamines in the Rat Gut

Selective upper abdominal sympathectomy increased basal acid output in rats but was without effect on stimulated acid output, serum gastrin concentration, and gastric mucosal histidine decarboxylase activity. The sympathectomy was verified by fluorescence histochemistry and determination of tissue catecholamines. A drastic reduction in tissue noradrenaline, adrenaline, and dopamine levels occurred after sympathectomy, and fluorescence microscopy showed a complete loss of adrenergic nerve fibers. Vagotomy reduced catecholamine levels in the stomach wall by 50% but did not affect the catecholamine content in the pancreas and small bowel. Surprisingly, combined vagotomy and upper abdominal sympathectomy resulted in lower catecholamine levels than sympathectomy alone in extragastric but not in gastric tissues.

Effects of dopamine, isoproterenol, and lobeline on cranial and phrenic motoneurons.

Recent studies have suggested that the upper airway muscles receive a substantial portion of their excitatory input from the peripheral chemoreceptors. We examined the responses of the phrenic, hypoglossal, and recurrent laryngeal nerves to agents that are known to modify carotid body activity. Dopamine, an inhibitor, and isoproterenol and lobeline, two stimulators of carotid body activity, were administered into the lingual arteries of 14 anesthetized, paralyzed cats artificially ventilated with 100% O2. Dopamine decreased the activity of all three nerves (P less than 0.001) but inhibited the hypoglossal nerve more than the phrenic and recurrent laryngeal nerves (P less than 0.001). Isoproterenol and lobeline increased the activity of all three nerves (P less than 0.001) but stimulated the hypoglossal nerve more than the phrenic and recurrent laryngeal nerves (P less than 0.001). These relatively greater effects of all three agents on the hypoglossal nerve compared with the phrenic and the recurrent laryngeal nerves persisted under both hypoxic and hypercapnic conditions. After midcervical vagotomy, the responses of the hypoglossal to all three drugs remained larger than those of the phrenic nerve. After combined vagotomy and carotid sinus nerve section, the stimulatory effects of lobeline and the inhibitory effects of dopamine were no longer apparent. We conclude that it is possible to preferentially alter respiratory-related activity of the hypoglossal nerve compared with that of the phrenic nerve using agents that modify peripheral chemoreceptor activity.

Gastric mycosis following gastric resection and vagotomy.

In a prospective five-year follow-up study of 289 consecutive patients subjected to antrectomy and gastroduodenostomy with or without vagotomy, 130 patients underwent gastroscopy. Gastric mycosis was present almost exclusively in patients subjected to combined antrectomy and vagotomy (36%). Gastric acidity seemed to be of only minor or no importance in the development of the mycosis. The residual volume in the gastric remnant was significantly higher in patients with gastric mycosis. The impaired emptying of the gastric remnant is most likely a vagotomy effect and may be the main reason for the development of gastric mycosis. A simple but effective method was developed to evacuate gastric yeast cell aggregates. Gastric mycosis seems to give rise to only slight symptoms, mainly nausea and foul-smelling belching, whereas the reflux of duodenal contents that often occurred in combination with gastric mycosis was more likely to cause gastritis and substantial discomfort.

Cerebrovascular response to hypoxia in baroreceptor- and chemoreceptor-denervated dogs.

Cerebral hemodynamic responses to arterial hypoxemia were studied in anesthetized paralyzed dogs that were or that had undergone carotid baroreceptor denervation, carotid chemoreceptor denervation, vagotomy, or both vagotomy and carotid sinus nerve section. Arterial O2 content was lowered from control (19.0 vol%) to 9.6 vol% by either decreasing arterial O2 tension [hypoxic hypoxemia (HH)] or increasing carboxyhemoglobin saturation[carbon-monoxide hypoxemia (COH)] at normal O2 tension. In intact animals (composite control values from all groups) HH and COH resulted in similar increases in cerebral blood flow (to 205 and 197% of control, respectively). Cerebral vascular resistance decreased more with COH than with HH (to 42 vs. 60% of control). The response from carotid baroreceptor-denervated animals and from vagotomized animals did not differ from that of the intact animals. After carotid chemoreceptor denervation and combined carotid sinus nerve section and vagotomy, both HH and COH increased cerebral blood flow to 194% of control (same increase as in intact animals, carotid baroreceptor-denervated animals, and vagotomized animals) and produced equal reductions in cerebral vascular resistance (to 34% of control). These data show that the carotid and aortic chemoreceptors are not necessary for the increase in cerebral blood flow provoked by hypoxemia and that this response is not modified by the carotid and aortic baroreceptors.

Vagal and sinoaortic reflexes in postural control of circulation and renin release

Anesthetized cats were subjected to two 10-min trials of head-up tilting spaced 60 min apart. Bilateral cervical vagotomy, performed after the first tilting episode, did not affect the hemodynamic response to the change in posture, but significantyly and markedly reduced the increase in renin release from the innervated kidney. After sinoaortic denervation a marked and sustained arterial hypotension occurred during tilting, and the postural increase in renin release, though still limited to the innervated kidney, was even greater. When pressure homeostasis to tilting was disturbed, the renin release response was seen to be independent of the vagi, as it occurred after combined vagotomy and sinoaortic denervation. Maintenance of arterial pressure during tilting is mainly due to sinoaortic reflexes, whereas vagal reflexes are mostly responsible for the postural increase in renin release. The vagally independent release of renin observed when the cardiovascular response to tilting is impaired, is probably due to a direct action of arterial hypotension on intrarenal receptors, an action occurring only in innervated kidneys.

Selective surgery for chronic gastric and duodenal ulcers

At the University of Niigata Hospital, selection is attempted from several possible operative procedures for gastric and duodenal ulcers, the independent variables being the patients age, the acidity of gastric juice, the location of ulcer, the degree of gastric tonicity and the complicating lesions of stomach including gastritis. Each procedure and its indication are delineated as follows: 1) Usually, antrectomy or hemigastrectomy with vagotomy is performed for duodenal and gastric ulcers located distal to gastric angle, while a 75% gastrectomy is employed for the patients of old age or with a remarkable atony of the stomach. 2) For gastric ulcers located proximal to gastric angle, a 75% gastrectomy has been performed. 3) For high gastric ulcers, a segmental gastrectomy with pyloroplasty of the Heineke-Mikulicz type and vagotomy is employed. Upon performance of this procedure, the combined vagotomy is not carried out for the cases with the maximal free free acid of less than 30 to 40 cl.u., because the sufficient effective reduction of gastric acidity may be obtained by this procedure (less than 50% gastrectomy) alone. 4) For ulcers of cardiac region, a proximal gastrectomy, about 50% resection of the stomach, is performed. For the cases not associated with the conditions above mentioned, however, a 75% gastric resection is performed. These surgical procedures have been carried out in 659 cases with chronic peptic ulceration of the stomach and duodenum at the University of Niigata Hospital during the past 8 years. Conservative gastrectomies (antrectomy or hemigastrectomy with vagotomy, segmental gastrectomy and proximal gas t rectomy)have been performed in 189 cases or 29% of these 659 cases and gained satisfactory results. The present study has shown the procedures of selective surgery based on Prof. Sakai's new device at the University of Niigata Hospital. Detailed results of this policy may be reported in the future.