Acid Perfusion Research Articles

The supersensitive hypertensive lower esophageal sphincter. Precipitation of pain by small doses of intravenous pentagastrin.

The clinical and investigative features of eight patients with attacks of epigastric pain believed due to a hypertensive lower esophageal sphincter (LES) are described. Radionuclide esophageal transit studies were normal in all but one patient. Two patients had positive acid perfusion studies. Only three had an abnormal baseline esophageal manometry, but after small intravenous doses of pentagastrin all subjects experienced their presenting pain coincident with increases in LES pressure ranging from 75 to 140 mmHg. Five patients eventually required surgical myotomy of the LES, but pain relief which was immediate and complete in all proved permanent in only one. Two of the operated patients continued to experience severe attacks of pain refractory to medical therapy. The diagnosis of a hypertensive LES is best made by pentagastrin stimulation of the sphincter, but cutting the sphincter may not cure the patient.

Biological behaviour of Pu administered to animals as Pu-standard LICAM(C) complex: therapeutical attempts to decrease Pu kidney burden.

The biological fate of plutonium (Pu) introduced as a Pu-standard LICAM(C) complex was investigated in male rats of two strains, in male and female mice and in the baboon. We observed that, whatever the animal species or the entry route, this complex was deposited rapidly in the kidney. In addition, more of the complex accumulated in the rat (16% of injected radioactivity) than in either the mouse (7%) or baboon (5%). This Pu deposit was cleared spontaneously with a half-life of 10 days in the rat and only 5 days in the mouse. We noted that the complex was deposited on bone during this period and that, 10 days after the introduction of Pu, the skeleton became the main organ of retention of Pu (7% of the dose in the rat, 4% in mice and 3% in the baboon). In spite of this, which would indicate that Pu-standard LICAM(C) resembles a weak complex, gut transfer was comparable with that of a strong complex 1.10(-3) (f1 = 1.10(-3)). Pu deposit seemed to be pH dependent and could be modified be varying the pH balance of urine. Bicarbonate was among the most effective of the different drugs used to affect this balance, as 5 h of continuous perfusion decreased the kidney Pu burden by a factor of 4. Such efficacy was also observed with diethylenetriaminepenta-acetic acid (DTPA) perfusion. The pragmatic consequence of these experiments is the recommendation of mixed therapy: standard LICAM(C) plus bicarbonate or DTPA.

Oesophageal function and symptoms in moderate and severe asthma.

Fifty-five children and adolescents, 8 to 19 years of age, with moderate or severe asthma, and 28 healthy volunteers, 11 to 16 years of age, were interviewed about oesophageal and bronchial symptoms and investigated with oesophageal manometry combined with pH-reflux tests, an acid perfusion test and an acid clearing test. Oesophageal dysfunction (OD) was significantly more common in asthmatic (60%) than in healthy (14%) subjects (p less than 0.01). Ten of 18 subjects (56%) with frequent nocturnal or morning asthma had a positive acid perfusion test as compared to 16% of patients with less severe asthma (p less than 0.01). Non-allergic asthma was not significantly more related to OD than was allergic asthma. Presence of OD was not related to present beta 2-stimulant or theophylline medication. Symptoms of OD had a sensitivity of 52% and a specificity of 100% regarding OD in the asthmatic subjects. In conclusion, asthma was frequently associated with OD. There is indirect evidence that OD, especially acid hypersensitivity of the oesophagus, can aggravate asthma.

Systematic Esophageal Evaluation of Patients With Noncardiac Chest Pain

We prospectively studied 73 patients with angina-like chest pain severe enough to warrant admission to a coronary care unit over a five-month period. Thirty-four patients (47%) were found to have coronary artery disease as the cause of their symptoms, based on exercise testing, stress radionuclide imaging, or cardiac catheterization. The remaining 39 patients had normal cardiac findings and then underwent videoesophagography, radionuclide esophageal transit study, and esophageal manometry. Thirty-three of the 39 underwent acid perfusion testing (modified Bernstein's test). The findings at esophageal manometry were abnormal in 29 (74%) of 39. Manometric diagnoses were "nutcracker esophagus" in 17 (59%), nonspecific esophageal motility disorders in nine (31%), diffuse esophageal spasm in two (7%), and achalasia in one (3%). Bernstein's test reproduced symptoms in only 12%. The sensitivity of videoesophagography in detecting esophageal motility disorders was 66%, and that of radionuclide esophageal transit was 79%. The positive predictive values were 86% and 85%, respectively.

The Effect of Acid and Bethanechol Stimulation in Patients with Symptomatic Hypertensive Peristaltic (Nutcracker) Esophagus Evidence That This Disorder May Be a Precursor of Diffuse Esophageal Spasm

The hypertensive peristaltic (nutcracker) esophagus represents a motility disorder characterized clinically by squeezing retrosternal chest pain and manometrically by high amplitude esophageal peristaltic contractions. This study was designed to examine whether the nutcracker esophagus is: (a) a distinct entity, (b) a member of the spectrum of primary esophageal dysmotilities (e.g., diffuse esophageal spasm and achalasia), or (c) is secondary to reflux-induced acid sensitivity. Thirteen patients with a nutcracker esophagus by baseline manometry were subsequently studied after acid perfusion and bethanechol stimulation (0.08 mg/kg). Records were analyzed for symptomatic response and motility changes. Eight of 13 (62%) experienced chest pain during acid perfusion, but none had significant motility changes documented during this period. After bethanechol injection, chest pain occurred in six of 12 (50%) patients; two had burning pain and in the other four (33%) their squeezing chest pain was reproduced. Changes in the motility tracing with evidence of disordered motility suggestive of diffuse esophageal spasm were seen after bethanechol in seven of the 12 tracings analyzed (58%), including all six patients who developed chest pain. We conclude that patients with nutcracker esophagus on baseline manometry may develop motility patterns consistent with diffuse esophageal spasm after provocation with bethanechol. We take this to suggest that the nutcracker esophagus is part of the continuum of primary motility disorders and may actually be a precursor of diffuse esophageal spasm.

Feedback regulation of pancreatic enzyme secretion. Suppression of cholecystokinin release by trypsin.

Feedback regulation of pancreatic enzyme secretion occurs in rats. Whether such a system exists in man remains unsettled and the responsible mechanism is unknown. To investigate this question gastrointestinal intubation and perfusion were performed in 12 healthy subjects. Intraduodenal perfusion of trypsin-inhibited phenylalanine-, oleic acid-, and meal-stimulated chymotrypsin and lipase outputs in a dose-related manner. The minimal concentration of bovine trypsin needed to inhibit pancreatic enzyme secretion was 0.5 g/liter. 1 g/liter caused a maximal suppression of 35 +/- 4% of the phenylalanine-stimulated chymotrypsin release. This inhibitory effect was protease-specific. Intraduodenal perfusion of phenylalanine and oleic acid increased plasma cholecystokinin (CCK) from a basal level of 0.9 +/- 0.06 to 5.3 +/- 0.9 pM and 7.2 +/- 1.3 pM, respectively. Addition of bovine trypsin to the perfusates significantly reduced the plasma CCK level to basal values. This inhibitory effect of trypsin on CCK release was dose dependent and specific to proteases. Therefore, the present studies indicate that feedback regulation of pancreatic enzyme secretion is operative in man and it is mediated by release of CCK.

Experimental esophagitis in a rabbit model. Clinical relevance.

Esophagitis occurs in patients with excessive acid and/or alkaline gastroesophageal reflux. This observation prompted us to develop a continuously perfused in vivo rabbit esophageal model to examine the potential for different endogenous injurious agents to cause H+ back diffusion and morphologic evidence of esophagitis. We found that HCl at physiologic pH values did not break the mucosal barrier to H+ back diffusion or cause esophagitis. Bile salts at physiologic concentrations in both an acid or alkaline perfusate broke the mucosal barrier and caused H+ back diffusion, but failed to cause a morphologic injury consistent with clinical reflux esophagitis. Instead, proteolytic enzymes, such as pepsin in an acid environment and trypsin in an alkaline environment, caused a severe hemorrhagic erosive esophagitis consistent with that seen clinically. We feel new therapeutic strategies for the treatment of reflux esophagitis should be directed at proteolytic enzymes rather than only HCl or bile salts. Finally, we showed sucralfate to be a mucosal protectant against the acid-pepsin injury.

24-Hour recording of esophageal pressure and pH in patients with noncardiac chest pain

Sixty patients with anginalike chest pain of noncardiac origin were studied to determine the diagnostic value of 24-h ambulatory esophageal pH and pressure monitoring. The results of these 24-h studies were compared with those obtained by established methods, including x-rays, endoscopy with biopsy, conventional esophageal manometry, and acid perfusion test. Esophageal origin of the chest pain was considered to be likely if the familiar pain sensation was reproduced by the acid perfusion test, or if the pain occurred during an episode of gastroesophageal reflux, severe motor disorders, or both. When the results of established methods were combined and interpreted according to predetermined criteria, esophageal origin of the pain was shown to be likely in 27% of the patients. The 24-h recordings, alone, showed the esophagus to be the likely cause of the pain in 35% of the patients. Combination of all conventional examinations and of 24-h recordings made esophageal origin of the pain likely in 48% of the patients.

Gall stone disease without gall stones--bile acid and bile lipid metabolism after complete gall stone dissolution.

Although bile acid and bile lipid metabolism have been studied in established cholelithiasis, little is known about them in patients destined to develop gall stones, but in whom the stones have not yet appeared (prestone gall stone disease). After confirmed complete gall stone dissolution and withdrawal of treatment, gall stones recur frequently. Before the stones reappear, these patients have 'poststone gall stone disease'. In 13 such patients we confirmed complete gall stone dissolution with two normal cholecystograms and in 11 of the 13 by normal ultrasonography, measured bile acid and bile lipid composition in fasting duodenal bile, bile acid synthesis from marker corrected three day faecal bile acid excretion, bile acid pool size using an abbreviated isotope dilution technique, 'steady-state' bile lipid secretion using a duodenal amino acid perfusion system and then calculated the enterohepatic cycling frequency of the bile acid pool and the relationship between pool size and body weight. The results confirm that after withdrawal of treatment the biliary cholesterol saturation index reverts to levels (1.6 +/- SEM 0.4) comparable with those before dissolution therapy first began (1.6 +/- 0.2; NS). The mean bile acid pool size in the 13 patients of 4.4 +/- 0.5 mmol was comparable with that in untreated gall stone patients. Pool size was significantly smaller in the nine non-obese patients (3.5 +/- 0.3), than in the four obese (6.0 +/- 0.8; p less than 0.05). It also correlated significantly with body weight (r = 0.72) and with %IBW (r = 0.79). The coefficients of variation for biliary bile acid, phospholipid and cholesterol secretion were high, but the mean hourly secretion rates were of the same order as those seen in untreated gall stone patients studied with the amino acid duodenal perfusion stimulus. These results provide a baseline for assessing the response to postdissolution treatment and may indicate metabolic events leading to gall stone formation.

Follow-up of Patients With Esophageal Angina

To the Editor.— Esophageal pain is an increasingly well-recognized mimic of angina, and patients are often discharged from follow-up if the esophagus rather than the heart is the cause of symptoms. Since little is known about the long-term prognosis of this group, we traced 16 patients who were initially seen four years earlier in an emergency room setting, for reasons of anginalike pain due to esophageal disease.1 Report of a Study— The study group included seven males and nine females; average age at presentation was 50 years. Investigations had shown that esophageal disease was the definite cause of pain in eight patients (definite pain was defined as a positive provocation test result using acid perfusion or intravenous ergonovine maleate injection, or the development of esophageal spasm during spontaneous pain), and the probable cause of pain in eight others (probable pain was defined as two independent abnormalities of esophageal function). All

Esophageal Blood Flow in the Cat: Normal Distribution and Effects of Acid Perfusion

The radioactive microsphere technique was used to estimate blood flow to different regions of the esophagus and to adjacent regions of the stomach before and after perfusion of the esophagus with hydrochloric acid (pH 1.5) for 5 min. Under resting conditions total blood flow, as well as blood flow to the mucosal-submucosal layer and the muscular layer, to both sphincters was significantly higher than to the esophageal body. Blood flow to the adjacent regions of the stomach was significantly higher than esophageal blood flow. Acid perfusion resulted in a large increase in total blood flow in both sphincters and the lower esophageal body. Gastric blood flow was not altered by acid perfusion. The esophageal hyperemia resulted primarily from an increase in blood flow to the muscular layer; mucosal-submucosal blood flow was increased only in the lower esophageal sphincter. The present study indicates that short periods (5 min) of gastroesophageal reflux may increase esophageal blood flow.

Esophageal function, radiography, and dysphagia in Sjögren's syndrome.

Esophageal function and anatomy were investigated with manometry, acid perfusion test, acid clearing test, and x-ray in 11 patients with primary Sjögren's syndrome (SS) and in 11 with secondary SS. The manometric investigation revealed minor motor differences in the SS patients as compared to 16 controls, ie, shorter peristaltic contraction time of the whole esophagus, and faster peristaltic velocity preferably in the distal part of the esophagus, while the results from the reflux tests did not differ between patients and controls. Radiographic examination revealed upper esophageal webs in 10% (2/20), and hiatal hernia in 25% (5/20). The dysphagia as reported by 73% of the patients cannot be explained by webs or impaired motor function and is regarded to be secondary to lack of saliva, making the solid bolus passage difficult.

Hiatus hernia in gastroesophageal reflux disease.

Upper gastrointestinal endoscopy and radiologic examination were performed in 101 patients with symptoms strongly suggestive of gastroesophageal reflux (GER) disease. Hiatus hernia (HH) was found in 50 patients diagnosed by radiography or endoscopy, or both, in 22, 19, and 9 patients respectively. Severe endoscopic esophagitis (grades III and IV) was found more often (p less than 0.05) in the patients with HH than in those without. The same was true for the early positive timed acid perfusion tests (p less than 0.02). Furthermore, the patients with HH more often had reflux by the standard acid reflux test (42 of 50 versus 28 of 51; p less than 0.01), gastroesophageal scintigraphy (47 of 50 versus 40 of 51; p less than 0.05), and radiography (20 of 50 versus 2 of 51; p less than 0.001) than the patients without HH. The results show that severe GER disease can occur without an associated HH and indicate that patients with symptoms of GER disease and associated HH are likely to have a more severe GER disease than those without HH.

Surgical management of the failed gastroplasty

Gastroplasty has been used in surgical management of reflux for 25 years. The creation of a gastric tube before fundoplication complicates further corrective procedures should the original operation fail. Experience has been gained with 51 patients, 34 having partial fundoplication gastroplasty and 17 having total fundoplication, who have had major persistent or recurrent symptoms. All were evaluated by history, radiology, endoscopy, manometry with pH, and acid perfusion testing before surgical management. The patients undergoing partial fundoplication gastroplasty had heartburn (85.3%), reflux (70.6%), and dysphagia (94.1%). Radiologic recurrence was present in 26.5%, endoscopic incompetence in 94.1%, and a stricture in 26.5%. The patients who had a total fundoplication gastroplasty had heartburn (52.9%), reflux (29.4%), and dysphagia (82.4%). Radiologic recurrence was present in 29.4%, endoscopic incompetence in 35.3%, and a stricture in 5.9%. On average, these patients had had 2.3 prior operations (range one to five operations). The dominant cause of failure (in the absence of anatomic recurrence) with partial fundoplication gastroplasty was continued or recurrent reflux and with total fundoplication gastroplasty, too tight or too long a fundoplication. All patients had a thoracoabdominal revision total fundoplication gastroplasty and a 1 cm completion fundoplication. Pyloromyotomy was added if not previously performed. There were no deaths or major morbidity. Follow-up in 51 patients averages 4.2 years (range 0.3 to 8.8 years). None has radiologic recurrence, one has minor reflux, one a traumatic diverticulum, and one has moderate esophageal obstruction. Of these patients, 82.4% are asymptomatic, 13.7% have minor symptoms, and 3.9% (two patients) have significant residual symptoms. This conservative surgical approach avoids the higher mortality of resection with interposition and provides satisfactory results.

Oesophagitis, signs of reflux, and gastric acid secretion in patients with symptoms of gastro-oesophageal reflux disease.

In a study comprising 100 patients referred to a surgical clinic with symptoms suggestive of gastro-oesophageal reflux disease the value of different diagnostic procedures was investigated. Positive acid perfusion and 24-h pH tests were the commonest findings. Forty-nine per cent showed a normal oesophageal mucosa or diffuse oesophagitis at endoscopy. The severity of heartburn and regurgitation did not differ between patients with normal oesophageal mucosa and oesophagitis of various severities. The severity of macroscopic oesophagitis was significantly correlated to the total reflux time, the presence of reflux or a hiatal hernia at radiology, an open cardia or reflux at endoscopy, pressure transmission or reflux and low lower oesophageal sphincter pressure at manometry. Gastric hypersecretion was found in 66% of the patients. Gastric acid secretion was not correlated to the severity of oesophagitis or to the findings at 24-h pH test. In patients with severe oesophagitis the sensitivity for radiologic, manometric, and endoscopic signs of incompetence of the gastro-oesophageal junction was 94%.

Maintenance Treatment with Ranitidine Compared with Fundoplication in Gastro-oesophageal Reflux Disease

The study comprises 31 patients with gastro-oesophageal reflux disease who received 8 weeks' treatment with ranitidine. Sixteen of the patients received in addition maintenance treatment with ranitidine (150 mg twice daily) for another 6 months, and fundoplication was performed on 15 patients. There was a significant improvement in endoscopic and histologic findings, a decrease in gastric acid secretion, and a reduction of symptoms during short-term treatment with ranitidine. No further improvement was seen in any of the factors after half a year of ranitidine. After surgery the total reflux time during 24 h decreased to practically zero, all patients had normal endoscopic findings and negative acid perfusion tests, and reflux symptoms had disappeared completely. Anti-reflux surgery was superior to treatment with ranitidine. Reflux oesophagitis is therefore not improved any further by a half year's treatment with ranitidine beyond what is achieved with short-term therapy.

Chenodeoxycholic and ursodeoxycholic acids alter motility and fluid transit in the canine ileum.

We examined the effects of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) on fasting motility patterns and transit in ileocolonic loops of 5 dogs. Animals were prepared with isolated loops (40 cm ileum and 5 cm colon) which maintained neuromuscular continuity with the intact bowel through a bridge of tunica muscularis. Myoelectrical activity was recorded from multiple serosal, monopolar electrodes and muscle contractions recorded from serosal strain gauges; fluid transit was assessed by continuous perfusion (1.4 ml min-1) of solutions containing polyethylene glycol 4000 marker, with or without bile acids. Saline perfusion did not disturb the fasting cycle of motility and mean cycle length in unperfused (106 +/- 7 min) loop was the same as during perfusion of saline (108 +/- 9 min). Bile acids abolished interdigestive cycles in 11 of 12 experiments, fasting patterns returned 64-106 min after bile acid perfusion was stopped. The fasting pattern continued to cycle normally in the proximal small bowel during bile acid perfusion. CDCA (15 mM) stimulated the occurrence of propulsive contractions of long duration. Bile acids shortened transit time through the loops and altered the pattern of flow towards a more continuous, steady stream. These effects of bile acids on ileal motility, like those described previously in the colon, could play a role in bile acid diarrhea.

Intraluminal pH and oesophageal motility in patients with gastro-oesophageal reflux.

The effect of intraluminal pH on motor activity of the lower oesophageal body was studied in patients with pathological gastro-oesophageal reflux. Liquid boluses with a pH range of 6.98-1.1, infused in the distal oesophagus of 21 patients during manometric recording of motor activity, elicited either secondary peristalsis or simultaneous contractions. Acid pH did not affect the threshold of distension required to elicit secondary peristalsis. Oesophageal responses to volumes of instillate did not differ in patients with normal and abnormal acid clearing test, nor in patients with a negative and positive acid perfusion test.

The acid perfusion test in gastroesophageal reflux disease.

An acid perfusion test, isotope scanning, endoscopy, and esophageal biopsy were performed in 101 patients with symptoms strongly suggestive of gastroesophageal reflux (GER) disease. A positive acid perfusion test within 30 min (APT) and within 5 min (TAPT) was found in 70.2% and 37.6% of the patients, respectively. A positive APT was found significantly more often in patients with than without endoscopic esophagitis, whereas a positive TAPT was found significantly more often in patients with severe symptoms than in patients with moderate symptoms and in a significantly higher proportion of patients with than without GER by scintigraphy. Neither the APT nor the TAPT showed any dependency on the presence of histologic esophagitis. Most (97%) patients with a negative acid perfusion test, in addition to typical symptoms, also presented with scintigraphic, endoscopic, or histologic evidence of GER disease. Although it shows that the acid perfusion test, particularly when early positive, may serve as a weak predictor of the severity of GER disease, the present study gives little support to the test's clinical usefulness.

Regional distribution and release of peptide YY with fatty acids of different chain length.

The present study examines peptide YY responses to regional intestinal perfusion of fatty acids of different chain length--dodecanoate and oleate. Six dogs with chronic gastric, duodenal, and jejunal fistulas were studied. Proximal perfusates were administered into the duodenum and diverted through an intestinal fistula placed 45 cm beyond the duodenal cannula. Distal perfusates were administered into the caudal stoma of this intestinal stoma. Peptide YY responses to proximal, distal, and whole-gut perfusion were compared. Proximal perfusion with oleate or dodecanoate failed to release peptide YY. In contrast, distal and whole-gut perfusion with either fatty acid produced significant increases that were of similar magnitude. Immunocytochemical studies demonstrated that peptide YY cells predominated in the canine ileocolonic mucosa and decreased progressively in an orad direction. We conclude that peptide YY release is not dependent on fatty acid chain length and that the duodenum does not play a dominant role in peptide YY release. As such, peptide YY release differs from that of its cousin pancreatic polypeptide and may result at least in part from direct stimulation of the peptide YY cell in the ileocolonic mucosa.