Acid Perfusion Research Articles

Colonic motor activity in acute colitis in conscious dogs

The changes in motor activity of the colon during acute colitis were investigated in six conscious dogs. The motor activity was recorded with seven straingauge transducers. Colitis was induced in the entire colon by luminal perfusion of acetic acid. The dogs exhibited urgency and diarrhea with mucus and blood during colitis. The mucosa was diffusely erythematous and friable and there were scattered ulcerations over the mucosal surface. The motor activity of the colon changed in several ways during colitis: (a) the total duration per hour and the mean duration of contractile states decreased significantly; (b) the cycle length of colonic migrating motor complexes was significantly prolonged, and the nonmigrating motor complexes were almost completely absent; and (d) the incidence of giant migrating contractions increased significantly. About half of the giant migrating contractions were followed by defecation. The remaining expelled mucus or gas. Sometimes, a migrating motor complex in the colon was also followed by defecation; this was never observed in the normal state. The motor activity of the colon was still decreased and the cycle length prolonged 21 days after induction of colitis. However, the dogs were asymptomatic at this time and the mucosa looked normal at colonoscopy. The incidence of giant migrating contractions was also normal at this time. It was concluded that the dog is a good model for the study of colitis because of the similarity of symptoms with human ulcerative colitis. The phasic contractions of the colon decreases during colitis but the incidence of giant migrating contractions is increased. The diarrhea in colitis may primarily be due to the large number of giant migrating contractions in the middle and the distal colon.

Role of blood flow and alkaline secretion in acid-induced deep duodenal villous injury in rats

The effect of 16,16-dimethylprostaglandin E2 (dmPGE2) and corticotropin-releasing factor (CRF) on duodenal blood flow, alkaline secretion, and acid-induced deep duodenal villous injury was studied. The duodena of anesthetized rats were prepared for simultaneous measurement of alkaline secretion by back titration, and blood flow by hydrogen gas clearance; or for perfusion with 0.1 N HCl and histological examination of villous injury. The results revealed that the dmPGE2-induced increase in basal alkaline secretion (due solely to an increase in the volume of secretion) appears to be a better predictor of protection against exogenous acid-induced deep duodenal villous injury than rise in duodenal blood flow, since CRF induces a similar rise in duodenal blood flow but does not enhance alkaline secretion or reduce acid-induced villous damage. The absence of a greater loss of H+ during acid perfusion of the duodenum in the dmPGE2-treated rats, however, suggests that the mechanism of the dmPGE2 protection against acid-induced deep duodenal villous injury cannot be explained entirely by its ability to increase basal duodenal alkaline secretion.

Prospective study on prevalence of esophageal chest pain in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia

The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram.

Symptomatic gastro-oesophageal reflux, abnormal oesophageal acid exposure, and mucosal acid sensitivity are three separate, though related, aspects of gastro-oesophageal reflux disease.

The Bernstein test has been used as a test of oesophageal acid sensitivity for over 30 years but its clinical value has been challenged by the advent of ambulatory pH monitoring. Furthermore, the relation between mucosal acid sensitivity, symptomatic reflux, and abnormal oesophageal acid exposure time is unclear. This study examined the relation between these three parameters in patients referred for pH monitoring with unexplained chest pain or heartburn. Fifty consecutive patients were studied - nine with non-cardiac chest pain and 41 with a history of heartburn. Symptomatic reflux was defined as a greater than or equal to 50% temporal association between pain episodes and reflux events (pH less than 4) during pH monitoring. A positive acid perfusion test (in which the patient's usual symptoms were evoked by acid, though not saline) had a 100% sensitivity, 73% specificity, and 81% accuracy for the detection of symptomatic reflux. All 10 patients with symptomatic reflux during pH monitoring had evidence of mucosal acid sensitivity. A negative acid perfusion test made symptomatic reflux unlikely. However, symptomatic reflux or a positive acid perfusion test, or both, were found in some patients with a normal oesophageal acid exposure time during pH monitoring. Mucosal acid sensitivity, abnormal oesophageal acid exposure time, and symptomatic reflux should be regarded as separate, though related aspects of reflux disease. The Bernstein test is simple, safe, and easily performed. A positive test helps to identify an oesophageal cause of symptoms, particularly in patients in whom other aspects of 'gastro-oesophageal reflux disease' are absent, or who do not have symptoms during pH monitoring.

Esophageal Manometry with Provocative Testing in Patients with Noncardiac Angina-Like Chest Pain

In a five year period 238 of 594 esophageal manometric studies performed in the authors’ laboratory were done on patients whose major reason for referral was noncardiac angina-like chest pain. Standard eophageal manometry was performed followed by an acid-antacid perfusion period (Bernstein test) and then subcutaneous bethanechol (80 μg/kg to a maximum of 5 mg) was adminstered. Baseline manometry was normal in 38% of patients and was diagnostic of ‘nutcracker’ esophagus, nonspecific esophageal motility disorder, diffuse esophageal spasm and isolated hypertensive lower esophageal sphincter in 24%, 19%, 16% and 3% of patients, respectively. Ninety-six of 238 patients (40%) experienced reproduction of their presenting angina-like chest pain during acid perfusion. In 80% of these patients there were associated esophageal motor abnormal ilies induced by the acid perfusion. Thirty-six of 212 (17%) experienced pain reproduction following the injection of bethanechol; however, 16 of these had already had their presenting chest pain reproduced during the acid perfusion study. In two-thirds of the patients with pain reproduction following bechanechol there was an associated bethanechol-induced esophageal motility disorder. Overall 49% of patients had their pain reproduced during provocative testing. The acid perfusion test reproduced the pain much more frequently than bethanechol simulation. This study reaffirms the value of esophageal manometry and provocative testing in this group of patients.

Twenty-four-hour esophageal pH monitoring: The most useful test for evaluating noncardiac chest pain

study objective: To compare the diagnostic capabilities of traditional esophageal tests (manometry and provocative testing with acid and edrophonium) and 24-hour esophageal pH monitoring in identifying an esophageal cause of chest pain. design: A prospective study of 100 consecutive patients referred by cardiologists to the esophageal laboratory for evaluation of esophageal causes of chest pain. setting: Tertiary-referral university hospital. METHODS: Esophageal manometry performed with 10 wet swallows of water. Acid perfusion (0.1 N hydrochloric acid) and edrophonium (80 μg/kg intravenously) tests were placebo-controlled with a positive study defined as replication of typical chest pain. Esophageal pH monitoring identified (1) abnormal acid exposure times in the upright, supine, or combined position, and (2) correlation between symptoms and acid reflux, i.e., symptom index. The esophagus was identified as “probably” contributing to chest pain only if the acid or edrophonium test was positive or if there was a positive correlation between symptoms and acid reflux during pH monitoring. results: Esophageal manometry was abnormal in 32 patients (32%), but patients were asymptomatic during the study. The acid perfusion test was positive in 18 of 95 patients (19%), and the edrophonium test was positive in 15 of 78 patients (19%). Abnormal acid exposure times were found in 48 patients (48%). Of the 83 patients with spontaneous chest pain during 24hour pH testing, 37 patients (46%) had abnormal reflux parameters and 50 patients (60%) had a positive symptom index (mean positive score 56%, range 6% to 100%). conclusions: Acid reflux is a common and potentially treatable cause of noncardiac chest pain. Traditional esophageal tests usually miss this diagnosis. Twenty-four-hour esophageal pH monitoring with symptom correlation is the single best test for evaluating patients with noncardiac chest pain.

Quinolinic acid: Effect on 45Ca content in perfused rat heart preparations and its calcium ion binding property in Krebs-Henseleit medium and blood serum

In the experiment it was found that quinolinic acid perfusion was accompanied with the increase in calcium 45Ca content in myocardium tissue. The increase in calcium content was associated with a decrease in heart contractility. Moreover, it was shown that quinolinic acid can form complexes with calcium ions in Krebs-Henseleit medium as well as in blood serum but only to a small degree.

Gastro-Oesophageal Reflux and Severity of Pulmonary Disease in Cystic Fibrosis

The correlation between oesophageal dysfunction (OD), pathologic gastro-oesophageal reflux (GOR), and severity of pulmonary disease was studied in 12 patients with cystic fibrosis (CF). They were interviewed about symptoms of OD and underwent 24-h pH recording in the oesophagus, oesophageal manometry combined with reflux provocation tests, the acid perfusion test, the acid clearance test, lung function tests, and scoring of the chest radiograph. Six of the 12 patients reported symptoms of OD. Abnormal GOR, as shown by 24-h pH monitoring of the oesophagus, was found in eight of them. Altogether 9 of the 12 participants had at least one pathologic oesophagus test result. Results of radiologic examinations of the oesophagus, performed in six patients, were pathologic. The four patients with the best chest radiograph scores and the best lung function had significantly less signs and symptoms of OD and GOR than the other eight patients. We conclude that OD, GOR, and pulmonary disease covariate in CF.

Mechanism of acid-induced release of secretin in rats. Presence of a secretin-releasing peptide.

In fasting rats, intraduodenal infusion of dilute hydrochloric acid results in significant increases in both pancreatic exocrine secretion and plasma concentration of secretin. To test the hypothesis that acid-induced release of secretin is mediated by a secretin-releasing factor (S-RF), anesthetized rats were prepared with pyloric ligation, duodenal and jejunal cannulas, and pancreatic duct cannulas. Donor rats were infused intraduodenally with 0.01 N HCl, 0.15 M NaCl, or a combination of 0.01 N HCl and 0.05 N NaHCO3 at 0.3 ml/min for 1.5 h, and the perfusates were collected via jejunal cannulas. The perfusates with pH adjusted to 6.0 were concentrated threefold and infused into the duodena of recipient rats. The concentrate of acid perfusate (CAP) significantly increased both pancreatic volume flow and bicarbonate output and plasma concentration of secretin, whereas concentrates of the saline perfusate (CSP) or the perfusate of a combination of 0.01 N HCl and 0.05 N NaHCO3 (CABP) did not influence pancreatic secretion or plasma concentration of secretin. The increased pancreatic secretion by CAP was attributed to increased circulating secretin because when secretin was immunoneutralized by a rabbit antisecretin serum, CAP-stimulated pancreatic secretion was abolished. The bioactivity of CAP was trypsin-sensitive and heat stable. The active substance in CAP had a molecular weight of less than 5,000 and greater than 1,000, as determined by ultrafiltration and bioassay. In conclusion, dilute HCl releases an S-RF into the upper small intestinal lumen to stimulate release of secretin. This substance, with molecular weight of less than 5,000, is heat stable and trypsin sensitive. Thus, the acid-stimulated release of secretin is mediated by a secretin-releasing peptide in the upper small intestinal lumen.

Mechansims mediating inhibition of gastric motility in response to duodenal acid perfusion in rats

Mechansims mediating inhibition of gastric motility in response to duodenal acid perfusion in rats

Esophageal Contribution to Chest Pain in Patients with Coronary Artery Disease

We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty-two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients.

Ancillary Tests in the Diagnosis of Gastroesophageal Reflux Disease

This article reviews some of the diagnostic procedures for gastroesophageal reflux disease other than the procedures of choice, endoscopy and prolonged intraesophageal pH monitoring. The author discusses the roles of the acid perfusion (Bernstein) test, radiology, manometry, and radionuclide scintigraphy in the diagnosis and management of gastroesophageal reflux disease.

Arrested exocytosis of atrial secretory granules

Release of atrial natriuretic peptide (ANP) from atrial muscle cells is thought to occur by exocytosis of secretory granules, as in other secretory systems. However, in the atrial myocyte, exocytosis has previously proved difficult to detect ultrastructurally. In order to study the mechanism of ANP release and related events, we have applied two separate techniques—tannic acid perfusion and ultrarapid freezing—specificially designed to arrest exocytosis. An increased number of fusion sites was found after ultrathin sectioning and freeze-fracture of tannic acid-treated atria enabling a hypothetical release sequence to be constructed. Detail of granule substructure was also obtained, suggesting the presence of a coat to the secretory granule core. Ultrarapid freezing, followed by freeze-fracture and freeze substitution, has confirmed aspects of the proposed exocytotic sequence, suggesting that this release is not due to the application of tannic acid, and these techniques also produced further evidence for the existence of the granule-core coat. Coated pits and vesicles were also found in large numbers in tannic acid-treated atria and interactions between coated vesicles and secretory granules were visualized. The possible role of coated vesicles in an exocytotic/endocytotic membrane retrieval pathway is discussed.

Ambulatory 24 hour intraoesophageal pH and pressure recordings v provocation tests in the diagnosis of chest pain of oesophageal origin.

Fifty patients with non-cardiac chest pain underwent 24 hour intraoesophageal pH and pressure recording and provocation tests to determine the relative value of both techniques in establishing the oesophageal origin of the chest pain. Twenty six patients (52%) had at least one positive provocation test: the acid perfusion test was positive related in 18 patients (36%), the edrophonium test in 16 patients (32%), the vasopressin test in five patients (10%), and the balloon distension test (performed in only 20 patients) in one (5%). The 24 hour pH and pressure recording correlated spontaneous chest pain attacks with abnormal motility or gastro-oesophageal reflux in 19 patients (38%). Fourteen of these patients also had at least one positive provocation test. Therefore, 24 hour pH and pressure recordings are only slightly better than a set of provocation tests in identifying the oesophagus as the cause of chest pain (10% diagnostic gain). In the case of oesophageal chest pain, however, 24 hour recording appeared to be the only way to identify the nature of the underlying oesophageal abnormality that caused the spontaneous pain attacks--for example, gastro-oesophageal reflux, motility disorders, or irritability of the oesophagus.

Blood pressure measurement in adults: large cuffs for all?

The aim of the study was to determine whether a single size of cuff for adult blood pressure measurements is appropriate for general clinical practice. The study was a prospective survey of a sample of adult blood pressure measurements using two cuffs with different bladder sizes (12 X 23 cm and 15 X 33 cm) in a randomised design using a random zero sphygmomanometer. Blood pressures were measured in a general practice and in a hospital outpatient clinic. The participants were 35-60 year old men and women invited to attend a blood pressure screening programme in the general practice (n = 170), and 35-74 year old patients attending a general medical outpatients (n = 72). The small cuff gave higher readings of systolic blood pressure than the large cuff (mean difference 4.4 mm Hg). The difference increased as systolic pressure increased but did not show a clear association with arm circumference. The small cuff also gave higher diastolic pressure readings (mean difference 3.0 mm Hg), but only when arm circumference exceeded 30 cm. The variability of the differences between readings from the two cuffs was wide, little affected by arm circumference, and was similar to the variability between measurements using the same cuff size. In terms of precision there is no basis for using two different cuff sizes unless it is physically difficult to obtain a reading with one or the other. Since readings with large cuffs are closer to intraarterial pressures in large arms, and the large cuff used here did not underestimate diastolic pressure in small arms, the large cuff alone could be recommended for general use.

Effect of portal hypertension onIn Vivo bile acid-mediated small intestinal mucosal injury in the rat

This study's purpose was to determine whether portal hypertension adversely affects small intestinal mucosal injury. Portal hypertension was produced in male Sprague-Dawley rats by two-stage ligation of the portal vein. Sham-operated rats were used as controls. Two weeks later, intestinal injury was produced by in vivo perfusion with 5 mM chenodeoxycholic acid for 30 min. Intestinal injury was assessed by quantitative morphometry and by measuring intestinal water and mannitol absorption. Portal hypertension resulted in more injury in the distal perfused intestine as manifested by increased villus tip denudation [portal hypertensive 52.5 +/- 9.6 (SEM) vs controls 28.1 +/- 5.7 microns, P = 0.05). Additionally there was a significant decrease in the unperfused duodenal villus height in portal hypertensive rats (portal hypertensive 755 +/- 22 vs controls 848 +/- 28 microns, P less than 0.02). Portal hypertension had no significant effect on the increase in mannitol absorption or water secretion caused by chenodeoxycholic acid perfusion. This study suggests that portal hypertension alters small intestinal mucosa and increases susceptibility to injury.

The Prevalence of Abnormal Esophageal Test Results in Patients With Cardiovascular Disease and Unexplained Chest Pain

The purpose of our study was to assess the prevalence of esophageal test abnormalities in patients with known cardiovascular disease and persistent chest pain. We performed a retrospective review of symptoms, manometry, and provocative test results performed on patients with undiagnosed chest pain. The 220 patients with angiographically determined cardiac disease and persistent chest pain were divided into three groups: coronary artery disease (125 patients), mitral valve prolapse (38 patients), and coronary bypass/angioplasty (57 patients). A comparison group consisted of 159 patients with noncardiac chest pain. All patients underwent esophageal manometry and placebo-controlled provocative testing (acid perfusion test and edrophonium chloride test). The prevalence of esophageal motility disorders in the noncardiac chest pain group (27%) was similar to that in the coronary artery disease (24%), mitral valve prolapse (37%), and coronary bypass/angioplasty (30%) groups. The frequency of nutcracker esophagus (11% to 16%) and diffuse esophageal spasm (2% to 7%) was remarkably constant. The prevalence of any positive provocative result in the noncardiac chest pain group (27%) was similar to that in the coronary artery disease (19%), mitral valve prolapse (32%), and coronary bypass/angioplasty (20%) groups. Furthermore, completely negative results of esophageal investigation occurred in 55%, 62%, 42%, and 59% of the respective patient groups.

Prostaglandin E 2 formation by rat gastroduodenal tissue following intragastric acid perfusion

Rat gastroduodenal mucosa forms prostaglandin (PG) E 2. However, little is known about regional differences in PGE 2 formation or the effect of gastric hydrochloric acid (HCl) perfusion on regional PGE 2 formation. In this study, the rats were divided into 3 groups. Group 1 received intravenous (i.v.), 1 ml/h, and intragastric (i.g.), 8 ml/h, perfusions of saline simultaneously for 3 h. Group 2 received saline i.v. and 0.15 N HCl i.g., 8 ml/h. Group 3 was injected with a bolus of aspirin (ASA), 60 mg/kg, followed by ASA, 40 mg/kg/h i.v., and 0.15 N HCl i.g.. The gastric aspirates were analyzed for volume and pH. Segments of gastroduodenal tissue from the fundus, corpus, antrum, and duodenum were minced and then incubated in 1 ml of 50 mM Tris buffer, pH 8.4, for 30 sec with mixing; the incubate was assayed for PGE 2 by radioimmunoassay. Intragastric HCl decreased the pH of aspirate without producing gastric mucosal lesions. However, when combined with i.v. ASA, ulcer formation was present in all animals (p < 0.05). PGE 2 was formed by isolated tissue from four different gastroduodenal regions. The duodenum formed significantly greater amounts than the fundus, antrum, or corpus, which were similar. Intragastric HC1 produced a trend toward increased PGE 2 formation (pmol PGE 2/mg tissue) in the fundus, 143 ± 36 to 237 ± 57; corpus, 87 ± 13 to 200 ± 57; antrum, 157 ± 28 to 224 ± 65; and duodenum, 235 ± 56 to 338 ± 51. However, statistical significance was not reached. Intragastric HC1 combined with i.v. ASA reduced PGE 2 formation by tissue from all four regions below detectable levels. The data indicate that PGE 2α formation by rat gastroduodenal tissue differs regionally, and i.g. HCl perfusion did not significantly increase PGE 2 formation. However, when i.g. HCl perfusion combined with i.v. ASA, the PGE 2 formation was reduced below detectable levels.

Comparison of esophageal manometry, provocative testing, and ambulatory monitoring in patients with unexplained chest pain

Prolonged ambulatory esophageal pH and pressure monitors are being developed to evaluate noncardiac chest pain. This new technology needs comparison with conventional esophageal tests before determining which studies are most useful in diagnosing and treating esophageal chest pain. Therefore, we studied 45 patients with esophageal manometry, acid perfusion and edrophonium tests, and 24 hr pH and pressure monitoring. Manometry was abnormal in 20 patients (44%) with nutcracker esophagus, the most common motility disorder. Fifteen (33%) had positive acid perfusion test and 24 (55%) positive edrophonium test. During ambulatory monitoring, all patients experienced chest pain with a total of 202 individual events: 32 events (15%) secondary to acid reflux, 15 (7%) secondary to motility abnormalities, 7 (3%) to both pH and pressure changes, and 149 events (74%) occurred in the absence of any abnormal pH or motility changes. Patients with normal manometry were significantly (P less than 0.01) more likely to have acid reflux chest pain events than did nutcracker patients, who had an equal frequency of pH and motility events. A positive acid perfusion test was significantly associated with abnormal pressure events (P = 0.02; odds ratio 5.95), while a positive edrophonium test more likely predicted acid reflux chest pain during 24-hr monitoring (P = 0.007; odds ratio 7.25). Therefore, abnormal manometry and positive provocative tests point to the esophagus as the likely source of chest pain. However, ambulatory pH and pressure monitoring are required to accurately define the relationship between chest pain and acid reflux or motility disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipyridamole metabolic scintigraphy using i-123 phenylpentadecanoic acid vs dipyridamole thallium-201 perfusion imaging for the detection of coronary artery disease

Dipyridamole metabolic scintigraphy using i-123 phenylpentadecanoic acid vs dipyridamole thallium-201 perfusion imaging for the detection of coronary artery disease