Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

Objective: Barrett's esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barrett's esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barrett's patients than in patients with moderate or severe endoscopic esophagitis.
Methods: Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy ≤3 months before pH-metry. Included were 51 patients with Barrett's esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects.
Results: Patients with Barrett's esophagus had significantly increased acid reflux time (   p < 0.01  –0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (   p < 0.01  –0.05) reduced in patients with Barrett's esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis.
Conclusion: Although acid reflux is increased in patients with Barrett's esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barrett's esophagus.     

The Effect of Transcutaneous Nerve Stimulation on Sphincter of Oddi Pressure in Patients with Biliary Dyskinesia

Vasoactive intestinal polypeptide (VIP) has been postulated as a neuropeptide with inhibitory neurotransmitter activity in nonadrenergic noncholinergic pathways. Transcutaneous electric nerve stimulation (TENS) relaxes the lower esophageal sphincter in patients with achalasia. Such response is accompanied by a 30% increase in VIP concentrations in the systemic circulation. Since the sphincter of Oddi (SO) receives a very dense VIP nerve supply, we evaluate the effect of TENS on SO motor activity and on VIP plasma concentrations in patients with biliary dyskinesia and in healthy volunteers. TENS was performed with a pocket stimulator for 45 min. SO pressure and VIP levels were obtained before and after 45 min of TENS. In patients with SO dyskinesia, TENS produced a significant decrease in SO pressure from 80.1 +/- 11.9 mm Hg to 58.3 +/- 9.7 mm Hg p less than 0.01); this was accompanied by a significant increase in VIP plasma levels from 21.1 +/- 0.5 pg/ml to 32.6 +/- 1.5 pg/ml (p less than 0.01). In healthy volunteers, TENS did not produce significant changes in SO pressure. However, a significant increase in VIP plasma values was observed (p less than 0.01). No significant changes in amplitude, duration and frequency of SO phasic contractions were observed in either of the two groups evaluated. We conclude that, in patients with SO dyskinesia, TENS decreases SO basal pressure, possibly by a direct action of the released VIP in the systemic circulation. In healthy volunteers, TENS increases VIP plasma values without significant effect on SO basal pressure. These findings suggest that the response to TENS may be mediated by VIP. It is also possible that the alterations seen in patients with biliary dyskinesia may be due to impairment of the VIP nerve supply at the level of the SO.     

Barrett's esophagus. A prevalent, occult complication of gastroesophageal reflux disease

A prospective study of patients with symptoms of gastroesophageal reflux was undertaken to determine the prevalence of Barrett's esophagus and reevaluate the diagnostic approach necessary to detect this complication. Endoscopy with mucosal biopsy was performed in 97 subjects. Twelve (12.4%) were found to have Barrett's esophagus. The sensitivity and specificity of the endoscopic and radiologic examinations for Barrett's esophagus were prospectively evaluated. Endoscopy (92%) was significantly more sensitive than radiology (24%) in detecting Barrett's esophagus (p less than 0.001). The frequency and severity of reflux symptoms among patients determined to have Barrett's esophagus, reflux esophagitis, or normal esophageal biopsies were quantitatively similar in all three groups, except for significantly greater daytime heartburn in those with reflux esophagitis (p less than 0.01). These data indicate that Barrett's esophagus complicates gastroesophageal reflux more often than previously believed.     

Esophageal acid sensitivity in Barrett's esophagus

Esophageal acid sensitivity was evaluated in 15 patients with Barrett's esophagus and in 15 patients with reflux esophagitis uncomplicated by Barrett's. Patients with Barrett's esophagus had sensitivity to esophageal acid perfusion less frequently than those with uncomplicated reflux esophagitis (66 vs. 100%; p less than 0.05). Moreover, patients with Barrett's esophagus with acid sensitivity took longer to develop pain during acid perfusion (p less than 0.05), and overall, experienced less severe symptoms (p less than 0.01) than those with reflux esophagitis. Over a 2-week period, as judged by diary, the Barrett's group had less frequent (p less than 0.01) and less severe (p less than 0.01) heartburn symptoms than the other patients. These results indicate that patients with Barrett's esophagus have significantly reduced esophageal acid sensitivity and, as a consequence, have an impaired ability to recognize acid reflux.     

Familial clustering of reflux symptoms

OBJECTIVE: A number of case reports describe multiple family members with gastroesophageal reflux disease and Barrett' s esophagus. The wider importance of familial factors in gastroesophageal reflux disease has not been established. Therefore, we have studied the prevalence of reflux symptoms and medication use among relatives of patients with documented gastroesophageal reflux disease. METHODS: A postal questionnaire study of the first degree relatives of six groups of matched patients. The groups comprised patients with 1) no dyspeptic symptoms; 2) reflux symptoms and a normal pH study; 3) reflux symptoms, an abnormal pH study, and a lower esophageal sphincter (LOS) pressure more than 10 mm Hg; 4) reflux symptoms, an abnormal pH study, and a LOS pressure less than 10 mm Hg; 5) Barrett's esophagus; and 6) peptic stricture. RESULTS: Four hundred eighteen subjects replied (78% response). Infrequent reflux symptoms were equally common in all groups of relatives. Frequent reflux symptoms, however, were more common among relatives of patients with an abnormal pH study and normal (26%, p = 0.007) or low LOS pressure (27%, p = 0.01) or Barrett's esophagus (30%, p = 0.003), compared with relatives of nondyspeptic patients (9%). Frequent reflux symptoms were no more common among relatives of patients with a normal pH study (16%) or peptic stricture (18%). Reflux medication use showed a similar pattern. CONCLUSIONS: Familial clustering of reflux symptoms is seen in relatives of patients with reflux symptoms and increased esophageal acid exposure and in relatives of patients with Barrett's esophagus.     

Transcutaneous electrical nerve stimulation decreases lower esophageal sphincter pressure in patients with achalasia

Vasoactive intestinal peptide (VIP) is believed to be an inhibitory neurotransmitter responsible for lower esophageal sphincter (LES) relaxation. In patients with achalasia the concentration of VIP and the number of VIP-containing nerve fibers are reduced or absent. It has been suggested that the response to low-frequency transcutaneous electrical nerve stimulation (TENS) may be mediated by a nonadrenergic noncholinergic pathway in which the release of VIP is responsible for the smooth muscle relaxation. The present study was designed to evaluate the effect of TENS on LES pressure and on VIP plasma concentrations in six patients with achalasia (five female, one male). TENS was performed daily during one week for 45-min sessions with a pocket stimulator that delivered low-frequency pulses (6.5 Hz), at 10 pulses/sec of 0.1-msec duration at intensities of 10-20 mA until rhythmic flexion of the fingers was obtained without producing pain. LES pressure and VIP levels were obtained before TENS, after the first 45-min session, and after a week of daily stimulation. After 45-min, TENS produced a significant reduction (P less than 0.01) in LES resting pressure from the mean value 56 +/- 6.4 mm Hg to 42.3 +/- 6.4 mm Hg; with LES relaxation improvement from 50.6 +/- 3% to 63.1 +/- 3.2% (P less than 0.01). After one week of daily TENS, an additional reduction in LES resting pressure (40.3 +/- 4 mm Hg) was observed (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lower esophageal sphincter pressure in normal individuals and patients with gastroesophageal reflux. A comparison between end-hole and side-hole recording techniques

The advantage of a single-lumen end-hole catheter compared with the usual composite side-hole catheter for lower esophageal sphincter (LES) manometry has been studied in vitro and in vivo. In the present study LES pull-through manometry was performed with a special catheter, enabling simultaneous end-hole and side-hole recording of LES pressure. Eighteen normal individuals with normal 24-h pH-monitoring (control group) and 42 reflux patients with pathologic 24-h pH-monitoring (reflux group) were studied. End-hole recorded resting sphincter pressure (RSP) in the control group was 15.4 +/- 5.0 cm H2O and in the reflux group 6.4 +/- 6.4 (p less than 0.0005). Side-hole recorded RSP (mean S1-S3) was 20.8 +/- 11.6 and 11.9 +/- 6.8, respectively (p less than 0.005). End-hole recorded total sphincter length (SL) in the control group was 34 +/- 9 mm and in the reflux group 27 +/- 12 (p less than 0.025) and abdominal sphincter length (ASL) 23 +/- 7 and 16 +/- 9, respectively (p less than 0.005). Side-hole recorded SL was 30 +/- 7 and 30 +/- 12, respectively (NS) and ASL 22 +/- 6 and 18 +/- 9 respectively (NS). After intake of 500 ml of water both LES pressure and length decreased in both groups but the separation between the groups was neither improved nor impaired. The results support the view that LES insufficiency is an important cause of gastroesophageal reflux. That LES had a lower pressure and was shorter in patients with reflux was best demonstrated by end-hole recorded pressure.     

Barrett's esophagus, gastroesophageal acid reflux and duodenogastric reflux during the digestive and postprandial period]

Pathologic gastroesophageal acid reflux appears to be involved in the pathogenicity of Barrett's esophagus. The possible pathogenic role of duodenogastric reflux, however, has been suggested by several studies. The aim of this prospective study was to assess the prevalence of acid or duodenogastric reflux in patients with Barrett's esophagus. Nine patients with histologically proven Barrett's esophagus (mean length: 7.7cm; range: 2-13 cm) were studied by esophageal manometry and 24 hour pHmetry. Duodenogastric reflux was measured in the interdigestive period by aspiration and during the postprandial period using an isotopic method. The results of these different investigations were compared with healthy volunteers (n = 20 to 27). Three patients had complicated Barrett's esophagus (Barrett's ulcer: n = 2, high-grade dysplasia: n = 1). The results of the different investigations showed that a) all patients had abnormal acid exposure and an esophageal motor dysfunction (decrease in lower esophageal sphincter pressure, amplitude and duration of contractions and increase in percentage of peristaltic dysfunction); b) none of the patients had any pathologic duodenogastric reflux neither in the interdigestive nor in the postprandial period. These results a) confirm the high prevalence of acid reflux in patients with Barrett's esophagus, b) show that bile or pancreatic secretions are not involved in the pathogenicity of Barrett's esophagus.     

Comparison of Lower Esophageal Sphincter Manometrics and Gastroesophageal Reflux Measured by 24-Hour pH Recording

We compared lower esophageal sphincter (LES) pressures to parameters of acid reflux measured during 24-h pH monitoring in 81 patients being evaluated for possible reflux disease. Mid-respiratory LES pressures were significantly higher (p less than 0.05) in patients with normal amounts of reflux than in those with abnormal reflux. This difference did not occur with LES pressure measured by end-expiratory station pull-through (SPT) or rapid pull-through (RPT). There was no significant difference in total length or intra-abdominal portion of LES between the two groups. However, the product of LES pressure and total LES length was greater (p less than 0.05) for patients with normal reflux than for these with abnormal reflux. No difference was noted in the percentage of abnormal contractions in the distal esophagus between groups. These studies support the following conclusions: 1) LES pressure may be a more important protective mechanism against reflux than LES length. 2) Mid-respiratory SPT technique appears to identify the LES antireflux barrier better than either end-expiratory SPT or RPT techniques. 3) Acid exposure time seems to be a better measure of gastroesophageal reflux than the number of reflux episodes.     

CagA-positive strains of Helicobacter pylori may protect against Barrett's esophagus

OBJECTIVE: Helicobacter pylori (H. pylori) colonization is associated with chronic gastritis, peptic ulcer disease, and adenocarcinoma of the distal stomach. However, the role of H. pylori strain variation in complicated gastroesophageal reflux disease, especially Barrett's esophagus, is unknown. Therefore, the aim of this study was to evaluate the prevalence of colonization by cagA+ and cagA- H. pylori strains in the spectrum of gastroesophageal reflux disease, including Barrett's esophagus. METHODS: A total of 251 patients undergoing endoscopy were categorized into four groups: controls, patients with gastroesophageal reflux disease alone, and patients with short- and long-segment Barrett's esophagus. All patients underwent upper endoscopies with biopsies and serum collections. H. pylori and degree of mucosal inflammation in gastric biopsies were assessed and serological assessment made for H. pylori and cagA status. RESULTS: The overall prevalence of H. pylori colonization in the study population was 35% (95% confidence interval = 29.5-41.4%) which did not differ significantly among the groups. However, colonization by cagA+ H. pylori strains was significantly more prevalent among controls (11/25; 44%) and patients with gastroesophageal reflux disease (13/36; 36%) than in patients with short-segment (2/10; 20%) or long-segment Barrett's esophagus (0/18; 0%). Patients with Barrett's esophagus were less likely to be colonized by cagA+ H. pylori strains than reflux patients without Barrett's esophagus (odds ratio = 0.27, 95% confidence interval = 0.11-0.67, p = 0.004). CONCLUSIONS: Colonization by cagA+ H. pylori strains may be protective against the formation of short- and long-segment Barrett's esophagus and its malignant complications.     

Esophageal motor abnormalities in gastroesophageal reflux and the effects of fundoplication

Recordings of esophageal manometry obtained from 18 healthy control subjects and 32 patients with gastroesophageal reflux disease both before and after fundoplication were assessed. Preoperatively, the patients had a mean lower esophageal sphincter pressure at rest that was significantly lower (p less than 0.001) than that observed in the control group. The amplitude of peristaltic contractions, elicited by wet swallows, varied along the length of the esophagus. In patients with gastroesophageal reflux disease, the mean amplitudes recorded from the upper, middle, and lower esophagus were significantly lower (p less than 0.001) than those recorded from control subjects. No significant differences were observed between those patients with (53%) and without preoperative endoscopic evidence of esophagitis. After antireflux surgery (modified Nissen fundoplication), the mean amplitude of peristaltic contractions increased significantly (p less than 0.001) at all levels of the esophagus and were not significantly different from control values. This study describes motor abnormalities in the body of the esophagus associated with gastroesophageal reflux disease. These may arise secondary to gastroesophageal reflux inasmuch as they disappear after fundoplication.     

Quantification of Duodenogastric Reflux in Barrett's Esophagus

Objectives : Our objective was to assess the role of reflux of duodenal contents in the genesis of Barrett's esophagus. Therefore, we performed a study to quantify duodenogastric reflux, using ^99mTc-HIDA quantification in gastric juice after continuous intravenous infusion of the same. Methods : The study contained 20 patients with Barrett's esophagus (10 uncomplicated and 10 complicated by ulcers and/or stenosis), 10 patients with peptic esophagitis without Barrett's esophagus (two grade I, four grade II, and four grade III, according to Savary-Miller), and 10 healthy volunteers who made up the control group. Comparisons were made between the groups. Results : When we considered the groups overall, we observed that the 20 patients with Barrett's esophagus had higher reflux rates ( p < 0.01) than either the 10 patients with peptic esophagitis without Barrett's esophagus, or the 10 controls. Complicated Barrett's esophagus presented higher reflux rates than uncomplicated Barrett's esophagus, although the differences were not statistically significant. However, on analyzing the results after considering the groups case by case, we see that the mean reflux rate in the Barrett's esophagus groups is due to five patients presenting much higher rates than the rest. Conclusions : Our results suggest that duodenogastric reflux might be involved in the appearance of Barrett's esophagus and its related complications, although only in certain cases. The pathogenesis of Barrett's esophagus is probably multifactorial, and other factors must be involved.     

Gastroesophageal Reflux and Barrett''s Esophagus in Developmentally Disabled Patients

Twenty-seven patients from an institution for the developmentally disabled underwent endoscopy for evaluation of vomiting, regurgitation, rumination, or upper gastrointestinal bleeding. The presence of gastroesophageal reflux and Barrett's esophagus was determined retrospectively. Twenty-three patients had an IQ less than 20, 19 were nonambulatory, and 14 were taking at least one neuroleptic drug daily. Seven patients (26%) had histologically documented Barrett's esophagus of the specialized-columnar type. Two patients with Barrett's esophagus had benign esophageal strictures, but no cases of adenocarcinoma were found. There were no significant differences (p greater than 0.05) between patients with or without Barrett's esophagus in regard to symptoms, age, sex, IQ, medications, or ambulatory status. The present data suggest that Barrett's esophagus may frequently occur in developmentally disabled patients with symptoms and signs of gastroesophageal reflux.     

Gastroesophageal reflux and Barrett's esophagus in adults born with esophageal atresia

OBJECTIVE: Postoperative morbidity after correction of esophageal atresia is partly determined by gastroesophageal reflux disease, which has been proven to affect from one-half to two-thirds of patients during childhood. We conducted a follow-up study to test our hypothesis that, if former patients still show gastroesophageal reflux at adult age, they are at high risk for developing Barrett's esophagus, which is considered to be premalignant. METHODS: Of 69 patients born between 1971 and 1978, all having undergone a primary anastomosis, 24 had died, five of them because of aspiration. Of the 45 survivors, 39 could be traced; they all completed a questionnaire inquiring after symptoms related to the esophagus. Of these patients, 34 underwent an additional esophagogastrocopy. RESULTS: Only nine of the 39 patients had no symptoms at all; 30 had mild to severe dysphagia symptoms, and 13 had mild to severe reflux symptoms. Esophagogastrocopy in 34 patients revealed that the anastomosis was still recognizable in all cases, but stenoses were not found. Six patients showed a small hiatal hernia, and one a large one. The incidences of reflux symptoms (13/39, p < 0.01), reflux esophagitis (9/34, p < 0.01) and Barrett's esophagus (2/34, p < 0.001) were significantly higher than in the normal population. CONCLUSIONS: This group seems to be at risk for developing Barrett's esophagus. As this is the first follow-up study of a consecutive group of adult esophageal atresia patients, we think it is advisable to perform an esophagogastroscopy in all patients at adulthood until more long term follow-up data are available.     

Gastroesophageal Reflux Disease in the Elderly: More Severe Disease That Requires Aggressive Therapy

Objective: To evaluate gastroesophageal reflux disease in the elderly (people ≥ 60 yr). Methods: Basal gastric-acid secretion was prospectively determined in 228 consecutive patients with symptomatic gastroesophageal reflux disease who had upper gastrointestinal endoscopy and were diagnosed with either pyrosis alone (n = 98), erosive esophagitis (n = 87), or Barrett's esophagus (n = 43). Results: Patients ≥ 60 yr (n = 66) had significantly more esophageal mucosal disease (erosive esophagitis, Barrett's esophagus) than patients < 60 yr (n = 162)- 81% versus 47% ( p = 0.000002, Fisher's exact test). Furthermore, 87% of patients ≥ 70 yr had esophageal mucosal disease. For each decade from < 30 yr to ≥ 70 yr, there was a significant increase in esophageal mucosal disease ( p = 0.002; X ² test, 23.96); however, there were no significant differences in severity of pyrosis symptoms or in mean basal acid output for each decade. When 146 of the 228 patients with gastroesophageal reflux disease were given enough ranitidine (mean, 630 mg/d; range, 300–3000 mg/d) for the relief of all pyrosis symptoms and healing of all esophageal mucosal disease, there were no significant differences in ranitidine therapy between each decade. Conclusions: Elderly patients with pyrosis symptoms severe enough to require upper gastrointestinal endoscopy have gastroesophageal reflux disease with more esophageal mucosal disease (erosive esophagitis, Barrett's esophagus) than patients < 60 yr, and like younger patients, may require markedly increased doses of ranitidine as large as 2400 mg/d for effective therapy.     

Acute hemodynamic effects of alpha human atrial natriuretic polypeptide in patients with congestive heart failure

Acute hemodynamic and humoral effects of synthesized alpha human atrial natriuretic polypeptide (alpha-hANP, 0.025 microgram/kg/min for 40 min) on 6 patients with severe congestive heart failure were assessed. Plasma alpha-hANP concentration was high in patients and increased further (from 463 +/- 360 to 1,282 +/- 670 pg/ml, mean +/- SD, p less than 0.01) following alpha-hANP infusion, but plasma norepinephrine (1,030 +/- 865 to 971 +/- 785 pg/ml) was not changed. Increases in urine output (1.0 +/- 0.8 to 2.6 +/- 2.3 ml/min) and Na+ excretion rate (87 +/- 89 to 257 +/- 211 mEq/min/m2) were statistically insignificant. A significant reduction was induced in mean aortic pressure (99 +/- 25 to 96 +/- 26 mmHg, p less than 0.05), mean right atrial pressure (11 +/- 9 to 7 +/- 8 mmHg, p less than 0.01), mean pulmonary arterial pressure (39 +/- 13 to 33 +/- 12 mmHg, p less than 0.05) and mean pulmonary capillary wedge pressure (27 +/- 8 to 20 +/- 7 mmHg, p less than 0.01). Heart rate, cardiac index, systemic vascular resistance and pulmonary vascular resistance were not altered. In conclusion, alpha-hANP induced decreases in left ventricular filling pressure and rightside heart pressure which were attributed to venodilatation rather than natriuresis in patients with congestive heart failure. Preserved cardiac output with decreased preload suggested that alpha-hANP improved cardiac function.     

Time pattern of gastric acidity in Barrett's esophagus

Increased gastroesophageal acid reflux is frequently found in patients with Barrett's esophagus, and it has been hypothesized that gastric acid hypersecretion could be an important factor aggravating the exposure of esophageal mucosa to acid and then contributing to the development of this disorder. The aim of the present study was to assess whether the circadian pattern of gastric acidity differs between refluxer patients with and without Barrett's esophagus and normal subjects. Continuous 24-hr gastric pH monitoring was performed in 119 healthy volunteers, 20 patients with Barrett's esophagus, 37 patients with moderate and 10 patients with severe reflux esophagitis without Barrett's esophagus. In all these diseases the final diagnosis was ascertained by means of endoscopy plus biopsy. There was no difference in the 24-hr and daytime patterns of gastric pH between healthy subjects and patients with Barrett's esophagus, while nocturnal acidity was significantly lower (P<0.05) in the latter population. Gastric acidity, in contrast, was higher (P<0.05) in controls than in patients with both moderate and severe reflux esophagitis without Barrett's esophagus during the whole 24-hr period. There was no difference between refluxer patients with and without Barrett's esophagus in any of the three time intervals we analyzed. Because normal subjects had lower gastric pH than patients with Barrett's esophagus during the night and than patients with reflux esophagitis during the whole 24-hr period, gastric hyperacidity is not a relevant factor in the development of both metaplastic columnar epithelium and inflammatory changes in the distal esophagus, and other pathophysiological mechanisms are involved in these histological alterations.     

Correlation of gastroesophageal reflux disease symptoms characteristics with long-segment Barrett''s esophagus

Thus far, there has been a paucity of studies that have assessed the value of the different gastroesophageal reflux disease (GERD) symptom characteristics in identifying patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus. To determine if any of the symptom characteristics of GERD correlates with long-segment Barrett's esophagus versus short-segment Barrett's esophagus. Patients seen in our Barrett's clinic were prospectively approached and recruited into the study. All patients underwent an endoscopy, validated GERD symptoms questionnaire and a personal interview. Of the 88 Barrett's esophagus patients enrolled into the study, 47 had short-segment Barrett's esophagus and 41 long-segment Barrett's esophagus. Patients with short-segment Barrett's esophagus reported significantly more daily heartburn symptoms (84.1%) than patients with long-segment Barrett's esophagus (63.2%, P = 0.02). There was a significant difference in reports of severe to very severe dysphagia in patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus (76.9%vs. 38.1%, P = 0.02). Longer duration in years of chest pain was the only symptom characteristic of gastroesophageal reflux disease associated with longer lengths of Barrett's mucosa. Reports of severe or very severe dysphagia were more common in long-segment Barrett's esophagus patients. Only longer duration of chest pain was correlated with longer lengths of Barrett's esophagus.     

Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis

Hemodynamic and neurohumoral responses to acute diuretic therapy were measured in 15 patients with severe chronic heart failure given intravenous furosemide, 1.3 +/- 0.6 (SD) mg/kg body weight. Left ventricular pump function deteriorated by 20 minutes, as indicated by a fall in stroke volume index (27 +/- 8 to 24 +/- 7 mL/min X m2 body surface area, p less than 0.01) and an increase in left ventricular filling pressure (28 +/- 7 to 33 +/- 9 mm Hg, p less than 0.01). Increases occurred in heart rate (87 +/- 13 to 91 +/- 16 beats/min, p less than 0.01), mean arterial pressure (90 +/- 15 to 96 +/- 15 mm Hg, p less than 0.01), systemic vascular resistance (1454 +/- 394 to 1676 +/- 415 dynes X s X cm-5, p less than 0.01), plasma renin activity (9.9 +/- 8.5 to 17.8 +/- 16 ng/mL X h, p less than 0.05), plasma norepinephrine level (667 +/- 390 to 839 +/- 368 pg/mL, p less than 0.01), and plasma arginine vasopressin level (6.2 +/- 1.3 to 8.3 +/- 2.0 pg/mL, p less than 0.01). During the next 3.5 hours the patients had diuresis (2085 +/- 1035 mL) and the expected fall in filling pressure (28 +/- 7 to 22 +/- 10 mm Hg, p less than 0.01). Neurohumoral indicators also returned toward the control levels. Intravenous furosemide, in patients with severe chronic heart failure, is associated with acute pump dysfunction temporally related to activation of the neurohumoral axis.