Reproducible demonstration of blood flow at duodenal ulcer margins by endoscopic reflectance spectrophotometry

Changes in gastrointestinal mucosal blood flow were evaluated by index of oxygen saturation (ISO2) and index of hemoglobin concentration (IHB) measured with a reflectance spectrophotometer. This report examined the reproducibility of endoscopic measurements of ISO2 and IHB. Study 1: The everted stomachs of three anesthetized rats provided hands-on instruction (one teacher and three learners). Six sets of readings were obtained endoscopically (the mean calculated to give the measurement) at each level of gastric mucosal perfusion when gastric blood flow was varied by withdrawing blood from the carotid artery. Study 2: Fourteen duodenal ulcer patients with ulcer bleeding were transfused and stabilized. Two endoscopists (one teacher and one learner) took turns to obtain endoscopic ISO2 and IHB measurements at the margin of the ulcer and at the adjacent normal appearing mucosa. delta ISO2 was calculated as the ulcer margin value minus adjacent mucosa value. In study 1, the correlation coefficients between the ISO2 measurements of the experienced and those of the other three observers were 0.99, 0.97, and 0.97, respectively. In study 2, the correlation coefficients between the ISO2 measurements obtained at the ulcer margin and at the adjacent normal mucosa, and delta ISO2 obtained by the experienced observer and one of the three learners were 0.94, 0.97, and 0.94, respectively. Relative to the adjacent area, 79% of the duodenal ulcers studied had increased (+delta ISO2), and 21% had decreased blood flow (-delta ISO2) at the ulcer margins. IHB measurements were less reproducible, particularly at the ulcer margin. The measurements of ISO2 and delta ISO2 were reproducible in the everted rat stomach and in duodenal ulcer patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic hemodynamics in patients with chronic hepatitis or cirrhosis as assessed by organ-reflectance spectrophotometry

Hepatic hemodynamics in patients with chronic liver disease has been studied by reflectance spectrophotometry of the liver in situ during peritoneoscopy. An organ-reflectance spectrophotometer used in this study was equipped with a branched optic fiber bundle, which coupled the liver surface with the spectrophotometer. The spectrophotometry could measure qualitatively and quantitatively the absorption of hemoglobin in the liver in situ, thus estimating the regional hepatic tissue blood hemoglobin concentration and the saturation level of hemoglobin in the regional tissue blood. The analysis of 42 cases has shown that the estimated regional hepatic tissue blood hemoglobin concentration and saturation level of hemoglobin decreased in most cirrhotic livers, suggesting that even in cirrhotic livers the hepatic oxygen extraction increased, concomitant with a decrease in the regional hepatic tissue blood hemoglobin concentration. The hepatic blood hemoglobin concentration estimated on the surface layer of the liver was positively correlated with the regional hepatic blood flow measured by radioisotope clearance technique. The estimated hepatic blood hemoglobin concentration was also correlated positively with serum albumin level and prothrombin time, and negatively correlated with plasma retention of indocyanine green at 15 min. It is concluded that the hepatic tissue blood hemoglobin concentration decreases significantly with progress of chronic hepatitis to cirrhosis. This decrease in hepatic blood hemoglobin concentration and flow is concomitant with a decrease in metabolic functions, which is not compensated by an increased hepatic oxygen extraction.     

Endoscopic Reflectance Spectrophotometry and Visible Light Spectroscopy in Clinical Gastrointestinal Studies

The use of reflectance spectrophotometry (RS) for mucosal hemodynamic measurement relies on the recognition of changes in indexes of mucosal hemoglobin concentration and oxygen saturation. Endoscopic application in clinical studies has confirmed important observations demonstrated in animal experiments. The vasoconstriction induced by propranolol, vasopressin, glypressin, or somatostatin in the portal hypertensive gastric mucosa and the reduction of gastroduodenal mucosal perfusion by nonsteroidal anti-inflammatory drugs (NSAIDs) or smoking, mesenteric venoconstriction associated with systemic hypoxia, and acid-induced duodenal hyperemia are important examples. Prognostic predictions include the development of stress-induced gastric ulcerations in patients with significant reductions in gastric perfusion after thermal or head injury, or the demonstration of delayed gastric or duodenal ulcer healing when the hyperemia at the ulcer margin fails to materialize. In mechanical-ventilator-dependent patients with sepsis, a significantly reduced gastric mucosal RS measurement portends a grave prognosis (mortality >80%). Recent advances in technology resulted in the construction and validation of instruments for visible light spectroscopy. Measurements focused on tissue oxygen saturation demonstrated epinephrine and vessel-ligation-induced vasoconstriction, the absence of ischemia in radiation-induced rectal telangiectasias, and gut ischemia responsive to revascularization treatment. Endoscopic RS and visible light spectroscopy are suitable for assessing the role of blood flow in conditions with a lesser degree of ischemia and for testing the hypothesis that functional dyspepsia and dysmotility syndromes may be due to gut ischemia.     

Relationship between gastric mucosal hemodynamics and gastric motility

Continuous measurement of gastric mucosal hemodynamics (the index of mucosal hemoglobin concentration, the index of oxygen saturation and blood flow) in rats showed oscillatory changes. The mechanism of the oscillations was investigated using a probe specially designed for simultaneous measurement of hemodynamics and intragastric pressure. A hemodynamics-measuring probe for either reflectance spectrophotometry or laser-Doppler flowmetry was tied to a pressure microtransducer, inserted through an incision in the forestomach, and brought into gentle contact with the corpus mucosa. Synchronous oscillatory changes (4-6 cycles/min) in hemodynamics and motility were observed in the resting state (mean blood pressure: 120 mmHg). During moderate hemorrhagic hypotension (mean: 81 mmHg), oscillations in the hemodynamics increased in both amplitude and frequency, while motility remained constant. Oscillations in the hemodynamics were also affected by fluctuations in blood pressure and by topical application of norepinephrine to the corpus serosa. In water-immersion restraint rats, changes in the oscillations in the hemodynamics and motility were virtually synchronous; frequency decreased and amplitude increased. These findings suggest that oscillatory changes in gastric mucosal hemodynamics are regulated not only by gastric motility but also by arteriolar vasomotion of the gastric wall.     

Relationship between gastric mucosal hemodynamics and gastric motility

Continuous measurement of gastric mucosal hemodynamics (the index of mucosal hemoglobin concentration, the index of oxygen saturation and blood flow) in rats showed oscillatory changes. The mechanism of the oscillations was investigated using a probe specially designed for simultaneous measurement of hemodynamics and intragastric pressure. A hemodynamics-measuring probe for either reflectance spectrophotometry or laser-Doppler flowmetry was tied to a pressure microtransducer, inserted through an incision in the forestomach, and brought into gentle contact with the corpus mucosa. Synchronous oscillatory changes (4-6 cycles/min) in hemodynamics and motility were observed in the resting state (mean blood pressure: 120 mmHg). During moderate hemorrhagic hypotension (mean: 81 mmHg), oscillations in the hemodynamics increased in both amplitude and frequency, while motility remained constant. Oscillations in the hemodynamics were also affected by fluctuations in blood pressure and by topical application of norepinephrine to the corpus serosa. In water-immersion restraint rats, changes in the oscillations in the hemodynamics and motility were virtually synchronous; frequency decreased and amplitude increased. These findings suggest that oscillatory changes in gastric mucosal hemodynamics are regulated not only by gastric motility but also by arteriolar vasomotion of the gastric wall.     

Colonic mucosal hemodynamics and tissue oxygenation in patients with ulcerative colitis: Investigation by organ reflectance spectrophotometry

Colonic mucosal hemodynamics were investigated at the rectosigmoidal region of the colon in 46 patients with ulcerative colitis and in 18 normal subjects by organ reflectance spectrophotometry under colonoscopy. The value for the index of mucosal hemoglobin concentration (IHb) was significantly higher, and value for the index of mucosal hemoglobin oxygen saturation (ISO₂) was significantly lower in patients with active ulcerative colitis than values in the normal controls or in patients with inactive ulcerative colitis. The results indicate mucosal congestion and hypoxemia in patients with active ulcerative colitis. The changes in IHb and ISO₂ correlated well with the severity of ulcerative colitis scored by endoscopic findings and with the number of infiltrating inflammatory cells in the mucosa analyzed histologically in biopsy samples. In conclusion, the colonic mucosal microcirculation in patients with active ulcerative colitis was disturbed and showed congestion and hypoxemia. The analysis of hemodynamic changes may be helpful for assessing the activity of ulcerative colitis.     

Assessment of mucosal hemodynamics in normal human colon and patients with inflammatory bowel disease

Reflectance spectrophotometry measures indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2). In the rat colon, characteristic patterns of IHB and ISO2 are associated with ischemia with congestion (increased IHB and decreased ISO2) and ischemia without congestion (decreased IHB and decreased ISO2). Endoscopic measurements with acceptable interobserver variability was demonstrated in the canine stomach. In eight healthy subjects, endoscopic measurement in different areas of the colon and rectum revealed significantly lower IHB values in the splenic flexure. These observations are compatible with reduced flow and increased susceptibility to ischemic damage in this watershed area. The endoscopic measurements in 13 patients with active inflammatory bowel disease revealed an increase in IHB and ISO2 values in the involved areas, indicating an increase in mucosal blood flow. In six patients restudied when the disease remitted, these values returned to normal.     

Measurement of mucosal capillary hemoglobin oxygen saturation in the colon by reflectance spectrophotometry

BACKGROUND: Advances in optical and computer technology have enabled the development of a device that uses white-light reflectance spectrophotometry to measure capillary hemoglobin saturation in intestinal mucosa during colonoscopy. METHODS: Studies were performed with the colon oximeter in anesthetized animals and patients undergoing colonoscopy. RESULTS: Mean (SD) mucosal hemoglobin saturation in the normal colon was 72% (3.5%). In an animal model, ischemia induced by arterial ligation and hypoxemia via hypoxic ventilation each resulted in a decrease of over 40% in the mucosal saturation. In patients with colon polyps, ischemia induced by epinephrine injection, stalk ligation with a loop, or clipping of the polyp stalk each resulted in a decrease of over 40% in the mucosal saturation (p < 0.02). In contrast, saline solution injection did not decrease the mucosal saturation. CONCLUSIONS: A novel device for measuring capillary hemoglobin saturation in intestinal mucosa during colonoscopy is capable of providing reproducible measurements in normal patients and clearly detects dramatic decreases in saturation with ischemic and hypoxic insults.     

Hepatic Circulation and Hepatic Oxygen Consumption in Alcoholic and Nonalcoholic Fatty Liver

The purpose of this study was to determine the differences in hepatic circulation and oxygen consumption in two groups: those with nonalcoholic obesity-related fatty live and those with alcoholic fatty liver. Although the histological degree of fatty infiltration was equal in the two groups, the delta Er569-650, as an index of the regional liver blood flow estimated by spectrophotometric method, was significantly lower in alcoholic fatty liver than in nonalcoholic fatty liver, and the in vivo hepatic oxygen consumption (VO2), also determined by hepatic reflectance spectrophotometry during peritoneoscopy, tended to be lower in alcoholic fatty liver than in nonalcoholic fatty liver. The oxygen saturation of hemoglobin in local liver blood (SO2) was, however, significantly higher in alcoholic fatty liver than in nonalcoholic fatty liver. These results suggest that an increase in oxygen extraction to maintain oxygen consumption, which was indicated by the lowering of the SO2, was not found in alcoholic fatty liver, in spite of a reduction of oxygen supply to the liver. It is concluded that the impairment of hepatic circulation and hepatic oxygen consumption was more serious in alcoholic fatty liver than in nonalcoholic fatty liver, possibly contributing to a different prognosis for the two forms of fatty liver.     

Reflectance spectrophotometry in the gastrointestinal tract: limitations and new applications

OBJECTIVES: Reflectance spectrophotometry (RS) assesses blood flow changes by measuring an index of Hb concentration (IHB) and index of Hb oxygen saturation (ISO2). We tested the following hypotheses: 1) endoscopic RS measurements obtained by two observers and with the aid of fiber optic and video endoscopes are similar, and 2) the method is suitable for documenting mesenteric venoconstriction associated with systemic hypoxia and blood flow autoregulation associated with hemorrhagic hypotension. METHODS: Study 1: two investigators obtained baseline gastric mucosal RS measurements in anesthetized rats (n = 3) before and after stepwise reduction of blood pressure induced by arterial hemorrhage. Study 2: subjects were examined by both fiber optic and video endoscopes. Endoscopic RS measurements were obtained at 20 cm from the anal verge. Study 3: video endoscope was used to obtain RS measurements in oxygen-dependent patients on and off oxygen treatment. Study 4: the procedures in study 1 were repeated in five additional rats by one of the investigators. RESULTS: Study 1: there was good agreement between the measurements of IHB and ISO2 between the two investigators. Study 2: video endoscope-assisted measurements were consistently lower. Study 3: cessation of oxygen treatment produced a significant drop in oxygen saturation (pulse oximetry), decline in ISO2, and rise in IHB. Study 4: when blood pressure varied between 90% and 40% of baseline, gastric mucosal blood flow (IHB) was maintained at approximately 70% of baseline level. CONCLUSIONS: We confirmed that reproducible measurement can be obtained by different investigators using standardized techniques. Standardization of endoscopic equipment is also necessary to overcome the significant limitation of endoscopic equipment on RS measurements. RS measurements can document mesenteric venoconstriction associated with systemic hypoxia and blood flow autoregulation associated with hemorrhagic hypotension.     

Effect of submucosal epinephrine injection on local gastric blood flow

Clinical studies have demonstrated the efficacy of submucosal epinephrine injection in the control of bleeding ulcers. Since endoscopic techniques for assessing gastroduodenal blood flow are limited, we employed an animal model to study the mechanism of control of bleeding. The effect of submucosal epinephrine injection on local gastric blood flow was studied in the rat using laser Doppler flowmetry and reflectance spectrophotometry. Submucosal injection of 0.1 ml of 1/10,000 epinephrine caused a significantly greater drop in local gastric blood flow (laser Doppler flowmetry) compared with vehicle (10% sodium metabisulfite) injection. The reduction persisted for up to 120 min. This vasoconstrictive effect of epinephrine was confirmed by observations with reflectance spectrophotometry, which documented a pattern of ischemia without congestion (lower index of hemoglobin concentration, lower index of oxygen saturation). The autoregulatory escape from adrenergic vasoconstriction was not evident in either instance. We conclude that, after submucosal injection of epinephrine, the absence of autoregulatory escape from adrenergic vasoconstriction and the marked and prolonged decrease in local gastric blood flow enhance the homeostatic mechanisms (eg, platelets and other coagulative factors) to effect hemostasis in bleeding ulcers.     

Influence of ranitidine on hepatic blood flow assessed by organ-reflectance spectrophotometer and pulse-doppler ultrasonic flowmeter

The influence of the intravenous injection of ranitidine (50 mg) on hepatic hemodynamics was investigated in normal subjects and patients with chronic liver disease. Using the organ-reflectance spectrophotometer, the regional hepatic blood hemoglobin concentration (delta Er569-650), an indicator of the regional hepatic blood flow, and the oxygen saturation of hemoglobin in the regional hepatic tissue (So2) were measured in patients with chronic liver disease after ranitidine injection under peritoneoscopy. With the pulse-Doppler ultrasonic flowmeter, the portal blood flow was measured in patients with chronic liver disease and normal subjects. There were no significant changes in the regional hepatic blood flow, the oxygen saturation of hemoglobin, and the portal blood flow after the intravenous injection of ranitidine. Thus, it is concluded that usual dose of ranitidine has no significant influence on the hepatic blood flow and that it can be prescribed without reducing the hepatic blood flow.     

Gastroduodenal Perfusion and Mortality in Mechanical Ventilation-Dependent Patients with Systemic Inflammatory Response Syndrome

The role of gastrointestinal blood flow determination in predicting mortality is not known. We tested the hypothesis that when mechanical ventilation-dependent (MVD) patients with systemic inflammatory response syndrome (SIRS) develop a significant reduction in gastroduodenal blood flow, high mortality will ensue. The design was a prospective, observational study at the intensive care unit (study patients) and outpatient endoscopy suite (controls) of a tertiary care Veterans Affairs Hospital. There were 6 study patients and 10 control subjects. Interventions were endoscopic reflectance spectrophotometry recorded indexes of gastroduodenal mucosal oxygen saturation (ISO2) and hemoglobin concentration (IHB). Data for Acute Physiologic and Chronic Health Evaluation (APACHE) II scores were gathered. All study patients had septic SIRS at enrollment. Gastroduodenal blood flow measurements ranged from 32 to 55% (ISO2) and from 42 to 51% (IHB) of those in control subjects. The significant hypoperfusion upgraded diagnosis to severe sepsis. The APACHE II score of 16.8 +/- 2.8 (mean +/- SE) predicted approximately 25% mortality. Observed in-hospital mortality was 83%. Our study confirmed that MVD patients with severe sepsis have a significant impairment of gastroduodenal blood flow. Such a dramatic reduction is associated with a grave prognosis. The impact of these measurements on physicians' predictions of the likelihood of survival in patients receiving intensive care deserves to be assessed.     

Factors influencing systemic arterial oxygen saturation in complete transposition of the great arteries

Hemodynamic data from 100 patients with complete transposition of the great arteries, all 1 year old or older, were reviewed. Only 2 patients, at rest and breathing room air, had a systemic arterial oxygen saturation level as high as 85 percent. In any patient with dextrotransposition of the great arteries and a systemic arterial saturation of 85 percent or greater, there is a strong likelihood of a single ventricle.

At a given level of oxygen consumption, 3 potential variables influence systemic arterial oxygen saturation in transposition: (1) magnitude of the intercirculatory mixing, (2) hemoglobin concentration and (3) magnitude of the recirculated systemic mixed venous flow. The first 2 factors are directly related to systemic saturation, and the third is inversely related.

Decreasing total pulmonary blood flow, secondary to increasing pulmonary vascular disease or pulmonary stenosis, results in decreased intercirculatory mixing and a decrease in systemic arterial oxygen saturation. This decrease in saturation is partially compensated for by an increase in hemoglobin concentration. An index calculated from the level of systemic arterial oxygen saturation divided by the value for hemoglobin concentration is useful in follow-up studies to determine the presence of pulmonary vascular disease or pulmonary stenosis. This index will often eliminate the need for repeated cardiac catheterizations before definitive corrective surgery is carried out.     

Characterization of hepatic hemodynamics in cirrhotics and non-cirrhotics. Effect of glucagon infusion

The effect of glucagon on hepatic regional hemodynamics was investigated in patients with chronic liver disease during peritoneoscopy with reflectance spectrophotometry. When glucagon was infused intravenously in patients with a non-cirrhotic liver, the regional hepatic tissue oxygen consumption, as estimated spectrophotometrically, increased significantly, whereas the index of hepatic tissue blood volume did not change appreciably, and consequently, the oxygen saturation of hemoglobin in the hepatic tissue blood decreased. In contrast, the administration of glucagon in patients with liver cirrhosis resulted in a significant increase in the index of hepatic tissue blood volume and produced a minor increase in hepatic tissue oxygen consumption. The oxygen saturation of hepatic blood hemoglobin tended to increase in the cirrhotics. The result suggests the presence of functional vasoconstriction at the presinusoidal and/or sinusoidal vessels in the cirrhotic liver, possibly due to a decreased vasomotor activity and/or an abnormal regulatory function of vasoactive substances, which are released by glucagon.     

Blood oxygen measurements in the assessment of intracardiac left to right shunts: A critical appraisal of methodology

The proper use of sequential diagnostic blood oxygen determinations for assessing left to right shunts requires a thorough understanding of the normal variability of blood oxygen measurements among the various right heart chambers and the influence of alterations in circulating hemoglobin levels and systemic blood flow. Oximetric measurements were obtained in 23 patients without a left to right shunt and compared with measurements obtained in 42 patients with a proved left to right shunt to examine the normal range of oxygen variability in blood samples from right heart chambers. The effect of fluctuations in hemoglobin levels was evaluated by comparing increases in percent oxygen saturation and oxygen content. Differences in percent saturation were found to be more useful than differences in oxygen content for detection of cardiac shunts. A mean difference of at least 7 percent oxygen saturation was found to be required for a firm diagnosis of a shunt at the atrial level, and 5 percent oxygen saturation for a shunt at the ventricular or great vessel level.The curvilinear relation between systemic blood flow and oxygen step-up in determining the pulmonary to systemic flow ($\text{Q}{}_{\mathrm{P}}\text{Q}{}_{\mathrm{S}}$) ratio was expressed in a series of equations and depicted by a three dimensional surface. Interventions such as exercise augment both systemic blood flow and oxygen step-up, resulting in a shift to a more steeply rising portion of the surface and a dramatic increase in shunt flow. The minimal left to right shunt detectable with oxlmetry is largely dependent on the level of systemic blood flow.     

Reduction in index of oxygen saturation at margin of active duodenal ulcers may lead to slow healing

This study tested the hypothesis that reduced perfusion of a duodenal ulcer margin (ie, the mucosa 1–2 mm from the edge of the ulcer base) is associated with slow healing. Reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and mucosal hemoglobin oxygen saturation (ISO₂) were obtained endoscopically in 21 patients at the ulcer margin and the adjacent mucosa (ie, the mucosa 1–2 cm from the edge of the ulcer base). In 17 patients with adequate follow-up, stepwise multilinear regression analysis revealed a significantly negative correlation (r=s-0.69, P < 0.05) between ISO₂ at the ulcer margin minus ISO₂ at the adjacent mucosa (ISO)₂ and ulcer healing time. In addition, smoking, being black, and early relapse since the last ulcer attack were found to be associated with increased duration required for healing. The results of this pilot study suggest factors, in addition to smoking, that may have to be considered in future studies concerned with duodenal ulcer healing.This work was supported by the National Institute of Arthritis and Metabolism and Digestive Diseases Grant AM34840, American Society for Gastrointestinal Endoscopy Career Development Award H850208, Veterans Administration Medical Research Funds, and UCLA Academic Senate Grant 4063.     

Increased gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy.

To characterize gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy, 34 cirrhotics with this lesion and 24 noncirrhotics were studied by reflectance spectrophotometry and laser-Doppler flowmetry during endoscopy. A significant correlation was observed between the hemoglobin content of the gastric mucosa, measured by reflectance spectrophotometry, and the serum hemoglobin concentration both in cirrhotics (r = 0.72) and in noncirrhotics (r = 0.87). IHb ratio (hemoglobin content of gastric mucosa divided by blood hemoglobin concentration) was higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001), whereas the oxygen content of the gastric mucosa was similar in both groups. This pattern indicates that cirrhotics with portal hypertensive gastropathy have increased gastric perfusion without congestion. Gastric blood flow estimated by laser-Doppler was significantly higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001). In cirrhotic patients, gastric areas with cherry red spots showed a significantly higher IHb ratio than areas with a mosaic or scarlatina pattern (P < 0.05). The magnitude of changes in gastric perfusion and the endoscopic severity of portal hypertensive gastropathy had no relationship with the degree of portal hypertension or the azygos blood flow.     

Effect of cigarette smoking on the gastric mucosal blood volume index and hemoglobin oxygenation in man

The acute effect of cigarette smoking on the gastric mucosal blood volume index and the oxygen saturation of hemoglobin (SO2) in the gastric mucosa was investigated in 12 young male volunteers using reflectance spectrophotometry during endoscopy. Six of these volunteers were habitual smokers who had smoked more than 20 cigarettes a day for more than five years. The others were non-habitual smokers who smoked less than 20 cigarettes a year. The indices of mucosal blood volume and the mucosal blood SO2 level were calculated from the spectra obtained at the lesser curvature of the lower corpus of the stomach before and after cigarette smoking. The indices of mucosal blood volume and mucosal blood SO2 decreased significantly after one to three puffs of cigarette smoking in all subjects as compared to the value before smoking, and the degree of decrease in these parameters was significantly greater in the non-habitual smokers than in the habitual smokers. These results suggest that only one to three puffs of cigarette smoking causes a decrease in the mucosal blood volume and the mucosal blood SO2 which might be related to weakening of mucosal defensive factors.     

Effects of chronic normovolemic anemia on gastric microcirculation and ethanol-induced gastric damage in rats

The effects of chronic normovolemic anemia on gastric microcirculation and gastric mucosal susceptibility to ethanol-induced gastric damage were investigated in anesthetized rats. Blood exchange by a plasma expander during four consecutive days rendered the animals anemic with a 34% decrease in the baseline hematocrit but without affecting blood volume. Chronic anemia induced a decrease in whole blood viscosity, an increase in gastric mucosal blood flow measured by hydrogen gas clearance, a decrease in gastric vascular resistance, and a decrease in gastric hemoglobin content without changes in the gastric oxygen content, the latter two parameters being measured by reflectance spectrophotometry. Gastric mucosal blood flow was lowered by intragastric administration of 100% ethanol in both anemic and control rats, but the final blood flow was significantly higher in anemic than in control animals. Macroscopic gastric damage induced by ethanol administration was significantly lower in anemic than in control rats. We conclude that chronic normovolemic anemia increases gastric mucosal blood flow and leads a protecting mechanism against gastric mucosal damage induced by absolute ethanol.