Spider Angiomas in Patients with Liver Cirrhosis: Role of Alcoholism and Impaired Liver Function

A study was undertaken to compare two new methods of capillary blood flow measurement, namely fluorescein flowmetry (FF) and laser Doppler flowmetry (LDF). The blood flow was measured in a pelvic pouch during its construction and in the completed ileoanal anastomosis in 12 patients. There was a high correlation between the two methods (correlation coefficient, 0.78) (p <0.01) when the blood flow was measured in the pelvic pouch. The correlation coefficient between the two methods for the difference between the blood flow in the pelvic pouch at the site of the planned anastomosis when the pouch resided in the abdomen and that in the completed ileoanal anastomosis was r = 0.99 (n = 12, p< 0.001); the reduction amounted to 25% as measured by FF and 27% as measured by LDF (n = 12, p < 0.01). All ileoanal anastomoses healed perfectly, the lowest FF and LDF values being 0.004 density units/sec and 0.3 V, respectively. The results indicate that either method can be considered for measuring capillary blood flow.     

Acute effects of Helicobacter pylori extracts on gastric mucosal blood flow in the mouse

AIM： To investigate the mechanisms underlying the reduction in gastric blood flow induced by a luminal water extract of Hellcobacter pylori （HPE）. METHODS： The stomachs of isoflurane-anesthetized mice were exteriorized, and the mucosal surface exposed. Blood flow was measured with the laserDoppler technique, and systemic arterial blood pressure monitored. C57BL/6 mice were exposed to water extract produced from Hpylori strain 88-23. To investigate the role of a nerveor iNOS-mediated pathway, we used intraluminal lidocaine and iNOS-/- mice. Blood flow response to the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine （ADMA） was also assessed. RESULTS： In wild-type mice, HPE decreased mucosal blood flow by approximately 30%. This reduction was abolished in iNOS-deficient mice, and by pre-treatment with lidocaine. Luminally applied ADMA resulted in reduction in blood flow similar to that observed in wildtype mice exposed to HPE. CONCLUSION： A H py/ori water extract reduces gastric mucosal blood flow acutely through iNOS- and nerve-mediated pathways.     

Dopaminergic control of gastric mucosal blood flow in humans

We studied the dopaminergic regulation of the gastric mucosal blood flow (GMBF) measured with an endoscopic laser Doppler flowmetry in 27 healthy volunteers. They were randomly assigned to receive an endoscopic gastric submucosal injection (0.5 ml) of physiological saline (control group,N=10), 50 g of dopamine (DA) hydrochloride (N=8), and 500 g of a DA antagonist, metoclopramide (MCP) (N=9). The drugs were dissolved in the same saline volume (0.5 ml) as used in control group and were injected via the mucosal area where the baseline GMBF was measured and the postdose GMBF was monitored until 5 min postdose. There was no significant difference in the mean (±sem) baseline laser Doppler signals among the control, DA, and MCP groups (92.6±9.3, 81.8±9.0 and 96.9±13.3 mV, respectively). In the control group, no significant postdose changes in the laser Doppler signals occurred until 5 min postinjection. In contrast, the DA group exhibited a significant (P<0.05 or 0.01) increase in the laser Doppler signals at 2, 3, 4, and 5 min postdose (118.9±18.8, 128.5±16.9, 146.6±18.6, and 131.2±14.2 mV, respectively), whereas the MCP group exhibited a significant (P<0.05 or 0.01) decrease in the signals at 4 and 5 min postdose (67.9±5.3 and 64.8±3.5 mV, respectively), as compared not only with the respective baseline values but also with those obtained from other two groups at the corresponding postinjection periods. There was a significant (P<0.001) and negative correlation (r=–0.94) between the predose laser Doppler signals and their corresponding postinjection changes in the MCP group. Our data suggest that a tonic, dopaminergic stimulation may play a role in maintaining the GMBF in humansin vivo.This study was supported by grant-in-aids from the Ministry of Human Health and Welfare, Tokyo, and from the Pathophysiology Research Institute, Tokyo.     

Superficial blood flow, blood volume, and blood velocity in colorectal tubular adenomas and adenocarcinomas

To clarify differences in the vasculature of benign and malignant colorectal tumors, we compared blood flow (which has been examined in previous studies) as well as blood volume and blood velocity in two types of human colorectal tumors. We measured blood flow and blood volume with an endoscopic laser-Doppler flowmeter in the lesions and the normal mucosa near the lesions of 79 tubular adenomas with mild dysplasia and 38 adenocarcinomas. Blood velocity was defined as blood flow per blood volume. The ratio of each value in the lesions to that in the neighboring normal mucosa was defined as the relative value, and the mean relative values in the two groups were compared. The relative blood flow was 1.89 ± 0.64 in the tubular adenomas and 1.49 ± 0.66 in the adenocarcinomas (P < 0.005), and the relative blood volume was 1.10 ± 0.14 and 0.90 ± 0.13, respectively (P < 0.001). The relative blood velocity was approximately 1.7 in both groups (NS). This study demonstrated that the superficial blood flow in adenocarcinomas is increased due to increased blood velocity, despite blood volume being decreased. Received: July 17, 1998 / Accepted: January 22, 1999     

Role of mucosal blood flow in duodenal ulcer formation induced by dulcerozine

To clarify the role of mucosal blood flow in the pathogenesis of ulcer formation, the authors investigated dulcerozine-induced duodenal ulcers in rats. Administration of dulcerozine, 500 mg/kg by intragastric route or 250 mg/kg given intraperitoneally, induced acute ulcers in the duodenum, but not the stomach, in all rats. Using the pyloric ligation method, it was determined that although dulcerozine significantly increased gastric acid secretion, no duodenal ulcers were observed in these animals. The administration of 1 ml of 0.1 N HC1 every hour for 6 hours did not induce duodenal ulceration. The mucus glycoprotein content of the corpus, antrum and proximal duodenum did not differ following dulcerozine administration. Duodenal mucosal blood flow, which was measured by an electrolytically generated hydrogen gas clearance technique, decreased significantly following dulcerozine administration even in pylorus-ligated rats. In contrast, there was an increase in the gastric mucosal blood flow following administration of the drug. Therefore, not only an increase in gastric acid secretion but also a decrease in duodenal mucosal blood flow are suggested to be responsible for dulcerozine-induced duodenal ulceration.     

New method of evaluating gastric mucosal blood flow by ultrasound

Objective. Evaluation of gastrointestinal blood flow is important. However, a non-invasive measurement method has not yet been established. The aim of this study was to compare measurement of normal gastric mucosal blood flow by advanced dynamic flow (ADF) flash echo imaging (FEI) with intravenous Levovist with measurement by laser Doppler flowmetry (LDF) to clarify the usefulness of ADF-FEI and thereby consider its feasibility as a non-invasive gastric mucosal blood flow measurement method. Material and methods. Measurements were obtained in 25 beagle dogs (8-month-old males, body-weight, 10.6±1.3 kg, mean±SD). After insertion of a gastrointestinal endoscope, gastric mucosal blood flow at the greater curvature of the corpus was measured by LDF, and images of gastric mucosal blood flow were obtained by ADF-FEI (frequency; 4.7 MHz) with intravenous injection of Levovist (30 mg/kg). ADF-FEI images were transferred to a personal computer. A region of interest was set on the mucosa of the greater curvature of the corpus, and a time intensity curve (TIC) was plotted from the measured echo intensities. The area under the curve (AUC) calculated from the TIC and the median flow determined by LDF were analyzed and compared. Results. Evaluation of normal gastric mucosal blood flow by ADF-FEI was possible in all animals. There was a strong, significant correlation between gastric mucosal blood flow measured by LDF and the AUC obtained by ADF-FEI (r=0.869, p<0.0001). Conclusions. Gastric mucosal blood flow can be accurately measured by ADF-FEI with intravenous Levovist injection.     

Impaired vasoconstriction of peripheral cutaneous blood flow in Type 1 diabetic patients following food ingestion

Abnormalities in cutaneous blood flow (CBF) in otherwise healthy subjects with Type 1 diabetes mellitus (DM) have been demonstrated in response to local insults to the skin. To investigate whether defects also occurred in response to a regular daily activity, CBF was measured with laser Doppler flowmetry (LDF), before and 20 min after starting a mixed meal in 13 male Type 1 DM subjects with no clinical evidence of neuropathy, nephropathy or macroangiopathy and compared to 7 non-diabetic controls. Diabetic subjects and controls were of similar age and body mass index (mean ± SD, 33.7 ± 7.4 vs 37.1 ± 9.2 years and 25.2 ± 2.9 vs 24.5 ± 2.9 kg m⁻², respectively). In subjects with DM, HbA_1c was 8.3 ± 0.6 % (normal range 4–5.5 %) and duration of diabetes was 18 (8–38) years, median (range). Following a mixed meal the CBF fell in the controls by 36 % (24 to 56), median (range), compared to 3 % (−5 to 18) in Type 1 DM subjects, P < 0.0005. These results show there is a normal physiological fall in CBF following food ingestion which is attenuated in Type 1 DM. These abnormalities of vasoconstriction in the peripheral microcirculation are present after 8 years of diabetes and precede the development of clinically apparent neuropathy or vascular disease. © 1998 John Wiley & Sons, Ltd.     

Effect of natural peptide YY on blood flow and exocrine secretion of pancreas in dogs

Little is known regarding the mechanism by which peptide YY exerts an inhibitory effect on exocrine pancreatic secretion. The purpose of this study is to determine if peptide YY affects pancreatic blood flow with simultaneous measurement of exocrine pancreatic secretion in dogs. Pancreatic blood flow was measured by a laser Doppler flowmeter which allows continuous measurement of tissue blood flow. Natural peptide YY (0.1, 0.5, 1g/kg) was infused intravenously as a bolus under background infusion of secretin (1 unit/kg/hr) in combination with cholecystokinin-octapeptide (0.1g/kg/hr). Peptide YY caused a reduction of pancreatic blood flow in a dose-dependent manner as well as inhibition of pancreatic protein output, attaining the maximal reduction (28±4%) and inhibition (45±9%) at a dose of 1 g/kg, respectively. Simultaneous and continuous observation on tissue blood flow and exocrine secretion of the pancreas revealed that there was a highly significant correlation between the percent reduction of pancreatic blood flow and that of volume of pancreatic juice in response to peptide YY (r=0.849, P < 0.001). This study provides evidence that the mechanism of peptide YY-induced inhibition of exocrine pancreatic secretion is mediated, at least partly, through the decreased pancreatic blood flow.This study was supported by a grant from the Ministry of Education, Japan (A,61440060).A portion of this work was presented at the American Gastroenterological Association Meeting in New York in May 1985.     

Noninvasive measurement of portal venous blood flow in patients with cirrhosis

The present study aims to evaluate the usefulness of combined pulse Doppler-real-time ultrasonography as a noninvasive method for the measurement of portal blood flow in man. This measurement technique was performed on 12 healthy subjects and 20 patients with portal hypertension. Ten patients (group 1) were evaluated prior to and after ingestion of a standard meal (Ensure Plus) or placebo. In the remaining 10 patients (group 2), the effects of isosorbide dinitrate (5 mg/SL) administration or placebo were studied. In group 1, food intake caused a significant increase of portal blood flow (from 1038±539 to 1572±759 ml/min,P<0.02); this effect was due to a significant rise in mean blood velocity (from 18.5±3.7 to 23.9±3.9 cm/sec,P<0.02). In group 2, isosorbide dinitrate significantly reduced portal blood flow (from 985±491 to 625±355 ml/min,P<0.05); a significant decline of mean blood velocity (from 18.8 ±4.5 to 14.5±2.5 cm/sec,P<0.02) was observed. Placebo administration had no significant hemodynamic effects in either group. Our results suggest that Doppler measurements gave accurate noninvasive estimations of portal blood flow and that this technique may be used to monitor physiological and pharmological stimuli in patients with portal hypertension.     

Stimulation of gastric acid secretion increases mucosal blood flow in immediate vicinity of parietal cells in baboons

In acute experiments carried out in 27 baboons under general anesthesia, the regional gastric mucosal and muscle layer blood flow and gastric acid secretion were measured during 4 hr. Baboons were allocated to each of the following six groups: control, gastric acid stimulation with histamine 40 g/kg/hr intravenous, inhibition of basal or stimulated acid secretion with either ranitidine 50 mg intravenous or omeprazole 1 g/kg/hr. There were no significant cardiovascular alterations during the experiments. Histamine stimulation produced a concomitant rise in acid secretion and increase in blood flow only to the mucosal layer of the parietal-cell-bearing area of the stomach. Neither the underlying muscle layer nor the non-parietal-cell-bearing fundic or antral mucosa took part in this response, suggesting that a mechanism controlling blood flow is present in close proximity to the parietal cells. It was also established that the increase in blood flow occurs in response to parietal cell activity and not as a result of the action of histamine on the vascular system. Suppression of both basal and stimulated acid secretion did not cause a fall of mucosal blood flow below basal levels in any part of the stomach, indicating that drugs that inhibit parietal cell activity can be used in conditions where gastric mucosal ischemia should be avoided.Supported by South African Medical Research Council and Swiss National Foundation grant 3.846.0.83.     

Somatostatin reduces gastric mucosal blood flow in patients with portal hypertensive gastropathy

Agents which decrease gastric mucosal blood flow (GMBF) are postulated to have beneficial effects in arresting gastrointestinal bleeding in cirrhotic patients with portal hypertension. Our objective was to test the hypothesis that in a dose that significantly lowers wedged hepatic venous pressure (WHVP), a bolus injection of somatostatin will significantly decrease GMBF in patients with portal hypertensive gastropathy (PHG). In this placebo-controlled, double-blind, crossover study, 20 cirrhotic patients with PHG were randomly assigned to receive either somatostatin followed by placebo (Group A) or placebo followed by somatostatin (Group B). Wedged hepatic venous pressure was monitored. GMBF in the antrum and corpus was assessed by reflectance spectrophotometry. Indices of hemoglobin concentration (IHb) and indices of oxygen content (ISO₂) were recorded. Nine patients were assigned to Group A, and 11 to Group B. Mild PHG was seen in 16 patients, and severe PHG in 4 patients. Baseline WHVP, IHb, and ISO₂ were similar in both treatment groups. Wedged hepatic venous pressure (WHVP) was significantly lowered [median, 17.6%; interquartile range (–27.0, –12.6%); P=0.0008] after a 250-µg bolus injection of somatostatin. This dose of somatostatin significantly reduced IHb both in the antrum [–10.2% (–23.4, 0.4%)] and in the corpus [–5.8% (–16.6, 5.6%)] compared to placebo (P=0.02 and 0.04, respectively). Intravenous bolus injection of 250 µg somatostatin significantly reduces WHVP and GMBF in patients with PHG. Whether this ability to decrease the GMBF in PHG makes somatostatin an effective treatment in acute gastrointestinal bleeding in PHG deserves to be studied.     

Role of gastric mucosal blood flow in gastroprotective effect of novel xanthine derivative

The effect of 3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine (A90 6119) on 40% ethanol-induced gastric lesions and gastric mucosal blood flow was investigated in rats. Gastric mucosal blood flow was measured by the hydrogen gas clearance technique and the test compounds and vehicle were administered intraduodenally. A90 6119 dose-dependently increased gastric mucosal blood flow and decreased gross and histologic gastric mucosal injury induced by 40% ethanol. Both the gastric mucosal blood flow and protective effects of A90 6119 were completely attenuated by pretreatment with indomethacin. The findings demonstrate that A90 6119 protects against ethanol-induced gastric injury, and this effect involves stimulation of endogenous prostaglandin synthesis and an increase in gastric mucosal blood flow.This work was supported by a grant from Hoechst Japan Ltd., Veterans Administration Research Funds, and the facilities and expertise of the Blood Flow Core of the Center for Ulcer Research and Education.     

Assessment of blood flow in the small intestine by laser Doppler flowmetry: Comparison of healthy small intestine and small intestine in Crohn's disease

Blood flow and blood distribution were investigated in 40 patients with normal small intestine and the relation between blood flow and the morphological features of Crohn's disease was examined in 11 patients with Crohn's disease by laser Doppler flowmetry from the serosal side during surgery. In normal small intestine, blood flow was measured at six points: upper, middle, and lower small intestine, each of the mesenteric borders, and the antimesenteric surface. In Crohn's disease, macroscopically normal tissue and affected lesions were observed in detail by intraoperative endoscopy after blood flow measurement. The blood flow values in the normal small intestine gradually decreased from the upper to the lower small intestine. As the level of inflammation progressed in Crohn's disease the blood flow values gradually decreased; the exudative stage of Crohn's disease (aphthoid ulcer) showed blood flow values that were slightly below those in macroscopically normal tissue. These results are the first to demonstrate decreased blood flow in affected lesions in Crohn's disease and changes in blood flow according to the degree of inflammation in vivo.     

Absolute volumetric coronary blood flow measurement with digital subtraction angiography

The problems associated with visual interpretation of coronary arteriograms have been well-documented. There is a need for more physiologic means of assessing coronary artery stenosis during routine coronary arteriography. Volumetric coronary blood flow assessed as a function of time can be a valuable aid in the analysis of functional significance of arterial obstruction. A volumetric coronary blood flow measurement technique was investigated in a swine animal model using phase matched temporal subtraction images. The left anterior descending (LAD) coronary artery of swine animal models were instrumented with an ultrasound flow probe (US) and a vascular occluder producing stenosis. Contrast material injections (2–4 ml/sec for 3 sec) were made into the left coronary ostium during image acquisition. Phase-matched temporal subtraction (DSA) images were used to measure volumetric coronary blood flow in the LAD. In addition, a technique for automatic estimation of iodine calibration slope was also investigated. In 49 independent comparisons, the mean coronary blood flow (FPA) correlated extremely well with the mean US flow (FPA = 0.92US + 1.42 ml/min, r = 0.99, standard error of estimate (SEE) = 4.32 ml/min). Further more, the automatic iodine calibration technique was shown to be very accurate. In conclusion, accurate volumetric coronary blood flow measurements can be made before the onset of significant changes in coronary blood flow due to contrast injection.     

Ethanol-induced gastric mucosal blood flow and vascular permeability changes in the rat

Ethanol-induced gastric mucosal injury is accompanied by complete cessation of blood flow in the lesion area. An in vivomicroscopy technique was used in the rat to determine whether this cessation of blood flow could be due to increased microvascular permeability with marked plasma exudation and a resultant increase in blood viscosity. The topical application of 100% ethanol to the mucosa caused complete stasis of mucosal blood flow within 1 min. Fluorescent in vivomicroscopy revealed that topical ethanol also caused a prompt increase in mucosal microvascular permeability to albumin. This, however, did not explain the slowing and cessation of mucosal microvascular blood flow as these preceded the permeability change.This work was supported by NIAMDD grant AM 25891 and Veterans Administration Research Funds.     

Pathways mediating pentagastrin-induced mucosal blood flow response in rat stomachs

The mechanisms of pentagastrin-induced gastric mucosal blood flow (GMBF) response were investigated in anesthetized rats. A rat stomach was mounted on anex vivo chamber, perfused with saline, and GMBF was measured by a laser Doppler flowmetry simultaneously with acid secretion. Pentagastrin infused intravenously produced a dose-dependent increase of GMBF as well as acid secretion, and its effect reached a maximum at 120 µg/kg/hr (maximal dose). Pretreatment with omeprazole (60 mg/kg, intraperitoneally) completely inhibited the acid secretory response and the enhancement of GMBF induced by both submaximal (60 µg/kg/hr) and maximal doses of pentagastrin. In contrast, the luminal perfusion with glycine (200 mM) to remove luminal H⁺ almost totally attenuated the increase of GMBF caused by the submaximal dose of pentagastrin, without any effect on acid secretion, but partially suppressed such GMBF responses caused by the maximal dose. Subcutaneous pretreatment with indomethacin, a cyclooxygenase inhibitor, significantly mitigated GMBF response caused by both submaximal and maximal doses of pentagastrin, whereas 8-phenyltheophylline (8-PT), an adenosine antagonist, showed a significant inhibition of GMBF response caused by only the maximal dose. However, the combined administration of 8-PT with glycine perfusion further attenuated GMBF response caused by the maximal dose of pentagastrin, and the additional treatment with indomethacin completely blocked this GMBF response. We conclude that pentagastrin-induced GMBF responses are mediated by at least two different pathways; one is related to luminal H⁺ and the other to the parietal cell activity, depending on the dose of pentagastrin. In addition, the latter pathway may be mediated by adenosine, while endogenous prostaglandins may be involved in both pathways.     

肠生物反馈对孤立性直肠溃疡综合征患者直肠黏膜血流的影响

目的研究孤立性直肠溃疡综合征(solitary rectal ulcer syndrome,SRUS)患者的直肠黏膜血流变化,并分析肠生物反馈对SRUS患者症状及直肠黏膜血流的影响.方法16例SRUS患者及20例正常对照组,于生物反馈治疗前后分别采用激光多普勒血流计检测16例SRUS患者的直肠黏膜血流量,同时采用标准问卷表分别记录治疗前后症状变化.结果16例中有12例(75%)自觉症状缓解;16例中有5例(31%)结肠镜检查示溃疡愈合;治疗前SRUS患者直肠黏膜血流量明显低于正常对照组(P＜0.01),生物反馈治疗后,治疗组直肠黏膜血流量明显上升(P＜0.01),其中自觉症状缓解者直肠黏膜血流量增加尤为显著(P=0.001).结论肠生物反馈是一种治疗SRUS患者的有效行为疗法,其治疗效果与直肠黏膜血流的增加有关.