Impaired gastric mucosal energy metabolism in congestive gastropathy in cirrhotic patients

To clarify the characteristics of congestive gastropathy, we investigated gastric mucosal hemodynamics and energy metabolism in cirrhotic patients, using a reflectance spectrophotometry system and high performance liquid chromatography. The index of the gastric mucosal blood volume of cirrhotic patients with esophageal varices was significantly higher, and the index of gastric mucosal blood oxygenation significantly lower, than those in controls, thus indicating congestion and hypoxia in the gastric mucosa. Energy charge levels in the gastric mucosa of cirrhotic patients with esophageal varices were also significantly decreased. The energy charge level showed a strong linear correlation with the index of mucosal blood oxygenation in the antral (r=0.996,P<0.01) and body (r=0.994,P<0.01) mucosa of the stomach. These findings suggest that congestive gastropathy in a portal hypertensive state causes hypoxia in the gastric mucosa, leading to a mucosal energy deficit that may increase mucosal susceptibility to aggressive factors.     

垂体后叶素对门脉高压性胃病胃粘膜灌注的影响

目的 探讨垂体后叶素对门脉高压性胃病（ＰＨＧ）大鼠胃粘膜血流量（ＧＭＢＦ）和血浆胰高粘素的影响。方法 部分结扎大鼠门脉主干２ｗｋ后,采用激光多普勒血流计（ＬＤＦ）测定大鼠ＧＭＢＦ,观察了垂体后叶素输注前和输注后３０ｍｉｎ ＧＭＢＦ,门脉压力（ＰＶＰ）的变化;测定了输注垂体后叶素３０ｍｉｎ后血浆胰高糖素的含量。结果 输注垂体后叶素１０ｍｉｎ ＰＨＧ大鼠的ＧＭＢＦ开始降低（Ｐ〈０．０５）,１５ｍｉｎ显     

肝硬化门脉高压性胃病患者胃粘膜炎症与一氧化氮合酶表达

目的 定位、定量研究肝硬化门脉高压性胃症（ＰＨＧ）患者胃粘膜炎症及其与一氧化氮合酶（ｉＮＯＳ／ｃＮＯＳ）表达的关系。方法 肝硬化患者６０例,其中伴有ＰＨＧ者３５例,无胃粘膜病变者２５例。胃粘膜活检３块,Ｂｏｕｉｎ固定,ＨＥ染色及免疫组化ＳＰ法ＭＰＶ显微分光光度计测定ｉＮＯＳ／ｃＮＯＳ表达。结果 肝硬化ＰＨＧ发生率５８．２％,其中７１．４％患者伴有胃粘膜炎症（Ｐ〈０．０５）;胃粘膜炎症者胃粘膜血管ｉ     

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.     

慢性重型肝炎伴胃粘膜病变及门脉高压性胃病的研究

目的　观察慢性重型肝炎患者上消化道粘膜病变特点。方法　将列入观察对象的患者分为 2个组 :A组为肝硬化伴门静脉高压转重而符合慢性重型肝炎诊断者 ;B组为慢性肝炎病情转重者。同期住院的急性黄疸型肝炎病人作为对照观察。结果　A组慢重肝患者有 68 6% ( 13 1/ 191)胃体粘膜出现门脉高压性胃病 (PHG)改变 ;B组PHG为 2 4 6% ( 43 / 175 ) (P <0 0 5 ) ;A组胃粘膜病变 (GML)的检出率为 42 4% ( 81/ 191) ,与B组的45 1% ( 79/ 175 )无明显差异 (P >0 0 5 ) ;但与对照组相比差异显著 (P <0 0 1)。结论　重度PHG的发生与肝脏功能密切相关。门脉压变化影响胃粘膜微循环 ,对PHG形成有一定作用。慢性重型肝炎发生GML构成多脏器功能损伤表现之一。其发生机制可能与凝血因子合成障碍 ;门脉高压的作用 ;高胃泌素血症 ;肿瘤坏死因子(TNF)的作用有关。多种因素中某一因素可能在某一时期起主导作用。临床应重视整体治疗 ,如积极的支持疗法 ,改善肝功 ,补充凝血因子 ,纠正低氧血症 ,调节酸硷平衡。出现消化道症状及时进行胃镜检查 ,针对性处理     

Effects of loxoprofen sodium, a newly synthesized non-steroidal anti-inflammatory drug, and indomethacin on gastric mucosal haemodynamics in the human

Abstract Non-steroidal anti-inflammatory drugs (NSAID) are, and have been, frequently used for alleviation of pain in patients; however, they are known to cause gastric mucosal injury in experimental animals and in humans. A decrease in the gastric mucosal blood flow also plays an important role in the aetiology of acute gastric mucosal injury, as we previously reported. This study investigated the effect of a newly synthesized NSAID, loxoprofen sodium (sodium 2[p-2 oxocyclopentylmethyl) phenyl]propionate dihydrate, on gastric mucosal haemodynamics using a reflectance spectrophotometry system. Both single and cross-over methods were used in five volunteer subjects. Loxoprofen sodium 60 mg (one tablet) or indomethacin 25 mg (one tablet), was diluted in 10 mL water at 25°C and sprayed on the gastric mucosa via a polyethylene tube inserted into the biopsy channel of an endoscope. After drug administration, reflectance spectra were taken every 5 min for 30 min. The indices of mucosal haemoglobin content (IHb) and oxygen saturation of haemoglobin (ISO₂) were determined by the method previously reported by the authors. Indomethacin administration produced a significant decrease in both IHb and ISO₂ values, indication ischaemia. Loxoprofen sodium, however, showed no significant differences in either of the parameters. Haemorrhagic erosions were evident after indomethacin administration, but none were found after loxoprofen sodium administration. The conclusion reached on the basis of this evidence is that one-time topical application of loxoprofen sodium is safer than indomethacin.     

Gastric mucosal blood flow and hepatic perfusion index in patients with portal hypertensive gastropathy

Endoscopic laser Doppler velocimetry is a simple non-invasive method to measure gastric mucosal blood flow. The present study is an attempt to determine a correlation, if any, between gastric mucosal blood flow and the hepatic perfusion index in patients with portal hypertensive gastropathy and their relationship to the severity of liver disease. Thirty patients with portal hypertensive gastropathy due to cirrhosis of the liver (eight class A, 13 class B, nine class C, according to Child-Pugh Classification) and six normal subjects were recruited into the study. In all subjects, the gastric mucosal blood flow and venous vasomotor reflex response was measured at two sites: the lesser and greater curvature, using endosoopic laser Doppler velocimetry. The hepatic perfusion index was measured using dynamic liver scintigraphy. The hepatic perfusion index (ratio of arterial/portal venous perfusion) in normal subjects and patients with portal hypertensive gastropathy belonging to Child-Pugh class A, B and C were 0.36 ± 0.02, 0.53 ± 0.08, 0.62 ± 0.14 and 1.04 ± 0.28, respectively. The gastric mucosal blood flow was similar in Child's A, B and C cases, while the venous vasomotor reflex response was reduced according to the Child-Pugh score (Child's A 37.4 ± 5.4%, normal control 62.3 ± 10.9%, Child's B 38.3 ± 18.2%, Child's C 22.5 ± 15.2%) and was statistically significant. The gastric mucosal blood flow and hepatic perfusion index are inversely correlated. The hepatic perfusion index altered with grading of cirrhotic change. This study confirms that the severity of portal hypertensive gastropathy is correlated with Child-Pugh score.     

善得定对门静脉高压性胃病大鼠胃粘膜灌注的影响

目的 观察善得定对门静脉高压性胃病（ｐｏｒｔａｌ ｈｙｐｅｒｔｅｎｓｉｖｅ ｇａｓｔｏｐａｔｈｙ,ＰＨＧ）大鼠胃粘膜血流最（ｇａｓｔｒｉｃ ｍｕｃｏｓａｌ ｂｌｏｏｄ ｆｏｗ,ＧＭＢＦ）的影响,并对其作用机制作初步探讨。方法 部分结扎大鼠门静脉主干２周后,观察善得定对ＰＨＧ大鼠全身血流动力学,ＧＭＢＦ,门静脉压力（ＰＶＰ）的影响,测定了输注善得定３０ｍｉｎ后ＰＨＧ大鼠血浆胰高糖素,血浆和胃粘膜ＮＯ     

Indomethacin-induced changes in canine gastric mucosal haemodynamics and haemoglobin oxygenation, and the effects of topical anti-ulcer agents

Abstract Changes in gastric mucosal haemoglobin concentration (mucosal blood volume), mucosal haemoglobin oxygenation, mucosal blood flow and gastric arterial blood flow caused by indomethacin, an ulcerogenic agent, and anti-ulcer agents were investigated in the stomach flap of anesthetized dogs. Indices of mucosal haemoglobin concentration and haemoglobin oxygenation, mucosal blood flow and arterial blood flow to the stomach flap were measured simultaneously. The intravenous injection of indomethacin (10 mg/kg) caused an immediate decrease in mucosal haemoglobin concentration with a gradual decrease in mucosal and arterial blood flow, and a slight decrease in mucosal haemoglobin oxygenation. The topical application of prostaglandin E₂ (10 μg/ml) and spizofurone (a new anti-ulcer agent, 1 mg/ml) to the mucosa significantly increased these parameters, and remedied the decreases of these parameters caused by indomethacin. Cimetidine (20 mg/ml), pirenzepine (10 mg/ml) and proglumide (40 mg/ml) given topically did not significantly increase these parameters in the resting state or the indomethacin-induced ischaemic state. This study indicates that: indomethacin decreases gastric haemodynamics, and that improvement occurred with application of mucosal protective agents (i.e. prostaglandin E₂ and spizofurone) and changes in mucosal blood concentration were closely correlated with those in mucosal blood flow and arterial blood flow, but correlated less well with those in the case of haemoglobin oxygenation.     

Ethanol-induced gastric mucosal damage in the rat with Taenia-stimulated hypertrophic gastropathy

The susceptibility to ethanol-induced lesions was studied in rats with experimental hypertrophic gastropathy, in order to examine the nature of gastric mucosal resistance in this condition. Acute erosions were induced by a standard per os method of administration with graded concentrations of ethanol; underlying mucosal hypertrophic gastropathy was induced by infection with Taenia taeniaeformis. The gastric mucosal content of histamine and serotonin was also assessed. Hypertrophic gastropathy was characterized by mucus cell hyperplasia, greatly increased stomach weight, increased mucosal content of histamine, and no effect in resistance to gastric injury induced by graded doses of ethanol. Correlated changes in serotonin content with treatment were not observed, but mucosal histamine content was correlated inversely with ethanol administration in both parasite-infected and non-infected rats. This model of hypertrophic gastropathy could be of interest to study the pathogenesis of hypertrophic gastropathy and its response to known injurious agents.     

The effects of a prostaglandin E1 analogue, misoprostol, on gastric mucosal blood volume index and haemoglobin oxygenation in humans

A double-blind placebo-controlled parallel design study was conducted in 12 healthy male volunteers to examine the effects of misoprostol, a newly synthesized prostaglandin E₁ analogue, on gastric mucosal haemodynamics in human. The indices of mucosal blood volume (expressed as ΔEr) and mucosal blood haemoglobin oxygenation (Hb-SO₂) were measured at 20 locations in the stomach prior to and after administration of misoprostol or its placebo using reflectance spectrophotometry during endoscopy. It was found that after misoprostol administration, mucosal blood volume was increased by approximately 10–25% throughout the stomach without any significant change in mucosal blood Hb-SO₂. Administration of placebo produced no significant change in these parameters. The results suggest that misoprostol has the potential to accelerate healing of gastric ulcers by increasing the gastric mucosal blood volume and oxygenation in addition to its gastric acid antisecretory activity.     

Comparison of the efficacy of octreotide,vasopressin, and omeprazole in the control of acute bleeding in patients with portal hypertensive gastropathy: a controlled study

BACKGROUND: Portal hypertensive gastropathy is an important complication of liver cirrhosis and it contributes to acute gastric bleeding. Effective management of this condition remains a clinical challenge. We assessed and compared the efficacy of octreotide, vasopressin, and omeprazole in the treatment of acute bleeding in patients with portal hypertensive gastropathy. METHODS: Sixty-eight patients with portal hypertensive gastropathy were randomized into Octreotide, Vasopressin, and Omeprazole groups. Bleeding was monitored by observing the contents of the nasogastric tube. Blood transfusion requirements and side-effects of drugs were recorded. Repeat endoscopies were scheduled 2 weeks after treatment. RESULTS: Complete bleeding control after 48 h of drug infusion was achieved in all patients receiving octreotide (100%), 14/22 patients receiving vasopressin (64%), and 13/22 patients receiving Omeprazole (59%). Octreotide required much less time and significantly fewer blood transfusions to control bleeding. Patients receiving vasopressin experienced more side-effects than those receiving octreotide and omeprazole. In the 17 patients whose bleeding was not controlled within 48 h by either vasopressin or omeprazole, complete bleeding control was achieved by combined use of these two agents. Follow-up endoscopy showed dramatic improvement in gastric mucosal erosions, superficial ulceration and erythema. CONCLUSIONS: Octreotide appeared to be more effective in controlling acute bleeding in patients with hypertensive gastropathy, with significantly rapid action, smaller transfusion requirements, and minor side-effects. Simultaneous administration of vasopressin and omeprazole appeared to have additive effects.     

Effects of propranolol on gastric mucosal perfusion and serum gastrin level in cirrhotic patients with portal hypertensive gastropathy

Gastric mucosal hyperemia associated with elevated serum gastrin level has been suggested in cirrhotic patients with portal hypertensive gastropathy (PHG). Clinical evidence has shown that these patients may benefit from propranolol administration. The aim of this study was to investigate effect of propranolol on gastric mucosal perfusion and serum gastrin level in cirrhotic patients with portal hypertensive gastropathy. Gastric mucosal perfusion was assessed by laser Doppler flowmetry. Measurements were performed under basal conditions and after observer-blind administration of propranolol (30–60 mg/day,N=9) or placebo (N=9) for seven days. Placebo had no effect on either gastric mucosal perfusion or serum gastrin level. In contrast, propranolol administration significantly decreased both antrum gastric mucosal perfusion (from 0.88±0.28 to 0.73±0.26 V,P<0.05) and corpus gastric mucosal perfusion (from 0.94±0.35 to 0.78±0.25 V,P<0.05). However, this drug had no effect on serum gastrin level. We conclude that chronic propranolol administration in cirrhotic patients with portal hypertensive gastropathy may reduce gastric mucosal perfusion without changing serum gastrin level.     

Effects of a gastric mucosal protecting agent in rats with liver cirrhosis

Male Sprague-Dawley rats were fed a 0.1% ethionine-added choline-deficient diet for 8 weeks to induce liver cirrhosis. At the same time 100 mg/kg/day teprenone was administered orally in order to evaluate its effects on the liver and gastric mucosal blood flow. Blood flow increased not only in gastric mucosa but also in liver tissues in the teprenone group. Serum transaminase levels and histopathologic findings of the liver also improved. These findings suggest that teprenone alleviates hepatocellular injuries. This effect may be partly attributable to cytoprotective effects of the catenoid isoprenoid moiety of teprenone on liver cells.     

一氧化氮和前列腺素在门静脉高压性胃病大鼠胃粘膜灌注中的作用

目的 探讨一氧化氮（NO）和前列腺素在门静脉高压性胃病（PHG）大鼠胃粘膜灌注中的作用。方法 部分结扎大鼠门静脉主干2周后,采用中性红清除率法测定大鼠胃粘膜血流量（GMBF）,同时观察门静脉压力（PVP）的变化。结果 PHG组大鼠GMBF和PVP显著高于假手术组（t=3.431、3．312,P＜0．01）。低剂量的NO合成酶抑制剂L－硝基－精氨酸甲酯（L－NAME）呈剂量依赖性降低PHG大鼠GMBF,而对假手术组GMBF无明显影响;高剂量的L－NAME（12mg/kg)能非常显著降低PHG和假手术组大鼠GMBF。前列腺素环氧合酶抑制剂消炎痛能明显降低PHG组大鼠GMBF,而对假手术组GMBF无明显影响;预先给消炎痛处理后在假手术组大鼠中,静脉注射低剂量L－NAME（4mg/kg)前后GMBF无明显变化,高剂量L－NAME（12mg/kg)降低大鼠的GMBF与未用消炎痛处理组比无明显变化;预先给消炎痛处理后在PHG组大鼠中,L－NAME剂量（4mg/kg、12mg/kg)依赖性降低大鼠的GMBF与未用消炎痛处理组比无明显改变。结论 NO、前列腺素在调节PHG大鼠的GMBF起重要作用,但两者无协同作用。     

Effect of hepatic collateral hemodynamics on gastric mucosal blood flow in patients with liver cirrhosis

The dependence of the gastric mucosal change in liver cirrhosis on the extrahepatic collaterals is still unknown. Therefore we studied the influence of these collateral hemodynamics on gastric mucosal blood flow and gastric mucosal lesions. The subjects were 23 cirrhotic patients and were divided into two groups by the findings of percutaneous transhepatic portography. The first group consisted of 14 cases whose extrahepatic collaterals were via esophageal varices (group I). The second group included 9 cases having collaterals other than esophageal varices (group II). Multiple red spots were observed in 13 of 14 cases in group I, and two of nine cases in group II. Gastric mucosal blood flow was 2.0±0.9 volts (mean±sd) in group I, 4.0±1.2 in group II. A statistically significant difference was observed between groups I and II. Gastric mucosal blood flow was not significantly correlated with portal venous pressure in group I. It is concluded that, in liver cirrhosis, gastric mucosal blood flow is changeable according to the types of the extrahepatic collaterals.     

Effect of laparoscopic splenectomy on portal hypertensive gastropathy in cirrhotic patients with portal hypertension

Aim:  This study investigated the relationship between portal hypertensive gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on PHG in cirrhotic patients with portal hypertension.
Methods:  Seventy patients with liver cirrhosis and portal hypertension were prospectively studied. Indication for laparoscopic splenectomy was bleeding tendency in 10 patients, induction of interferon in 45, treatment of hepatocellular carcinoma in seven, and treatment for endoscopic injection sclerotherapy-resistant esophagogastric varices in eight. The severity of PHG was classified into none, mild, or severe according to the classification by McCormack et al. The severity of liver disease was classified using the Child–Pugh score. All patients underwent upper gastrointestinal endoscopy before and 1 month after the operation.
Results:  The prevalence of PHG was significantly correlated with the severity of liver disease using the Child–Pugh score. The severity of PHG was significantly correlated with the resected spleen volume. One month after the operation, PHG was improved in 16 of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child–Pugh score showed a significant improvement (6.8 ± 1.4 to 6.2 ± 1.2) at 3 months after laparoscopic splenectomy ( P  < 0.0001).
Conclusions:  PHG may be associated with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on PHG, at least for a short time.     

Effects of ammonia solution on the gastric mucosa in cirrhotic rats and therapeutic effects of geranylgeranylacetone

BACKGROUND: We designed an animal model in order to clarify whether Helicobacter pylori infection causes the gastric mucosal lesion frequently seen in cirrhotic patients. METHODS: Ammonia (NH3) solution was given to rats with carbon tetrachloride-induced cirrhosis. The gastric mucosal hexosamine (Hx) content and histopathological findings in the cirrhotic rats were analysed and compared with those of the intact liver rats. Moreover, the usefulness of geranylgeranylacetone (GGA) was investigated in both rat groups. Both rat groups were subdivided according to the treatment as follows: a control group, an NH3 (0.02% solution) group, and an NH3 + GGA (400 mg/kg per day) group; and fed for 4 weeks. RESULTS: The gastric mucosal Hx content of the control group of the cirrhotic rats (16.7 +/- 5.2 microg/mg) was significantly lower than that of the control group of the intact liver rats (26.6 +/- 4.5 microg/mg, P < 0.05). In the cirrhotic rats, the Hx content of both the NH3 (31.9 +/- 13.1 microg/mg) and the NH3 + GGA group (31.9 +/- 9.8 microg/mg) was significantly higher than the Hx content of the control group (P < 0.05). Microscopically, in the cirrhotic rats, while scattered mucosal erosions were recognized in three of five rats of the NH3 group, there were no erosions in any rats of the NH3 + GGA group. CONCLUSIONS: These data suggest that the gastric mucosal defence mechanism is defective in liver cirrhosis and that NH3 enhances this defensive mechanism by acting as mild irritant; however, in some cirrhotics this results in gastric erosion due to excessive irritation. Geranylgeranylacetone protects the gastric mucosa against NH3 irritation in cirrhotics without enhancing the Hx content. Thus, H. pylori infection may be a possible cause of the gastric mucosal lesion in patients with liver cirrhosis. The mechanism of the therapeutic effect of GGA is not due to an enhancement of the gastric mucosal Hx content.     

Effects of electroacupuncture on gastric mucosal blood flow and transmucosal potential difference in stress rats

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