Biomedical subjects

M C Hou

Publications and source records attributed to M C Hou.

At least 37 records · Page 2Linked to original sources

PubMed1999

Moe1, a conserved protein in Schizosaccharomyces pombe, interacts with a Ras effector, Scd1, to affect proper spindle formation.

In fission yeast, Scd1/Ral1 is a putative guanine nucleotide exchange factor for Cdc42sp and also acts as a Ras1 effector necessary for the regulation of cytoskeleton organization. In this study, we have characterized a protein, Moe1, that binds directly to Scd1. A moe1 null (Delta) mutant exhibits numerous phenotypes indicative of abnormal microtubule functioning, including an abnormality in the spindle. moe1Delta mutants are resistant to microtubule destabilizing agents; moreover, moe1Delta rescued the growth defects of tubulin mutants containing unstable microtubules. These results suggest that Moe1 induces instability in microtubules. Biochemical and subcellular localization studies suggest that Moe1 and Scd1 colocalize in the nucleus. Furthermore, loss of function in Scd1 or Ras1 also induced abnormality in the spindle and is synthetically lethal with moe1Delta producing cells that lack a detectable spindle. These data demonstrate that Moe1 is a component of the Ras1 pathway necessary for proper spindle formation in the nucleus. Human and nematode Moe1 both can substitute for yeast Moe1, indicating that the function of Moe1 in spindle formation has been conserved substantially during evolution.

Carrier Proteins↗

PubMed1999

Effects of sustained-release lanreotide on hemodynamics in rats with portal vein stenosis.

BACKGROUND/AIMS: Somatostatin and its analogue have been shown to provide beneficial effects in the management of portal hypertension and hyperdynamic circulation. The current study was undertaken to evaluate the effects of lanreotide, a sustained-release somatostatin analogue, on hemodynamics in rats with portal hypertension. METHODS: Immediately after portal vein stenosis, rats were randomly assigned to receive vehicle or a single intramuscular injection of lanreotide 10 mg/kg. Hemodynamic measurements (radioactive microsphere technique) with portal systemic shunts determinations were performed on the 4th and 8th day after surgery, respectively. RESULTS: On the 4th day after surgery, rats treated with lanreotide had significantly lower cardiac index and higher systemic vascular resistance than rats treated with vehicle, while these values were no different on the 8th day after portal vein stenosis. In contrast, the elevation of portal pressure, portal tributary blood flow, and splanchnic fraction of cardiac output had ameliorated following lanreotide administration associated with an increase in splanchnic arterial resistance. Portal systemic shunts were lower in rats receiving lanreotide than in rats receiving vehicle. CONCLUSION: The current study showed that a single injection of sustained-release lanreotide in rats with portal vein stenosis delayed the development of peripheral arterial vasodilatation and hyperdynamic circulation, while it modified the evolution of portal hypertension and splanchnic hyperemia. This treatment also prevents, in part, the development of portal systemic shunts in rats with portal vein stenosis.

Animals↗

PubMed1999

Effect of anaemia on haemodynamics in patients with cirrhosis.

BACKGROUND: It has been suggested that increased blood haemoglobin attenuates splanchnic vasodilatation in portal-hypertensive rats by nitric oxide inactivation. However, the haemodynamic effect of anaemia in cirrhotic patients of varying severity has been rarely discussed. The aim of this study was to evaluate the influence of anaemia on systemic and splanchnic haemodynamics in cirrhotic patients of differing severity. METHODS: Two hundred and twenty-five cirrhotic patients were included in this study. All biochemical and haemodynamic results were utilized for analysis. Anaemia was defined as a haemoglobin level below the cut-off value of 12 g/dL, which might best predict low systemic vascular resistance. RESULTS: Compared with non-anaemic patients, anaemic patients had decreased mean arterial pressure (90 +/- 1 vs 95 +/- 1 mmHg, P = 0.002), and decreased systemic vascular resistance (1022 +/- 25 vs 1227 +/- 30, P < 0.0001), and increased cardiac index (4.3 +/- 0.1 vs 3.8 +/- 0.1 L/min per m2, P < 0.0001) and increased hepatic venous pressure gradient (16.7 +/- 0.5 vs 14.4 +/- 0.6 mmHg, P = 0.006). Haemoglobin concentration exerted an influence on the degree of vasodilatation in cirrhotic patients, with Child-Pugh's A class (but not in Child-Pugh's B and C classes), and in patients without ascites (but not in patients with ascites). CONCLUSIONS: It was concluded that anaemia has a negative effect on hyperdynamic circulation in patients with early cirrhosis which is not observed in patients with advanced cirrhosis.

Anemia↗

PubMed1999

The rebleeding course and long-term outcome of esophageal variceal hemorrhage after ligation: comparison with sclerotherapy.

BACKGROUND: Endoscopic variceal ligation is widely accepted as the optimum endoscopic treatment for esophageal variceal hemorrhage. However, the rebleeding course and long-term outcome of patients with esophageal variceal hemorrhage after ligation have been poorly defined. Therefore, we conducted a long-term follow-up study to delineate the outcome of ligation and compare it with that after sclerotherapy. METHODS: One hundred and eighty-five liver cirrhotic patients with endoscopically proven esophageal variceal hemorrhage were randomized to undergo endoscopic variceal sclerotherapy or ligation. These patients received regular follow-up and detailed clinical assessment. RESULTS: Two patients developed hepatoma within 6 months of entry in each group and were excluded. Another six patients in the sclerotherapy group and seven patients in the ligation group were excluded because of poor compliance or lost to follow-up. Therefore, 84 patients in each group were analyzed. In this long-term follow-up (55.3 +/- 12.5 months) the rebleeding rate for ligation was lower than that for sclerotherapy, regardless of whether the rebleeding was analyzed by patient number or Kaplan-Meier analysis. With regard to the rebleeding risk of various periods, the sclerotherapy risk was higher than that of ligation within 4 weeks of the initial endoscopic treatment or before variceal eradication. Multifactorial analysis showed hematemesis, poor hepatic function, and sclerotherapy were the risk factors determining rebleeding. The annual hepatocellular carcinoma incidence was 4.9%. There was no difference in survival between sclerotherapy and ligation. Multifactorial analysis showed that poor hepatic function was the only factor determining survival. CONCLUSIONS: The rebleeding risk was higher in sclerotherapy than in ligation before variceal eradication, especially within 4 weeks of the initial endoscopic treatment. Long-term survival was dependent on hepatic reserve regardless of the treatment method.

Chi-Square Distribution↗

PubMed1999

Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function.

BACKGROUND: Spider angioma is a common sign in patients with liver cirrhosis, but the pathogenesis is still unclear. Alcohol and hyperestrogenemia are both possible etiologies. This study was designed to investigate the relationship of spider angiomas in patients with liver cirrhosis to alcohol, liver function test results, and plasma levels of sex hormones. METHODS: Eighty-two patients with liver cirrhosis and 18 healthy subjects were enrolled in this study. The number, size, and location of the spider angiomas were recorded for all subjects. Plasma levels of estradiol and testosterone were measured. RESULTS: Cirrhotic patients had significantly higher estradiol/testosterone ratios (26.8 +/- 5.1 x 10(-3) versus 8.8 +/- 2.0 x 10(-3); P = 0.002) than healthy controls. Twenty-seven (33%) of the 82 cirrhotic patients had spider angiomas. Cirrhotic patients with spider angiomas were younger (56 +/- 3 versus 66 +/- 1 years; P = 0.002) and had higher serum bilirubin levels (3.3 +/- 0.6 versus 1.7 +/- 0.2 mg/dl; P = 0.002), longer prothrombin time (16.8 +/- 0.8 versus 14.8 +/- 0.4 sec; P = 0.01), and higher prevalence of alcoholism (41% versus 20%; P = 0.04) than those without. Stepwise logistic regression showed that alcoholism and serum bilirubin level were the only significant and independent predictors associated with the presence of spider angiomas in cirrhotic patients (odds ratio = 3.5; 95% confidence interval = 1.2-10.8; P = 0.03, and odds ratio = 2.8; 95% confidence interval = 1.3-5.7; P = 0.006, respectively). CONCLUSIONS: Alcoholism and impaired liver function are important predictors of the presence of spider angiomas in patients with liver cirrhosis.

Aged↗

PubMed1999

Serum uric acid levels in patients with cirrhosis: a reevaluation.

It has been reported that the serum uric acid levels in patients with cirrhosis were decreased compared with healthy subjects. These studies suggested that the lower serum uric acid levels in cirrhotic patients were attributed mainly to an increased effective vascular volume, and consequently to an excessive renal clearance of uric acid. However, the previous observations are challenged by a recent hypothesis for the pathogenesis of hyperdynamic circulation and formation of ascites in cirrhosis. The current study was undertaken to reevaluate serum uric acid levels in patients with cirrhosis. Ninety-eight cirrhotic patients with normal renal functions were included in this study. All biochemical and hemodynamic data were utilized for analysis. The mean serum uric acid level (mean, 6.1+/-1.2 mg/dL; range, 2.7-9.1 mg/dL) was higher than that of the age- and sex-matched healthy control subjects (mean, 5.5+/-1.3 mg/dL; range, 2.9-8.1 mg/dL; p = 0.018). Using multiple regression analysis it was determined that the serum uric acid level was not related to the severity of liver disease, cardiac index, systemic vascular resistance, and hepatic venous pressure gradient but was related closely to age (r = 0.210, p = 0.026) and effective renal plasma flow (r = -0.677, p < 0.0001). Compared with cirrhotic patients without ascites, those with ascites had a significantly higher serum uric acid level (6.7+/-1.6 mg/dL vs. 5.6+/-1.7 mg/dL, p < 0.05) and lower effective renal plasma flow (396+/-125 mL/min vs. 445+/-149 mL/min, p < 0.05). In conclusion, for cirrhotic patients with normal serum creatinine levels, the current study shows that the mean serum uric acid level is higher than that of healthy control subjects. It is not related to the severity of liver failure and systemic and portal hemodynamics, but is related closely to renal functions, especially the renal plasma flow.

Adult↗

PubMed1999

Supportive treatment, resection and transcatheter arterial chemoembolization in resectable hepatocellular carcinoma: an analysis of survival in 419 patients.

OBJECTIVE AND DESIGN: Both surgical resection and transcatheter arterial chemoembolization (TACE) are effective treatments for hepatocellular carcinoma (HCC). Few reports have compared the different treatment modalities for resectable HCC based on clinically matched groups. The aim of this study was to compare the survival rate after surgery, TACE or supportive treatment in resectable HCC patients, and also in elderly patients (> or = 70 y/o). METHODS: From 1984 to 1993, 419 consecutive patients with resectable HCC were included in this study. Of these, 311 (74%) underwent resection of tumours and 46 (11%) refused operation, opting instead for TACE. The remaining 62 (15%) who refused both methods of treatment were given supportive care. Univariate and multivariate analyses for prognostic factors and the 5-year survival rate among the groups were studied. RESULTS: Both surgical resection and TACE groups had a better 5-year survival rate than the supportive treatment group (43% and 34% vs. 7%). There was no difference in survival between the surgery and TACE groups. However, the 5-year survival rate was 11% in TACE and 41% in the surgical group when the patients were > or = 70. In multivariate analysis, female sex (P = 0.0466), tumour size < or = 3 cm (P = 0.0001), alpha-fetoprotein (AFP) < 400 U/l (P = 0.0036), single tumour (P = 0.0474), serum creatinine < or = 1.5 mg/dl (P = 0.0006) and alkaline phosphatase (AP) < or = 100 U/l (P = 0.0007) are associated with good prognosis for resectable HCC. CONCLUSION: TACE is an alternative for resectable HCC. Tumour size, tumour number, AFP level, renal function, AP level and female sex are prognostic factors. In elderly people, TACE must be used prudently and has a worse prognosis.

Age Factors↗

PubMed1999

Effects of octreotide on central hemodynamics and systemic oxygen use in patients with viral cirrhosis.

OBJECTIVE: Octreotide has potentially beneficial effects in patients with cirrhosis. However, the effects of octreotide on central hemodynamics and oxygen use have not been established. The present study was undertaken to evaluate the effect of octreotide on central hemodynamics and oxygen use in patients with viral cirrhosis. METHODS: Twenty-five patients with cirrhosis were enrolled in the study. They were randomly assigned to receive either placebo (n = 10) or a continuous infusion of 100 microg/h of octreotide after an initial 100-microg bolus (n = 15). Hemodynamic measurements and oxygenation values were obtained before and 60 min after octreotide or placebo administration. RESULTS: Placebo administration did not have any effect on hemodynamic and oxygenation values. In patients who received octreotide, systemic hemodynamic values including cardiac index, mean arterial pressure, and systemic vascular resistance were not affected. The mean pulmonary arterial pressure tended to increase after octreotide administration but was statistically insignificant. There was a significant increase in pulmonary arterial vascular resistance, whereas the pulmonary capillary wedge pressure and right atrial pressure were significantly decreased. Arterial oxygen tension, systemic oxygen uptake, and oxygen extraction ratio were significantly decreased after octreotide administration, whereas oxygen transport as well as arterial and mixed venous oxygen contents remained unchanged. CONCLUSIONS: In patients with viral cirrhosis, octreotide administration exerted a significant effect on pulmonary circulation. It also resulted in a decrease in systemic oxygen uptake and oxygen extraction ratio. These results suggested that octreotide may impair tissue oxygenation in patients with viral cirrhosis.

Aged↗

PubMed1999

Role of substance P in the pathogenesis of spider angiomas in patients with nonalcoholic liver cirrhosis.

OBJECTIVE: Cutaneous spider angioma is a common sign observed in patients with liver cirrhosis, but its pathogenesis is still unclear. Increased plasma levels of estrogen, vascular dilation, and neovascularization are possible etiologies. This study was designed to investigate the relationship of spider angiomas in patients with nonalcoholic liver cirrhosis to the plasma levels of sex hormones and various vasodilators and hemodynamic parameters. METHODS: A total of 60 patients with nonalcoholic liver cirrhosis and 20 healthy subjects were included in this study. The number, size, and location of the spider angiomas were recorded. Plasma levels of estradiol, testosterone, substance P, calcitonin gene-related peptide, and nitrate/nitrite and forearm hemodynamics were measured. RESULTS: Cirrhotic patients showed higher plasma estradiol/testosterone ratios (28.3+/-47.2 x 10(-3), median 10.5 x 10(-3) vs 8.2+/-8.3 x 10(-3), median 5.7 x 10(-3), p = 0.003) and levels of nitrate/ nitrite (29.9+/-17.5, median 23.8 vs 21.4+/-10.0, median 20.6 micromol/L, p = 0.01) and substance P (47.5+/-62.5, median 29.2 vs 15.2+/-7.7, median 12.3 pg/ml, p < 0.001) than healthy controls. Sixteen (27%) of the 60 cirrhotic patients had spider angiomas. Cirrhotic patients with spider angiomas disclosed higher plasma levels of substance P (84.7+/-105.3, median 53.1 vs 34.5+/-30.7, median 25.8 pg/ml, p = 0.006) and serum levels of bilirubin (3.9+/-3.8, median 1.9 vs 1.9+/-1.9, median 1.2 mg/dl, p = 0.02) than those without. Stepwise logistic regression showed substance P was the only significant and independent predictor associated with the presence of spider angiomas in cirrhotic patients (odds ratio = 3.0, 95% confidence interval = 1.4-6.6, p = 0.01). CONCLUSION: Plasma levels of substance P are elevated in patients with nonalcoholic cirrhosis and may play an important role in the pathogenesis of spider angiomas.

Aged↗

PubMed1999

Hemostatic changes in patients with liver cirrhosis.

BACKGROUND: Hemostatic changes in liver disease are complicated. An overall evaluation of the main hemostatic parameters in patients with different degrees of cirrhosis of the liver has not been reported in Taiwan. METHODS: A series of hemostatic tests and parameters including activated partial thromboplastin time, prothrombin time, thrombin time, bleeding time, factor VIII assay, antithrombin activity, fibrinogen, plasminogen, protamine sulfate test, fibrin(ogen) degradation products, D-dimer, thrombin-antithrombin complex (measured by modified antithrombin), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1, euglobulin lysis test and venous occlusion test were performed in 51 patients with cirrhosis of the liver and 33 healthy controls. Among the cirrhotics, 18 were classified as Child-Pugh group A, 16 were B and 17 were C. RESULTS: Plasminogen, antithrombin and platelet count decreased progressively, starting with group A, then B and then C, relative to the controls. Factor VIII, activated partial thromboplastin time, prothrombin time, bleeding time, D-dimer and fibrin(ogen) degradation products increased progressively starting with group A, to B and then C, relative to controls. Severity of cirrhosis correlated with hemostatic changes. No significant change in the fibrinolytic response after challenge with the venous occlusion test was found in either Child-Pugh groups A, B, C or the controls, though progressive increases in tPA were found starting with group A, to B and then C, relative to controls. CONCLUSIONS: Our study proved a close relationship between the severity of cirrhosis and hemostatic changes. Activated partial thromboplastin time was better than bleeding time or thrombin time to demonstrate the severity of liver damage and hemostatic change in cirrhosis. Because the deterioration of coagulation function and increased fibrinolytic activity paralleled the severity of liver cirrhosis, adequate treatment for cirrhotic bleeding should not only correct the coagulation defects, but should also lower the increasing fibrinolytic activity.

Adult↗

PubMed1998

Enhanced cyclooxygenase-1 expression within the superior mesenteric artery of portal hypertensive rats: role in the hyperdynamic circulation.

Portal hypertension (PHT) is characterized by splanchnic hyperemia due to enhanced production of vasodilator substances. Enhanced vasodilation and increased splanchnic blood flow contribute to the elevated portal pressure characteristic of PHT. The aim of this study was to determine whether cyclooxygenase (Cox) expression is altered in PHT vessels and whether chronic inhibition of this enzyme impacts on splanchnic blood flow in PHT. PHT was created in Sprague-Dawley rats by a partial portal vein ligation. Control animals were sham operated. Plasma 6-keto-PGF1alpha (prostaglandin F1alpha) levels were significantly elevated in PHT after 2 days as compared with sham and remained elevated up to day 15. Treatment with indomethacin (2 mg/kg i.p. daily for 15 days) resulted in a significant decrease in 6-keto-PGF1alpha levels, which was concomitant with a significant decrease in superior mesenteric artery blood flow (Qsma) after 15 days in PHT rats. Cox-I expression was differentially enhanced in the PHT superior mesenteric artery and thoracic aorta during the development and progression of PHT. In contrast, Cox-II messenger RNA (mRNA) and protein expression was not detected in either of these vessels throughout the development of PHT. These data suggest that PHT is associated with enhanced Cox-I expression within the splanchnic vasculature concomitant with elevated plasma prostacyclin levels and a significant pressor response to indomethacin in PHT animals. We conclude that enhanced Cox-I expression results in increased prostacyclin levels that partially contribute to the maintenance of the hyperemia typical of PHT.

Animals↗

PubMed1998

Increased expression of endothelin receptors in the vasculature of portal hypertensive rats: role in splanchnic hemodynamics.

Portal hypertension (PHT) is characterized by increased portal pressure caused in part by a reduction in mesenteric vascular resistance. The aim of this study was to evaluate the role of endothelin (ET) and specific ET receptors in maintaining the vasculopathy of PHT. PHT was created in Sprague-Dawley rats by a partial portal vein ligation. Control animals were sham-operated. ET receptor expression was determined in the superior mesenteric artery of sham and PHT rats by in situ autoradiography, radioligand binding analysis, and reverse-transcription polymerase chain reactions (RT-PCR). The pressor response to ET-1 was determined in vitro using isolated vascular rings and in vivo by measuring mean arterial pressure, splanchnic blood flow, and portal venous pressure following treatment with ET and selective ET receptor antagonists. The pressor response to ET in vitro was significantly enhanced in PHT concomitant with increased ET-A and ET-B receptor expression. There was a significant increase in the peak pressor response to ET (10 microg/kg intravenously) in portal hypertensive rats without any significant change in plasma ET-1 levels. There was no significant difference in the peak splanchnic blood flow or portal venous pressure response following ET-A receptor blockade with JKC-301 infusion (200 microg/kg intravenously). In contrast, ET-B receptor blockade with IRL-1038 (200 microg/kg intravenously) preferentially decreased splanchnic blood flow and portal venous pressure in portal hypertensive rats. These data suggest that enhanced ET-B receptor expression in portal hypertensive vessels contributes to the maintenance of elevated portal pressure in these animals.

Animals↗

PubMed1998

The relationship of Helicobacter pylori colonization, the serum pepsinogen A level, and gastric resection.

The serum levels of pepsinogen A (PGA) were measured in patients who underwent various forms of gastric resection to assess whether Helicobacter pylori (HP) colonization has any influence. Included in this study were 48 patients who underwent subtotal gastrectomy for a peptic ulcer (SGPU), 36 who underwent radical subtotal gastrectomy for gastric carcinoma (SGGC), 16 who underwent truncal vagotomy plus antrectomy (TV + AE), 24 with recurrent ulcer (RU) and 27 who underwent total gastrectomy (TG). The mean serum PGA levels in these five groups and in 40 healthy controls were 49.1 +/- 30.4 ng/ml, 30.0 +/- 14.8 ng/ml, 44.8 +/- 21.7 ng/ml, 66.4 +/- 42.8 ng/ml, 8.7 +/- 3.0 ng/ml, and 94.7 +/- 27.9 ng/ml, respectively. All patients except those with RU showed a diminished PGA level. The HP colonization rates of the patients who underwent partial resection were 45.8%, 22.2%, 50%, and 54.2%, respectively (P < 0.05). Age, gender, smoking, the type of gastroenterostomy, and underlying disease did not exert any influence on the measured PGA levels. However, higher PGA levels were observed in HP-colonized patients who either underwent SGPU or had RU. We conclude that various forms of distal gastrectomy, but not RU, elicit an indistinguishable acid secretory ability while HP colonization is responsible for the higher serum PGA levels in some patients following peptic ulcer surgery.

Aged↗

PubMed1998

Sequential variceal pressure measurement by endoscopic needle puncture during maintenance sclerotherapy: the correlation between variceal pressure and variceal rebleeding.

BACKGROUND/AIMS: The risk factors for esophageal variceal rebleeding are little known. Variceal pressure is one of the major determinants of variceal rupture, but the relationship between variceal pressure and variceal rebleeding during maintenance sclerotherapy has not been determined. This study was undertaken to evaluate the relationship between variceal pressure/gradient change and variceal rebleeding during maintenance sclerotherapy. METHODS: Patients with liver cirrhosis and recent esophageal variceal hemorrhage underwent consecutive variceal pressure measurements by direct puncture of the varices before each elective sclerotherapy. RESULTS: In 46 patients, the initial variceal pressure was no different regardless of age, sex, underlying etiology or hepatic reserve. Variceal pressure was higher in large varices, varices with more severe red wale markings, and varices with slower reduction in size during maintenance sclerotherapy. A larger volume of sclerosant was required to eradicate large varices, varices with more severe red wale markings, and varices with slower reduction in size during maintenance sclerotherapy. There was a positive correlation between initial variceal pressure and total amount of sclerosant (r=0.485, p=0.001). Initial variceal pressure was not related to rebleeding. Variceal pressure increased more in patients with rebleeding from varices per se (n=7) than in those without rebleeding (n= 24). There was no difference in pressure change between patients without rebleeding (n=24) and those with rebleeding from variceal ulcers (n=7). CONCLUSIONS: Large varices, severe red color signs and slow reduction in variceal size were associated with higher initial variceal pressure, and more sclerosant was required to eradicate the varices. An increase in variceal pressure during maintenance sclerotherapy indicates a higher risk of variceal rebleeding, but not of variceal ulcer rebleeding.

Aged↗

PubMed1998

Vascular hyporeactivity persists despite increased contractility after long-term administration of isosorbide dinitrate in portal hypertensive rats.

BACKGROUND/AIMS: Portal hypertension is associated with decreased vascular responsiveness to vasoconstrictors, which may contribute to the hyperdynamics. Isosorbide dinitrate is an effective portal hypotensive drug. The present study aimed to investigate whether chronic administration of isosorbide dinitrate could affect vascular responsiveness in portal hypertensive rats. METHODS: Portal hypertension was induced by partial portal vein ligation. Sham-operated (Sham) rats served as controls. There were four animal groups for this study: portal vein ligation-isosorbide dinitrate group, portal vein ligation-vehicle (Veh) group, Sham-isosorbide dinitrate group and Sham-Veh group. Isosorbide dinitrate (5 mg x kg(-1) x 12 h(-1) was given by gavage for 8 days starting 1 day before ligation and continuing thereafter. Mesenteric arteries were removed for contractile study after hemodynamic measurement. RESULTS: Contractile responses to KCI (15-90 mM) and phenylephrine (10(-9)-10(-4) M) were recorded. Both vascular reactivity and sensitivity were significantly reduced in portal vein ligation rats as compared to Sham rats. Chronic isosorbide dinitrate treatment reduced portal venous pressure in portal vein ligation rats. Moreover, the maximal contractile responses to KCl and phenylephrine were significantly enhanced in both portal vein ligation and Sham rats after isosorbide dinitrate treatment, but relative hyporeactivity persisted in portal vein ligation rats. In contrast, a single dose of isosorbide dinitrate did not alter the contractile sensitivity or reactivity to KCl or phenylephrine in either portal vein ligation or Sham rats. CONCLUSION: Our results show that long-term administration of isosorbide dinitrate enhanced vascular contractility in both portal vein ligation and Sham rats, but relative hyporeactivity persisted in portal vein ligation rats.

Administration, Oral↗

PubMed1998

Hemodynamic effects of eight-day octreotide and propranolol administration in portal hypertensive rats.

Octreotide and propranolol are both effective portal hypotensive drugs in the control or prevention of variceal bleeding. The present study was undertaken to investigate the hemodynamic effects of octreotide and propranolol, alone or in combination, in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups: vehicle group (saline, 0.5 ml/day), octreotide group (100 microg/kg/12 hr), propranolol group (30 mg/kg/day), and octreotide (100 microg/kg/12 hr) plus propranolol (30 mg/kg/day) group. Propranolol or saline was administered by gavage, octreotide by subcutaneous injection. Drug was given one day before ligation and continued for eight consecutive days. Systemic as well as splanchnic hemodynamic parameters were measured thereafter. The portal venous pressure, portal tributary blood flow, and cardiac index were significantly reduced by octreotide, propranolol, or octreotide plus propranolol in portal hypertensive rats. Portal territory, systemic, and renal vascular resistances were significantly enhanced, while hepatic arterial blood flow significantly reduced, in the octreotide and octreotide plus propranolol groups as compared to vehicle group. Our results showed that eight-day administration of octreotide, propranolol, or octreotide plus propranolol led to portal hypotensive and antihyperdynamic effects in portal hypertensive rats. Overall, octreotide treatment alone resulted in better antihyperdynamic profiles than propranolol treatment alone. The combination of octreotide and propranolol offered no therapeutic benefits and was slightly less effective than octreotide alone.

Adrenergic beta-Antagonists↗

PubMed1998

Effect of long-term octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis.

1. Both octreotide and isosorbide dinitrate have been shown to have portal hypotensive effects in animals with portal hypertension. Moreover, in both animals and humans with portal hypertension, the reduction of portal pressure was enhanced when nitrovasodilators were combined with propranolol or vasopressin. The present study was undertaken to evaluate the effect of long-term administration of octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis. 2. Portal hypertension was induced by portal vein stenosis. Portal hypertensive rats were allocated into one of four groups (eight rats in each group): vehicle group, octreotide group (100 micrograms/kg via subcutaneous injection every 12 h), isosorbide dinitrate group (5 mg/kg via gastric gavage every 12 h) and combined treatment group. Drug was given for eight consecutive days, starting 1 day before surgery. Haemodynamic values were measured using a radioactive microsphere technique. 3. Long-term octreotide treatment decreased portal pressure and improved the hyperdynamic circulation. In contrast, long-term administration of isosorbide dinitrate reduced portal pressure but did not ameliorate vasodilatation. A combination of octreotide and isosorbide dinitrate improved the hyperdynamic circulation with a reduction of portal pressure. In addition, the mean value of portal pressure after combination treatment was significantly lower than in rats receiving octreotide alone. 4. These results showed that, in rats with portal hypertension, long-term combined administration of octreotide and isosorbide dinitrate improved the hyperdynamic circulation together with a more profound reduction of portal pressure than rats receiving octreotide alone.

Animals↗

PubMed1998

Aminoguanidine ameliorates splanchnic hyposensitivity to glypressin in a haemorrhage-transfused rat model of portal hypertension.

1. Hyposensitivity to vasopressin is a well-documented phenomenon in animals with portal hypertension and patients with cirrhosis subjected to haemorrhage. Excessive formation of nitric oxide is at least partly responsible for the vascular hyporesponsiveness to vasoconstrictors observed in experimental portal hypertension or in rats with haemorrhagic shock. This study investigated whether addition of aminoguanidine, a preferential inducible nitric oxide synthase inhibitor, to glypressin (a long-acting vasopressin analogue) could enhance its portal hypotensive effect in portal-hypertensive rats with bleeding.2. Portal hypertension was induced by partial portal vein ligation. Fourteen days after operation, systemic and portal haemodynamics were measured in stable or bleeding portal vein-ligated rats receiving intravenous glypressin (0.07 mg/kg) or aminoguanidine (70 mg/kg) followed by glypressin infusion. In rats with a hypotensive haemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or aminoguanidine.3. Glypressin resulted in a significantly greater decrease in portal pressure in portal vein-ligated rats without bleeding than in those with bleeding (P<0.001). In contrast, glypressin induced similar changes in mean arterial pressure between the two groups (P>0.05). The addition of aminoguanidine significantly potentiated the portal-hypotensive effect of glypressin in bleeding portal vein-ligated rats (P<0.005) without an effect on the changes in mean arterial pressure induced by glypressin infusion (P>0.05).4. Splanchnic hyposensitivity to glypressin exists in a haemorrhage-transfused rat model of portal hypertension. This hyposensitivity can be ameliorated by the administration of aminoguanidine.

Animals↗