Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We found that measurements of portal blood flow by continuous thermodilution were highly reproducible even after hepatectomy. Our subjects numbered 59 in all: In these patients having diseases of the liver and biliary tract, we studied portal hemodynamics during percutaneous transhepatic portography. Of these, 37 underwent hepatectomy. We chose 19 subjects from this group, and measured again both portal venous flow and portal venous pressure many times, continuing for 14 more days. In all 19 patients checked after hepatectomy, portal hemodynamics became hypodynamic, and this change was greater when the amount of liver resected was large. In 18 of these patients, hemodynamics started to improve after the 7th postoperative day. Changes in hemodynamics were not significantly different in patients with or without cirrhosis. In one patient who died of hepatic failure, the portal hypodynamic state did not improve. With this exception, in patients with major resections, portal venous flow per liver volume had increased after surgery and continued to increase. This was not true for patients with minor resections. Portal hemodynamics are important in the functioning and regeneration of the remaining liver, and it is necessary to understand and medically correct portal hemodynamics before and after hepatectomy.
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PMID:[Measurement of the portal blood flow in man by continuous local thermodilution method: II. Portal hemodynamics before and after hepatectomy]. 301 73

The splanchnic venous system was examined by real-time ultrasonography in 46 patients with cirrhosis and documented portal hypertension and in 32 healthy subjects. Patients with portal hypertension had increased diameter of the splanchnic (portal, splenic, and superior mesenteric) veins (76% of patients), attenuation of the normal inspiratory increase in vein size (59%), and demonstrable portasystemic collateral vessels (umbilical or coronary veins or spontaneous splenorenal shunt) (44%). Splanchnic venous dimensions were significantly increased and changed less with respiration in patients with demonstrable portasystemic collaterals as compared to patients without these vessels. Portal pressure correlated only mildly with portal vein diameter (r = 0.30, p less than 0.05). Ultrasound abnormalities are present in a majority of patients with intrahepatic portal hypertension. However, because increased venous diameter and attenuated change in diameter with respiration are less frequent in patients lacking demonstrable portasystemic collaterals, the sensitivity of the test is least in those patients in whom its specificity is also limited.
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PMID:Utility and limitations of splanchnic venous ultrasonography in diagnosis of portal hypertension. 309 89

We studied contractile properties of portal veins isolated from chronic portal hypertensive rats (PHR) resulting from liver cirrhosis, a model obtained by repeated subcutaneous injections of CCl4 (2 mg/kg) twice weekly for over 45 weeks. Portal venous pressure in vivo was significantly higher in PHR (167.0 +/- 38.7 mmH2O) than in the control normal Wistar rats (NWR) (102.0 +/- 25.5 mmH2O). A pair of portal veins from PHR and NWR were mounted longitudinally in an organ bath and perfused with Tyrode's solution with different K+, Ca2+, and norepinephrine concentrations. The isometric tension was measured by a strain-gauge. Under control conditions, spontaneous phasic contractile force, corrected by cross-sectional area, was greater, and the frequency was lower in PHR than in NWR preparations. The averaged peak contractile force measured at different [K]o (5.4-86.4 mM) was also greater in PHR than in NWR. Force of the tonic contraction measured at different [Ca]o (0.45-5.4 mM), under conditions of 86.4 mM [K]o was significantly larger in PHR than in NWR preparations. However, the Ca2+ sensitivity of both preparations was the same. D-600 (greater than or equal to 0.1 microM) inhibited the tonic contraction in both preparations with an identical sensitivity to the drug. In the presence of norepinephrine (10 microM), the Ca2+ sensitivity of the tonic contraction increased both in PHR and NWR preparations. The increase was more pronounced in PHR and was completely reversed in the presence of the alpha 1-adrenoceptor blocker, prazosin (0.1 microM). The alpha 1-adrenoceptor sensitivity to norepinephrine was not altered in PHR preparations. The rate of Ca2+ release and uptake of intracellular Ca2+ seemed identical in both preparations. Thus, in the absence of norepinephrine, the phasic and tonic contractile forces of portal veins from PHR are larger than that of NWR, probably due to increased membrane Ca2+ permeability. The PHR preparations have a higher affinity for external Ca2+ in the presence of norepinephrine, an additional factor contributing to elevation of portal blood pressure in the presence of chronic liver cirrhosis.
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PMID:Characteristics of contractile response of isolated portal veins from chronic portal hypertensive rats under altered levels of external K+, Ca2+, and norepinephrine concentrations: a comparison with normal Wistar rats. 323 68

Fluoxetine is a specific and potent inhibitor of presynaptic serotonin reuptake and has been shown to be a clinically effective antidepressant. Elimination of the drug depends primarily on hepatic metabolism, with formation of a pharmacologically active demethylated product, norfluoxetine. The present study assesses for the first time the effect of chronic liver disease on these processes. Our data show that in stable alcoholic cirrhosis, the elimination of fluoxetine is significantly reduced. The mean t1/2 was 6.6 vs. 2.2 days and plasma clearance was 4.2 vs. 9.6 ml/min/kg for patients with cirrhosis vs. normal volunteers, respectively. In addition, the formation of norfluoxetine was decreased and its clearance was also reduced. Thus, at steady state both fluoxetine and norfluoxetine concentrations will be higher in patients with cirrhosis, unless the dosage is reduced. Conventional liver tests and indocyanine green clearance in cirrhosis did not correlate in a predictive manner with individual patients' elimination of fluoxetine.
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PMID:Fluoxetine disposition and elimination in cirrhosis. 326 26

During recent 17 years, prophylactic distal splenorenal shunt was carried out on 29 patients. Patients were composed of 18 males and 11 females. Age ranged from 34 to 66 years with an average of 52.4. All patients had risky esophagogastric varices; varices larger than 5 mm in diameter and or varices with red color signs such as cherry red spots endoscopically. Underlying liver disease were cirrhosis of the liver in 27, chronic hepatitis in one, and idiopathic portal hypertension in one. Twenty-three patients were in Child's class A and six were in class B. Thirteen patients underwent the original Warren shunt but the remaining 16 had modified distal splenorenal shunts with expanded polytetrafluoroethylene interposition. Portal-azygos disconnection was routinely performed. One patients (3.4%) died of hepatic failure on the 6th postoperative day. Four patients (14.3%) developed hepatic encephalopathy of mild to moderate degree but no patients have suffered from variceal bleeding until now. The 5-, 10-, and 15-year survival rates were all 85.5 per cent. It is concluded that distal splenorenal shunt is a safe and reliable method to prevent variceal bleeding in a selected group of patients.
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PMID:Prophylactic distal splenorenal shunt for child's class A and B patients at high risk of bleeding. 326 5

To assess the role of intrahepatic portal-systemic shunts in the reduction of portal blood supply to the liver cells in cirrhosis, we measured portal venous flow (blood flow in the portal trunk) by the pulsed Doppler flowmeter and intrahepatic portal-systemic shunt index from the counts over the lungs and liver in both the anterior and posterior projections after instillation of 99mTc-macroaggregated albumin in the portal vein, and calculated portal sinusoidal flow (blood flow into the sinusoids via the portal vein), using the equation, (sequence; see text) in 47 patients with posthepatitic cirrhosis, and measured portal venous flow in 63 healthy adults in whom portal sinusoidal flow should be comparable to portal venous flow. Portal sinusoidal flow was significantly reduced in cirrhotics with an intrahepatic portal-systemic shunt index averaging 24%, whereas portal venous flow was similar in the cirrhotics and control. There was a significant inverse correlation between intrahepatic portal-systemic shunt index and portal sinusoidal flow. When cirrhotics were divided into three stages, based on Child's grading, intrahepatic portal-systemic shunt index was significantly increased in the group order of Child's A (8 +/- 9%), Child's B (27 +/- 22%), and Child's C patients (46 +/- 19%), and portal sinusoidal flow was decreased in the same order. Portal sinusoidal flow was significantly reduced in Child's B and Child's C patients, but not in Child's A patients, compared with the control. In conclusion, intrahepatic portal-systemic shunts may play a role, at least in part, in the reduction of portal blood supply to the liver cells in patients with advanced stage of posthepatitic cirrhosis when large intrahepatic portal-systemic shunts develop.
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PMID:Role of intrahepatic portal-systemic shunts in the reduction of portal blood supply to liver cells in cirrhosis. 338 2

This study was performed to ascertain whether testosterone metabolism is altered in male rats with portal bypass, and whether such changes could contribute to the reduction in serum testosterone concentration and raised serum estrogen levels that are observed in this situation. The metabolic clearance rate of testosterone was determined by a prime-dose constant-infusion technique in male rats subjected to complete portal vein ligation and in sham-operated controls. Testosterone clearance was similar in rats with portal vein ligation and control rats (9.01 +/- 2.29 and 8.26 +/- 2.83 ml/min, respectively) but the clearance per gram of liver was greater in rats with portal vein ligation than in controls (1.18 +/- 0.18 versus 0.68 +/- 0.24 ml/min.g liver, p less than 0.0001). After 180 min of [3H]testosterone infusion, [3H]estradiol comprised 1.2% of plasma total radioactivity in male controls but was increased to 11% in rats with portal vein ligation (p less than 0.005). Similarly, biliary excretion of [3H]estradiol was eightfold greater in male rats with portal vein ligation compared with controls (p less than 0.001). In control male rats, the major metabolites of testosterone present in bile were 2 alpha-hydroxytestosterone, 16 alpha-hydroxytestosterone, and 7 alpha-hydroxytestosterone. Portal bypass was associated with reduced biliary excretion of 2 alpha-hydroxytestosterone and 16 alpha-hydroxytestosterone to approximately 50% of control, but there was no change in the excretion of 7 alpha-hydroxytestosterone. Conversely, portal bypass was associated with increased formation of dihydrotestosterone, indicating stimulated activity of testosterone 5 alpha-reductase. It is concluded that portal bypass in male rats is associated with altered pathways of testosterone metabolism and, in particular, with increased aromatization of testosterone to estradiol. The site of such estradiol formation has not been determined by this in vivo study. However, selective changes occurred in the regiospecific and stereospecific hydroxylation pathways of testosterone and in 5 alpha-reductase activity after portal bypass in male rats. It is concluded that portal bypass, in the absence of parenchymal liver damage, results in demasculinization and feminization of C19 steroid metabolism in the male rat liver. These metabolic changes could be revelant to the pathogenesis of changes in sexual characteristics in cirrhosis.
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PMID:Hepatic testosterone metabolism in male rats with portal bypass. 339 70

Patients maintaining portal perfusion following small-diameter portacaval H grafts have better survival and lower portasystemic encephalopathy rates than those with reversed flow. To determine why this is so, we measured nutrient hepatic blood flow with the use of 99m-Tc-diisopropyl-IDA (DISIDA) clearance pharmacokinetics fractionated into its hepatic arterial and portal venous components. Patients with cirrhosis and portal hypertension had significantly lower nutrient hepatic blood flow than normal persons; this was due almost entirely to reduced portal flow. In patients with prograde portal flow after small-diameter H grafts nutrient hepatic blood flows were nominally reduced from levels seen in patients with portal hypertensive cirrhosis. Postoperative patients with reversed portal flow had significantly less nutrient hepatic blood than those with prograde flow. There was no evidence of significant hepatic arterial compensation for lost portal flow. Of four hemodynamic variables--portal flow direction, portal flow, arterial flow, and nutrient hepatic blood flow--only nutrient hepatic blood flow showed an independent correlation with clinical outcome. Portal perfusion is a critical factor in maintenance of adequate nutrient hepatic blood flow, primarily because hepatic arterial flow does not compensate chronically for lost portal perfusion.
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PMID:Quantitation and fractionation of nutrient hepatic blood flow in normal persons, in persons with portal hypertensive cirrhosis, and after small-diameter portacaval H grafts. 340 65

To assess whether portal venous pressure remains elevated following distal lienorenal shunt surgery, 11 patients with alcoholic cirrhosis were assessed from 0.5 to 59 months following the creation of a distal lienorenal shunt. These were compared with five patients following mesocaval shunt surgery and nine with cirrhosis alone. Portal pressure was measured by direct transhepatic catheterization of the portal vein or by determining intrahepatic pulp pressure. Splenic pulp pressure was also measured in the shunt groups at the time of assessment of shunt patency by scintisplenoportography. All shunts were patent. Four of five patients studied within 10 months of distal lienorenal shunt surgery had persisting portal hypertension (comparable with that in the cirrhosis alone group) and persisting portasplenic gradient. In contrast, five of six patients studied more than 10 months following surgery had portal pressures similar to that following mesocaval shunt surgery and no portasplenic gradient. Thus, with time, selective decompression tends to become total decompression. Whether this correlates with deterioration of hepatic function requires further study.
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PMID:The long-term effect of distal lienorenal shunt surgery on portal venous pressure. 346 41

Propranolol has been reported to reduce portal and wedged hepatic vein pressures in man and may be useful for the prevention of variceal bleeding. However, its mechanism of action remains unclear. We have examined the effect of propranolol on the systemic and hepatic circulations in dogs with chronic bile duct ligation and secondary biliary cirrhosis. Under anesthesia, eight dogs received four increasing doses of propranolol as an i.v. bolus followed by continuous infusion. Systemic and hepatic hemodynamic parameters were measured in basal conditions and after a 30 min infusion for each dose. Portal vein and hepatic artery blood flows were measured with electromagnetic flow meters. All dogs had portal hypertension (portal venous pressure 15.3 +/- 0.8 mm Hg), a hyperdynamic circulation and severe liver disease resulting in a marked decrease of propranolol systemic clearance (8.75 ml per min per kg) and extraction (40%). The first dose of propranolol induced a decrease in heart rate (-27%) and in cardiac index (-21%), and an increase in systemic vascular resistance (+20%). With increasing doses, the systemic vascular resistance decreased with an increase in the cardiac index. Propranolol was not associated with significant modifications of hepatic hemodynamics: portal, wedged and free hepatic venous pressures and hepatic artery blood flow were stable, and portal blood flow decreased slightly at very high propranolol levels. In seven dogs studied without dissection of the hepatic vessels, there was a small decrease in portal pressure, but not in wedged and free hepatic venous pressures with increasing doses of propranolol. Thus, in dogs with intrahepatic portal hypertension, propranolol has significant effects on systemic hemodynamics, but only minimal effects on the hepatic circulation.
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PMID:Effect of propranolol on hepatic and systemic hemodynamics in dogs with chronic bile duct ligation. 348 14


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