丹参桃芎汤对肝纤维化小鼠腹膜淋巴孔的调控与尿钠离子浓度变化的影响

目的寻找治疗肝硬变腹水的有效方药.方法具有腹膜淋巴孔调控作用的丹参配合活血化瘀的桃仁、川芎组成丹参桃芎汤对肝纤维化造模小鼠进行腹膜淋巴孔调控与尿离子浓度变化的实验,并经扫描电镜和计算机图像处理与定量分析.结果预防组、治疗组腹膜淋巴孔孔径、密度与模型组、对照组比较有非常显著性差异(P＜0.001),而尿离子测定,治疗组不及预防组.结论丹参桃芎汤是治疗腹水的有效方剂.     

A novel sodium overload test predicting ascites decompensation in rats with CCl4-induced cirrhosis

BACKGROUND/AIMS: We aimed to develop a non-invasive test to identify the initial alterations of sodium homeostasis and prospectively predict decompensation in preascitic cirrhotic rats. METHODS: The sodium overload test (SOT) was performed in control (CT) and CCl4-induced cirrhotic rats (CH) by calculating the percentage of sodium excreted in the urine after NaCl oral administration (0.5 g/kg). Liver fibrosis was quantified by image cytometry. RESULTS: From the 8th week of CCl4 intoxication, while the daily sodium balance did not change in CH and CT, SOT became significantly lower in the former (62.1+/-13.2 vs 78.8+/-13.2%; P=0.035). At sacrifice, ascites was only present in one animal. The degree of liver fibrosis correlated with SOT. In subsequent experiments, 17 cirrhotic rats developed ascites between the 9th and 14th weeks. SOT remained stable up to 3 weeks before ascites appearance, while it fell significantly to 35+/-19 and 26+/-21% at 2 and 1 week before ascites diagnosis, respectively. Nearly all the rats (95%) with a SOT<60% developed ascites within 3 weeks. CONCLUSIONS: In preascitic cirrhotic rats, SOT unveils sodium metabolism abnormalities earlier than the daily sodium balance and prospectively predicts ascites appearance, identifying rats in a homogeneous stage of cirrhosis, which is essential in pathophysiological studies on sodium retention.     

Structural changes of the diaphragmatic peritoneum in patients with schistosomal hepatic fibrosis: its relation to ascites

The histopathologic changes of the peritoneum of the hemidiaphragm were studied in 30 patients with schistosomal liver disease and compared with ten control subjects. The diaphragmatic peritoneum of patients with ascites was markedly thickened with infiltration of inflammatory cells and collagen bundles resembling the interstitial changes of peripheral lymphedema. Obliteration of diaphragmatic lymphatic stomata with restricted lymph flow as well as excess lymph formation from portal hypertension are both major factors in the magnitude and intractability of ascites associated with schistosomal hepatic fibrosis.     

Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome

Hepatorenal syndrome (HRS) is a functional renal disorder complicating decompensated cirrhosis. Treatments to date, except liver transplantation, have been able to improve but not normalize renal function. The aim of this study was to determine the efficacy of transjugular intrahepatic portosystemic stent shunt (TIPS) as a treatment for type 1 HRS in ascitic cirrhotic patients, following improvement in systemic hemodynamics with a combination of midodrine, octreotide, and albumin (medical treatment). Fourteen ascitic cirrhotic patients with type 1 HRS received medical therapy until their serum creatinine reached below 135 micromol/L for at least 3 days, followed by a TIPS if there were no contraindications. Patients were assessed before and after medical treatment, as well as at 1 week and 1, 3, 6, and 12 months post-TIPS with measurements of renal function, sodium handling, systemic hemodynamics, central blood volume, and hormonal markers. Medical therapy for 14 +/- 3 days improved renal function (serum creatinine: 233 +/- 29 micromol/L vs. 112 +/- 8 micromol/L, P =.001) and renal sodium excretion (5 +/- 2 mmol/d vs. 9 +/- 2 mmol/d, P =.002) in 10 of the 14 patients. TIPS insertion in five of the responders further improved renal function and sodium excretion, so that by 12 months post-TIPS, glomerular filtration rate (96 +/- 20 mL/min, P <.01 vs. pre-TIPS) and urinary sodium excretion (119 +/- 15 mmol/d, P <.01 vs. pre-TIPS) were normal, associated with normalization of plasma renin and aldosterone levels and elimination of ascites. In conclusion, TIPS is an effective treatment for type 1 HRS in suitable patients with cirrhosis and ascites, following the improvement of renal function with combination therapy of midodrine, octreotide, and albumin.     

Increased sympathetic outflow in cirrhosis and ascites: direct evidence from intraneural recordings

OBJECTIVE: To determine if central sympathetic outflow is increased in patients with cirrhosis and ascites. PATIENTS: Eleven patients with cirrhosis and ascites, 8 patients with cirrhosis but without ascites, and 7 age-matched and 8 young healthy volunteers. METHODS: With subjects supine, direct microneurographic recordings of efferent post-ganglionic muscle sympathetic nerve activity were obtained from the peroneal nerve, and sympathetic burst frequency was compared with subjects' blood pressure, heart rate, sodium excretion, catecholamines, and plasma renin activity. All patients with cirrhosis were studied at least 5 days after withdrawal from all medications and after 7 days of a 20 mmol/d sodium, 1-L fluid-restricted diet. Age-matched volunteers were studied after 7 days of 20 mmol/d sodium intake and young healthy volunteers after 7 days of 150 mmol/d sodium intake. RESULTS: Sympathetic nerve activity in ascitic patients (65 +/- 15 bursts/min; mean +/- SD) was markedly increased, whether compared with patients with cirrhosis but without ascites (34 +/- 16 bursts/min; P less than 0.001), age-matched healthy volunteers on similar sodium intake (27 +/- 22 bursts/min; P less than 0.001), or young healthy subjects (21 +/- 10 bursts/min; P less than 0.001). The frequency of muscle sympathetic nerve discharge was directly related to plasma norepinephrine and epinephrine concentrations, plasma renin activity, and heart rate, all of which were increased in those patients with cirrhosis and ascites, and inversely related to 24-hour urinary sodium excretion, the fractional excretion of sodium, and subjects' pulse pressures. Sympathetic nerve activity fell from 78 to 6 bursts/min in one patient after liver transplantation. CONCLUSIONS: This study provides the first direct evidence that elevated plasma norepinephrine concentrations in patients with cirrhosis and ascites are due to increased central sympathetic outflow. Sympathetic nerve activity is not increased in patients with cirrhosis but without ascites. Because there were direct positive correlations of sympathetic nerve activity with plasma norepinephrine concentrations, plasma epinephrine concentrations, plasma renin activity, and heart rate, the increase in central sympathetic outflow in patients with cirrhosis and ascites appears generalized and not restricted to muscle nerves. The anti-natriuretic effects of parallel increases in renal and muscle sympathetic nerve activity could account for the inverse correlation between muscle sympathetic nerve activity and sodium excretion.     

透明质酸钠对兔脓胸胸膜粘连及纤维化的影响

目的探讨透明质酸钠对兔脓胸胸膜粘连及纤维化的影响。方法20只雄性新西兰大白兔随机分为治疗组和对照组，每组10只。在右侧胸膜腔放置导管后，相继注入松节油和金黄色葡萄球菌以诱导脓胸形成，24h时抽取全部胸腔积液，脓胸被证实后，治疗组胸膜腔内注入透明质酸钠3ml（30mg），对照组注入生理盐水3ml。所有动物于24h后肌内注射青霉素20万U／d。96h时再次抽取胸腔积液，检测2次胸腔积液中的白细胞数、中性粒细胞比值、蛋白含量、葡萄糖浓度及pH值。第8天处死兔并开胸观察。结果每组各有9只兔完成实验，治疗组和对照组96h时胸腔积液中自细胞数分别为（25±13）×10^9／L和（37±10）×10^9／L，中性粒细胞比值分别为0．27±0．11和0．50±0．11，蛋白含量分别为（30±4）g／L和（36±4）g／L，治疗组均显著低于对照组，96h胸腔积液中治疗组葡萄糖浓度为（2．4±0．5）mmol／L，显著高于对照组的（3．8±1．3）mmol／L。治疗组和对照组胸膜粘连积分分别为（0．7±0．5）和（3．2±0．7）分，脏层胸膜厚度分别为（28±10）μm和（156±42）μm，成纤维细胞数分别为（37±15）个／mm^2和（163±58）个／mm^2，治疗组均明显少于对照组。结论早期胸膜腔内注入高分子量透明质酸钠可显著减轻兔脓胸胸膜粘连及纤维化，且安全性好。     

Effects of satavaptan, a selective vasopressin V(2) receptor antagonist, on ascites and serum sodium in cirrhosis with hyponatremia: a randomized trial

Hyponatremia in cirrhosis is associated with significant morbidity and mortality and complicates ascites management. Vasopressin receptor antagonists improve serum sodium concentration by increasing renal solute-free water excretion, but their effects on the management of ascites have not been assessed. Our aim was to investigate the effects of satavaptan, a highly selective vasopressin V(2) receptor antagonist, on ascites management and serum sodium in hyponatremic patients with cirrhosis. A total of 110 patients with cirrhosis, ascites, and hyponatremia (serum sodium < or =130 mmol/L) were included in a multicenter, double-blind, randomized, controlled study comparing three fixed doses of satavaptan (5 mg, 12.5 mg, or 25 mg once daily) versus placebo. Duration of treatment was 14 days and all patients received spironolactone at 100 mg/day. Satavaptan treatment was associated with improved control of ascites, as indicated by a reduction in body weight (mean change at Day 14 was +0.49 kg [+/-4.99] for placebo versus +0.15 kg [+/-4.23], -1.59 kg [+/-4.60] and -1.68 kg [+/-4.98] for the 5 mg, 12.5 mg, and 25 mg doses, respectively; P = 0.05 for a dose-effect relationship overall) and a parallel reduction in abdominal girth. This beneficial effect on ascites was associated with improvements in serum sodium (mean change from baseline to day 5 was 1.3 +/- 4.2, 4.5 +/- 3.5, 4.5 +/- 4.8, and 6.6 +/- 4.3 mmol/L for the placebo group and the groups on satavaptan at 5 mg, 12.5 mg, and 25 mg/day, respectively; P < 0.01 for all compared to placebo). Thirst was significantly more common in patients treated with satavaptan compared to those treated with placebo, whereas the frequency of other adverse events was similar among groups. CONCLUSION: The V(2) receptor antagonist satavaptan improves the control of ascites and increases serum sodium in patients with cirrhosis, ascites, and hyponatremia under diuretic treatment.     

Mobilization of malignant ascites with diuretics is dependent on ascitic fluid characteristics.

Serial ascites and plasma volumes were measured during diuresis in nine patients with ascites caused by peritoneal carcinomatosis, four patients with chylous malignant ascites, and three patients with portal hypertension-related ascites caused by massive hepatic metastases. Oral diuretics were given to achieve an adequate natriuresis on a sodium-restricted diet. During the study period (7.8 +/- 3.2 days), patients with peritoneal carcinomatosis and chylous ascites lost 0.49 +/- 0.31 and 0.51 +/- 0.42 kg/day in weight, respectively, with negligible change in ascites volumes (-0.03 +/- 0.11 and 0.02 +/- 0.09 L/day). Patients with ascites caused by massive hepatic metastasis lost 1.06 +/- 0.15 kg/day in weight (P = 0.01 for massive hepatic metastasis vs. peritoneal carcinomatosis) and 0.23 +/- 0.13 L/day of ascites (P less than 0.05 vs. other groups). Plasma volume changes were not significantly different among the three groups. Patients with edema (9/16) had a greater natriuresis and daily weight loss. Three patients with peritoneal carcinomatosis and one with chylous ascites developed renal dysfunction or symptomatic hypotension. No patient with massive hepatic metastasis developed these complications. In patients with ascites caused by peritoneal carcinomatosis or chylous malignant ascites there is no mobilization of ascites, whereas in patients with massive hepatic metastasis, ascites may be mobilized with diuretics.     

Long-term renal sodium handling in patients with cirrhosis treated with transjugular intrahepatic portosystemic shunts for refractory ascites

PURPOSE: The long-term effects of transjugular intrahepatic portosystemic shunts on renal sodium excretion are not known. We sought to determine these long-term effects, as well as to measure the effects of a sodium load in patients who are free of ascites. SUBJECTS AND METHODS: Ten patients with cirrhosis who had been successfully treated with transjugular intrahepatic portosystemic stent shunt for refractory ascites were studied before the shunt and again at 6 and 14 months after the shunt while on a 22 mmol sodium/day diet. At 14 months they were also studied on a 200 mmol sodium/day diet for 7 days without diuretics. Renal sodium handling, central blood volume, neurohumoral factors, and hepatic function were measured. RESULTS: Sodium balance was negative at 6 months (urinary sodium excretion [mean +/- SD] 51 +/- 11 mmol/day versus 7 +/- 2 mmol/day pre-shunt; P < 0.05), was maintained at 14 months (22 +/- 4 mmol/day; P < 0.05 versus pre-shunt), and was associated with normalization of renin activity and aldosterone levels, but not norepinephrine levels, as well as significantly improved renal hemodynamic measurements. Sodium loading with 200 mmol/day resulted in weight gain associated with increased central blood volume and appropriate renal sodium handling in most but not all patients (urinary sodium excretion 188 +/- 14 mmol/day), despite persistent nonsuppressibility of sympathetic hyperactivity. CONCLUSIONS: In cirrhotic patients with refractory ascites treated with a transjugular intrahepatic portosystemic stent shunt, long-term renal sodium handling is improved. Adequate intravascular filling in ascites-free cirrhotic patients with normal portal pressure permits an improved but not normalized renal response to a sodium load, possibly due to persistently elevated sympathetic activity. Therefore, these patients should increase their sodium intake cautiously.     

Nitric oxide and renal functions in liver cirrhosis.

BACKGROUND/AIMS: Nitric oxide, a potent vasodilating agent, has been proposed to play a role in pathogenesis of ascites and hepatorenal syndrome. The aim of this study was to evaluate the interaction between the plasma nitric oxide, nitric oxide synthetase levels and renal functions in patients with different degrees of chronic liver disease. METHODS: The study population included 38 subjects: 14 patients with chronic hepatitis, 11 with preascitic cirrhosis and 13 with ascitic cirrhosis. Nitric oxide and nitric oxide synthetase were determined by colorometric assay. We calculated glomerular filtration rate and fractional sodium excretion. RESULTS: Nitric oxide levels in groups were as follows: 79.28+/-24.86, 99.03+/-21.31, 197.05+/-49.61 microm, respectively. Nitric oxide synthetase levels were 2.64+/-0.56, 3.64+/-0.89, 7.75+/-2.46 micromol/L/sec, respectively. Nitric oxide and nitric oxide synthetase levels in the ascitic cirrhotic group were significantly higher than in the others (p<0.05). When glomerular filtration rates were compared, the only significant difference was determined between the groups with chronic hepatitis and ascitic cirrhosis (92.31+/-25.21, 48.46+/-16.45, p<0.05). Fractional sodium excretion was significantly increased in the ascitic cirrhotic group (4.42+/-2.76, p<0.05). CONCLUSIONS: Nitric oxide and nitric oxide synthetase increased with progression of liver disease, especially in ascitic cirrhosis. We also showed that this increase negatively affects the renal tubular and glomerular functions.     

Total paracentesis in cirrhotic patients with tense ascites and dilutional hyponatremia

OBJECTIVE: The safety of large-volume paracentesis with plasma expander infusion in ascitic cirrhotic patients with advanced liver disease, hyponatremia, or renal failure has not been elucidated. Our aim was to investigate the safety of total paracentesis in cirrhotic patients with ascites and severe hyponatremia. METHODS: Forty-five cirrhotic patients with tense ascites were treated with total paracentesis and infusion of plasma expanders. At inclusion, 20 patients showed severe hyponatremia (serum sodium <130 mEq/L). In the remaining 25 patients, serum sodium was >130 mEq/L (range, 133-146 mEq/L). RESULTS: Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were significantly higher in patients with hyponatremia (PRA: 19.7 +/- 5.8 ng/mL/h; PAC: 217 +/- 35 ng/dL) than in those patients without hyponatremia (PRA: 4.9 +/- 1.1 ng/mL/h; PAC: 95 +/- 31 ng/dL), indicating a more severe systemic hemodynamic deterioration. After paracentesis, PRA and PAC increased similarly in both groups of patients. Serum sodium levels remained unchanged after paracentesis in patients with hyponatremia (127 +/- 0.5 to 128 +/- 1.5 mEq/L) and decreased slightly in patients without hyponatremia (137 +/- 1 to 135 +/- 1 mEq/L; p < 0.005). The incidence of complications during the first hospitalization, the probability of readmission for complications of cirrhosis, and the probability of survival at 1 yr were similar in both groups of patients. CONCLUSIONS: These results indicate that therapeutic paracentesis is a safe treatment for tense ascites in cirrhotic patients with severe hyponatremia.     

Abnormal sympathetic and renal response to sodium restriction in compensated cirrhosis

It has been proposed that in liver cirrhosis portal hypertension causes splanchnic vasodilation and this induces blood volume expansion to maintain blood pressure. The current study was designed to explore the homeostatic response to sodium restriction, a maneuver aiming to contract blood volume, in compensated cirrhosis. Mean blood pressure, sympathetic nervous activity, and proximal sodium reabsorption were evaluated in 16 healthy control and 21 nonazotemic cirrhotic patients (11 without ascites and 10 with ascites) under two experimental conditions: after 4 days on a free sodium diet (basal condition) and after 4 days on a restricted sodium diet (40 mmol/day). No differences were observed in basal conditions in the above parameters between control and cirrhotic patients without ascites. However, cirrhotic patients with ascites showed lower basal values of mean blood pressure and higher basal levels of both plasma norepinephrine and fractional proximal sodium reabsorption than controls. Neither control nor cirrhotic patients with ascites showed significant changes in the measured parameters after sodium restriction. In contrast, in nonascitic patients, this maneuver induced an elevation in plasma norepinephrine concentration (164.4 +/- 24.6 vs. 270.1 +/- 24.9 pg/mL; mean +/- SEM; P less than 0.005) and in fractional proximal sodium reabsorption (86.4 +/- 2.1 vs. 91.8% +/- 0.5%; P less than 0.01). In addition, the nonascitic cirrhotic patients became hypotensive compared with controls (80.9 +/- 1.6 vs. 88.5 +/- 4.8 mm Hg; P less than 0.05) when subjected to the low-sodium diet. In patients without ascites, under conditions of sodium restriction, the decrease in mean arterial pressure correlated inversely with the increase in plasma norepinephrine concentration (r = -0.713; P less than 0.05), whereas the levels of plasma norepinephrine correlated directly with fractional proximal sodium reabsorption (r = 0.893; P less than 0.01). These findings suggest that ineffective circulatory volume is detected in nonascitic cirrhotic patients only under conditions of sodium restriction, but it is always present in cirrhotic patients with ascites, irrespectively of the amount of sodium in the diet. These results are compatible with the existence of fixed arterial vasodilation in cirrhosis.     

Effect of Oxymatrine on the TGFbeta-Smad signaling pathway in rats with CCl4-induced hepatic fibrosis

AIM： To explore the anti-fibrotic effect of Oxymatrine on CCl4-induced liver fibrosis in rats and its modulation on the TGFbeta-Smad signaling pathway. METHODS： One hundred healthy male SD rats were randomly divided into three groups： normal group （n = 20）, treatment group of Oxymatrine （n = 40） and CCh-induced fibrosis group （n = 40）. Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride （CCh soluted in liquid paraffin with the concentration of 300 g/L, the dosage of injection was 3 mL/kg, twice per week for 8 wk）. The treated rats received Oxymatrine via celiac injection at a dosage of 10 mg/kg twice a week at the same time. The deposition of collagen was observed with H＆E and Masson staining. The concentration of serum TGF-β1 was assayed with ELISA. The gene expression of Smads and CBP （CREB binding protein） was detected with in situ hybridization （ISH） and immunohistochemistry （IH）, respectively. All the experimental figures were scanned and analyzed with special figure-analysis software. RESULTS： A significant reduction of collagen deposition and rearrangement of the parenchyma was noted in the liver tissue of Oxymatrine-treated rats. The semi- quantitative histological scores （2.43 ± 0.47 μm^2 vs 3.76 ±0.68, P 〈 0.05） and average area of collagen/in those rats were significantly decreased when compared with hepatic cirrhosis model rats （94.41 ± 37.26 μm^2 vs 290.86 ± 89.37 μm^2, P 〈 0.05）. The gene expression of Smad 3 mRNA was considerably decreased in the treated animals. The A value of Smad 3 mRNA was lower in the treated rats than the model rats （0.034 ± 0.090 vs 0.167 ± 0.092, P 〈 0.05）. Contrarily, the A value of Smad 7 mRNA was increased considerably in the treated animals （0.175 ± 0.065 vs 0.074 vs 0.012, P 〈 0.05）. There was an obvious decrease in the expression of CBP mRNA in treated rats as illuminated by a reduction of its A value when compared with model rats （0.065±0.049 vs 0.235 ?     

Inhibitory effects of saikosaponin-d on CCl4-induced hepatic fibrogenesis in rats

AIM： To investigate the suppressive effect of saikosaponin-d （SSd） on hepatic fibrosis in rats induced by CCh injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB （NF-κB）, tumor necrosis factor-alpha （TNF-α） and interleukins-6 （IL-6）. METHODS： Hepatic fibrosis models were induced by subcutaneous injection of CCh at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses （1.0, 1.5 and 2.0 mg/kg） once daily for 6 wk in combination with CCh, while the control group received olive oil instead of CCh. At the end of the experiment, rats were anesthetized and killed （except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group）. Hernatoxylin and eosin （HE） staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase （ALT）, triglyeride （TG）, albumin （ALB）, globulin （GLB）, hyaluronic acid （HA） and larninin （LN） in serum and the content of hydroxyproline （HYP） in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay （ELISA） and the levels of NF-κBp65 and I-κBa in liver tissue were analyzed by Western blotting. RESULTS： Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-α and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas, the treatment with SScl markedly reduced all the above parameters compared with the model group, especially in the medium gr     

Effects of omapatrilat on cardiac nerve sprouting and structural remodeling in experimental congestive heart failure

BACKGROUND: Congestive heart failure (CHF) results in decreased cardiac sympathetic innervation. OBJECTIVES: The purpose of this study was to test the hypothesis that therapy with the vasopeptidase inhibitor omapatrilat (OMA) attenuates cardiac neuronal remodeling in CHF. METHODS: We induced CHF in dogs with rapid ventricular pacing for 5 weeks with (CHF+OMA group, n = 8) or without (CHF group, n = 10) concomitant OMA treatment (10 mg/kg twice daily). Cardiac catheterization and echocardiography were performed to determine cardiac structure and hemodynamic parameters. Myocardial nerve density was determined by immunocytochemical staining with anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. Seven normal dogs were used as histologic controls. RESULTS: In the CHF group, ascites developed in 3 dogs and 4 dogs died, compared with no ascites or death in the CHF+OMA group (P = .07). In the 6 CHF dogs that survived, all had atrial fibrosis, severely depressed left ventricular systolic function, and increased atrial and ventricular chamber size. OMA treatment decreased the atrial and ventricular chamber sizes and the degree of atrial fibrosis. Most CHF dogs showed severe myocardial denervation, although some showed normal or abnormally high nerve counts. OMA treatment prevented heterogeneous reduction of nerve density. The left ventricular TH-positive nerve densities were 128 +/- 170 microm(2)/mm(2), 261 +/- 185 microm(2)/mm(2), and 503 +/- 328 microm(2)/mm(2) (P < .05), and the atrial GAP43-positive nerve densities were 1,683 +/- 1,365 microm(2)/mm(2), 305 +/- 368 microm(2)/mm(2), and 1,278 +/- 1,479 microm(2)/mm(2) (P < .05) for the control, CHF, and CHF+OMA groups, respectively. CONCLUSION: CHF results in heterogeneous cardiac denervation. Long-term OMA treatment prevented the reduction of nerve density and promoted beneficial cardiac structural remodeling.     

Mechanism of diarrhea in microscopic colitis

AIM: To search the pathophysiological mechanism of diarrhea based on daily stool weights, fecal electrolytes, osmotic gap and pH. METHODS: Seventy-six patients were included: 51 with microscopic colitis (MC) [40 with lymphocytic colitis (LC); 11 with collagenous colitis (CC)]; 7 with MC without diarrhea and 18 as a control group (CG). They collected stool for 3 d. Sodium and potassium concentration were determined by flame photometry and chloride concentration by titration method of Schales. Fecal osmotic gap was calculated from the difference of osmolarity of fecal fluid and double sum of sodium and potassium concentration. RESULTS: Fecal fluid sodium concentration was significantly increased in LC 58.11±5.38 mmol/L (P<0.01) and CC 54.14±8.42 mmol/L (P＜0.05) than in CG 34.28±2.98 mmol/L. Potassium concentration in LC 74.65±5.29 mmol/L (P<0.01) and CC 75.53±8.78 mmol/L (P<0.05) was significantly less compared to CG 92.67±2.99 mmol/L. Chloride concentration in CC 36.07±7.29 mmol/L was significantly higher than in CG 24.11±2.05 mmol/L (P<0.05). Forty-four (86.7%) patients had a secretory diarrhea compared to fecal osmotic gap. Seven (13.3%) patients had osmotic diarrhea. CONCLUSION: Diarrhea in MC mostly belongs to the secretory type. The major pathophysiological mechanism in LC could be explained by a decrease of active sodium absorption. In CC, decreased CI/HCO_3 exchange rate and increased chloride secretion are coexistent pathways.     

Possible causes of central pontine myelinolysis after liver transplantation

AIM: To sum up the clinical characteristics of patients with central pontine myelinolysis (CPM) after orthotopic liver transplantation (OLT) and to document the possible causes of CPM.METHODS: Data of 142 patients undergoing OLT between January 1999 to May 2003 were analyzed retrospectively. Following risk factors during perioperation were analyzed in patients with and without CPM: primary liver disease, preoperative serum sodium level, magnesium level and plasma osmolality, fluctuation degree of serum sodium concentration, and immunosuppressive drug level, etc.RESULTS: A total of 13 (9.2%) neurologic symptoms appeared in 142 patients post-operation including 5 cases (3.5%) with CPM and 8 cases (5.6%) with cerebral hemorrhage or infarct. Two patients developing CPM after OLT had a hyponatremia history before operation (serum sodium<130 mmol/L), their mean serum sodium level was 130.6 +/- 5.54 mmol/L. The serum sodium level was significantly lower in CPM patients than in patients without neurologic complications or with cerebral hemorrhage/infarct (P<0.05). The increase in serum sodiumduring perioperative 48 h after OLT in patients with CPM was significantly greater than that in patients with cerebral hemorrhage/infarct but without neurologic complications (19.5 +/- 6.54 mmol/L, 10.1 +/- 6.43 mmol/L, 4.5 +/- 4.34 mmol/L, respectively, P<0.05). Plasma osmolality was greatly increased postoperation in patients with CPM. Hypomagnesemia was noted in all patients perioperation, but there were no significant differences between groups. The duration of operation on patients with CPM was longer than that on others (492 +/- 190.05 min, P<0.05). Cyclosporin A (CsA) levels were normal in all patients, but there were significant differences between patients with or without neurologic complications (P<0.05). CONCLUSION: CPM may be more prevalent following liver transplantation. Although the diagnosis of CPM after OLT can be made by overall neurologic evaluations including magnetic resonance imaging (MRI) of the head, the mortality is still very high. The occurance of CPM may be associated with such factors as hyponatremia, rapid rise of serum sodium concentration, plasma osmolality increase postoperation, the duration of operation, and high CsA levels.     

Elevated ascitic fluid fibronectin concentration. A non-specific finding

Ascitic fluid fibronectin concentration was measured in 111 specimens by laser nephelometry. Sterile, portal hypertension-related fluid fibronectin concentration (24 +/- 14 micrograms/ml) was significantly lower than the concentration in infected, portal hypertension-related ascites (49 +/- 44 micrograms/ml, P less than 0.001), peritoneal carcinomatosis (123 +/- 45 micrograms/ml, P less than 0.001), massive liver metastases-related ascites (55 +/- 21 micrograms/ml, P less than 0.001), as well as in ascites of other types (94 +/- 42 micrograms/ml, P less than 0.001). The percentage of samples with fibronectin concentration, greater than 75 micrograms/ml, was 0% for sterile, portal hypertension-related ascites, 28% for infected, portal hypertension-related ascites, 89% for peritoneal carcinomatosis, 20% for massive liver metastases-related ascites, and 72% for ascites of other types. Ascitic fluid fibronectin concentration correlated in a linear fashion with ascitic fluid total protein (r = 0.81, P less than 0.001). Fibronectin concentration in ascites appears to be elevated under a variety of conditions and does not appear to be a specific marker for cancer.     

Systemic Availability of Propionate and Acetate in Liver Cirrhosis

In 15 patients with cirrhosis of the liver and 10 control subjects, 7.5 mmol sodium propionate and 7.5 mmol sodium acetate were instilled endoscopically into the duodenum. Venous concentrations of propionate and acetate were measured for 90 min after administration of the enteral dose by gas-liquid chromatography. In patients with liver cirrhosis, propionate rose from a basal value of 6.1 +/- 4.7 (SD) microM to a peak concentration of 50.1 +/- 25.6 microM, whereas, in controls, it rose only from 1.4 +/- 1.6 to 10.3 +/- 7.6 microM. The oral propionate clearance was significantly lower in patients with cirrhosis (4.51 +/- 1.63 L/min) than in controls (118.47 +/- 154.79 L/min). Acetate went up from 39.5 +/- 16.3 to 134.1 +/- 62.7 microM in patients with cirrhosis and from 60.9 +/- 19.0 to 102.0 +/- 44.0 microM in controls. The oral acetate clearance was lower in patients with liver cirrhosis (2.80 +/- 2.17 L/min) than in control persons (10.86 +2- 5.72 L/min). The differences between the groups were more striking for propionate than for acetate values. It is concluded that the systemic availability of propionate and acetate is higher in patients with liver cirrhosis than in controls. This may be due to portosystemic shunting and/or diminished hepatic and extrahepatic extraction of the acids.