肝硬化患者血浆内皮素和一氧化氮水平及与肾功能状态的关系

测定不同阶段肝硬化患者血浆的NO、ET水平，探索它们对肝硬化腹水形成和肾功能损害所起的作用及其相互关系。测血浆NO的代谢产物NO2^-浓度（Griess法），ET-1浓度（放免法）及肾功能。1.血浆NO浓度在肝硬化各组均明显高于正常对照组，在肾衰组明显高于有腹水、无肾衰组。血浆ET浓度在肝硬化各组均明显高于正常对照组，肾衰组明显高于有腹水、无肾衰组。2.肝硬化患者血浆ET浓度与血肌酐呈正相关，与肌酐清除率、血钠、尿钠呈负相关。3.肝硬化患者血浆NO与ET水平呈正相关。血浆NO和ET升高可能在肝硬化病程进展中起了重要作用，是形成腹水和引起肾功损害的重要因素，二者相互依赖、相互影响的协同作用是肝硬化进展及出现并发症的重要机制之一。     

Plasma endothelin levels in cirrhotic subjects.

Endothelin-1, a potent vasoconstrictor peptide with 21 amino acid residues, is released by the vascular endothelium. Plasma immunoreactive endothelin levels were measured in 23 patients with cirrhosis and in 20 healthy subjects. Concentrations were significantly lower in patients with non-uraemic cirrhosis than in normal subjects (19.4 +/- 8.9 pmol/l vs. 48.8 +/- 24.8 pmol/l, p less than 0.002). Plasma renin, aldosterone, atrial natriuretic peptide, arginine-vasopressin and catecholamines did not show significant correlations with plasma endothelin-1 levels. Furthermore, there were no significant differences in plasma endothelin levels for etiology of cirrhosis, presence of ascites or varices. These data suggest that low circulating endothelin may be involved in the development or maintenance of systemic vasodilatation in cirrhosis.     

Hyperglucagonaemia in cirrhotic patients and its relationship to the severity of cirrhosis and haemodynamic values

Plasma glucagon concentrations were measured in 160 cirrhotic patients (Pugh's grade A in 52 patients, Pugh's grade B in 64 patients and Pugh's grade C in 44 patients). These values were compared with plasma glucagon concentrations in 57 age and sex-matched healthy subjects. Systemic and portal haemodynamic measurements, effective renal plasma flow and creatinine clearance were recorded for each patient. Plasma glucagon levels were significantly increased in cirrhotic patients compared with healthy subjects. In addition, plasma glucagon levels were higher in cirrhotic patients with ascites than in those without ascites and were increased in relation to the severity of cirrhosis as assessed by Pugh's score. Multiple linear regression found that only Child-Pugh's score was estimated to be an independent predictor of hyperglucagonaemia in cirrhotic patients. However, in patients with different degrees of oesophageal varices and in patients without oesophageal varices, plasma glucagon concentrations were no different among the different groups of patients, but were still higher than plasma glucagon concentrations in healthy subjects. In contrast, plasma glucagon levels were negatively correlated with mean arterial pressure and systemic vascular resistance. The results of the present study suggest that impairment of liver function plays, in part, a role in increased plasma glucagon levels observed in patients with cirrhosis. In addition, these data support the hypothesis that hyperglucagonaemia may contribute, at least in part, to the pathogenesis of peripheral arterial vasodilatation in cirrhosis with portal hypertension.     

Dendroaspis natriuretic peptide in hepatic cirrhosis

OBJECTIVES: Dendroaspis natriuretic peptide (DNP) is a novel peptide that is structurally similar to atrial, brain, and C-type natriuretic peptides. Many natriuretic peptides are increased in hepatic cirrhosis, but the role of DNP in cirrhosis is unknown at present. The aim of the study was to investigate plasma levels of dendroaspis natriuretic-like immunoreactivity in cirrhosis. METHODS: We measured plasma concentrations of DNP by radioimmunoassay methods in 12 cirrhotic patients without ascites and 44 cirrhotic patients with ascites, and compared these values with 20 age-matched healthy subjects. Renal function, plasma cGMP concentration, plasma renin activity, and plasma endothelin concentration were measured in each patient. RESULTS: Patients without ascites had circulating levels of DNP similar to those of healthy subjects. By contrast, patients with ascites had increased circulating DNP levels compared to both patients without ascites and healthy subjects. In addition, circulating levels of DNP increased in relation to the severity of cirrhosis. Significant positive correlations were also found between DNP levels, endothelin concentrations, and plasma renin activity. CONCLUSIONS: The results of this study indicate that plasma DNP is increased in cirrhotic patients with ascites.     

Plasma erythropoietin level in patients with cirrhosis and its relationship to the severity of cirrhosis and renal function

BACKGROUND AND AIM: The level of plasma erythropoietin (EPO) in patients with cirrhosis is controversial. It is known that overproduction of nitric oxide (NO) plays, in part, a role for the development of peripheral arterial vasodilatation in cirrhosis with portal hypertension. It has also been hypothesized that a possible interaction is noted between endogenous EPO and NO production. The current study was undertaken to evaluate the relationship between plasma EPO levels and the severity of liver disease, hemodynamic values, renal functions, and plasma nitrate/nitrite levels in patients with cirrhosis. METHODS: The authors measured the biochemistry, plasma EPO and nitrate/nitrite levels in 67 patients with cirrhosis (Child-Pugh class A in 23 and Child-Pugh class B and C in 44) and compared their values with those in 34 healthy subjects. Systemic and splanchnic hemodynamic measurements and effective renal plasma flow were obtained from cirrhotic patients. RESULTS: Plasma EPO and nitrate/nitrite levels were significantly increased in patients with cirrhosis compared with healthy subjects. Additionally, plasma EPO values were higher in cirrhotic patients with ascites or with anemia than in those without ascites or without anemia, respectively. Plasma EPO levels were positively correlated to the hepatic venous pressure gradient (HVPG) and Child-Pugh score, negatively correlated to the renal and hepatic blood flows, but were not correlated to nitrate/nitrite level and systemic vascular resistance in cirrhotic patients. Multiple regression analysis showed that HVPG and renal plasma flow were independent predictors for the elevated EPO level in cirrhotic patients. CONCLUSIONS: Plasma EPO levels were increased in patients with cirrhosis compared with those in healthy subjects. The increase in plasma EPO levels is related to the degree of portal hypertension, the severity of cirrhosis and the renal plasma flow. In contrast, the EPO levels had no correlation to the nitrate/nitrite levels and systemic vascular resistance in patients with cirrhosis.     

Increased urinary endothelin excretion in patients with liver cirrhosis

The urinary endothelin level in patients with chronic liver disease was determined in order to explore its possible involvement in renal function. The plasma endothelin level was significantly higher in patients with liver cirrhosis (LC) than in those with chronic hepatitis (CH) or in control patients (C). Similarly, urinary endothelin excretion in LC was significantly increased, compared with CH and C. Urinary endothelin demonstrated a significant positive correlation with creatinine clearance. The ratio of endothelin clearance/creatinine clearance did not differ statistically among the three groups. Urinary sodium excretion in LC was positively correlated with plasma endothelin, but not with urinary endothelin. Urinary endothelin excretion demonstrated a significant negative correlation with urinary kallikrein in LC. The present data suggest that increased urinary endothelin excretion in cirrhotic patients primarily depends upon elevated plasma levels of endothelin, but not renal production. Also, a possible link between endothelin and the kallikrein-kinin system in liver cirrhosis is indicated.     

Clinical significance of elevated plasma endothelin concentration in patients with cirrhosis.

Endothelin is a newly discovered potent vasoconstrictor peptide. To explain the clinical significance of endothelin in patients with chronic liver diseases, we measured the plasma concentration of endothelin in patients with chronic hepatitis (n = 15), cirrhosis with ascites (n = 8) and cirrhosis without ascites (n = 12), and we compared the findings with the plasma concentration of endothelin in normal controls (n = 14). The plasma endothelin concentration was significantly higher in patients with cirrhosis with ascites than in normal controls (8.3 +/- 2.3 pg/ml vs. 3.3 +/- 1.4 pg/ml, mean +/- S.D., p less than 0.001), whereas no significant difference was observed between normal controls and the other groups of patients (cirrhosis without ascites = 5.0 +/- 1.3 pg/ml; chronic hepatitis = 3.8 +/- 1.2 pg/ml). In patients with cirrhosis, the plasma endothelin concentration showed a significant negative correlation with creatinine clearance (r = -0.73, p less than 0.01), but no significant correlation was observed between plasma endothelin concentration and fractional excretion of filtered sodium. Furthermore, plasma endothelin levels were significantly higher in patients with endotoxemia than in those without (10.1 +/- 2.1 pg/ml vs. 4.9 +/- 1.2 pg/ml, p less than 0.001). From these results, elevated plasma endothelin, which has a close relation to endotoxemia, may play a contributory role in kidney dysfunction in patients with cirrhosis.     

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.     

Plasma immunoreactive endothelin in essential hypertension

PURPOSE: Endothelin plays a role in the regulation of vascular tonus. Therefore, it has been hypothesized that increased production or release of endothelin or both may contribute to the pathogenesis of hypertension. To assess any changes in the plasma endothelin concentration in essential hypertension, plasma immunoreactive endothelin concentrations were measured in patients with essential hypertension. PATIENTS AND METHODS: We measured plasma immunoreactive endothelin concentrations in 42 subjects with essential hypertension, 12 subjects with borderline hypertension, and 25 normotensive control subjects. RESULTS: The concentrations were higher in hypertensive patients than in borderline hypertensive patients and normotensive subjects (both p less than 0.05), although values in normotensives and hypertensives overlapped. Reverse-phase high-performance liquid chromatography (HPLC) and radioimmuno-assay showed two components of plasma endothelin, one corresponding to synthetic endothelin-1 (1-21) and the other corresponding to synthetic big endothelin (human, 1-38). The HPLC profile of plasma endothelin of hypertensive patients was the same as that of normotensive subjects. Hypertensives with reduced glomerular filtration rates or increased serum creatinine levels had higher plasma endothelin concentrations than hypertensive patients as a whole (p less than 0.05). Mean blood pressure and serum creatinine levels were correlated to plasma endothelin in the hypertensives. Correlation was negative between glomerular filtration rate and the endothelin level in the hypertensives. CONCLUSION: Plasma endothelin was elevated in many hypertensive patients with severe hypertension or renal involvement. Its major components were endothelin-1 and big endothelin.     

Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure

BACKGROUND/AIMS: C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is considered to be involved in the regulation of vascular tone. Furthermore, the recent demonstration of CNP in human kidney and urine may indicate a role for CNP in fluid and electrolyte homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver. METHODS: Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate renal extraction ratios of CNP. A sensitive and specific radioimmunoassay was applied after solid phase extraction of samples. RESULTS: Plasma CNP was lower in cirrhotic patients with normal and impaired renal function than in controls (3.0 (0.4) and 2.7 (0.2) v. 4.2 (0.4) pg/ml, respectively; p<0.05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) v. 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; p<0.05). Urinary CNP was found to be inversely related to urinary sodium excretion in cirrhotic patients (r=-0.56; p<0.01). No differences were observed between arterial and renal venous concentrations of CNP in cirrhosis (2.4 (0.2) v. 2.4 (0.2) pg/ml). In cirrhotic patients with hepatorenal syndrome or refractory ascites (n=5), urinary CNP decreased from 132 (59) to 38 (7) ng/g creatinine (p<0.05) one week after either ornipressin infusion or insertion of a transjugular intrahepatic portosystemic shunt together with an increase in urinary sodium excretion from 27 (17) to 90 (34) mmol/24 hours. CONCLUSIONS: Increased urinary CNP in cirrhotic patients in the absence of renal arteriovenous concentration gradients suggests enhanced renal CNP production in cirrhosis. Furthermore, an inverse relation between urinary CNP and urinary sodium excretion suggests a role for this peptide in renal sodium handling in patients with cirrhosis.     

One-week losartan administration increases sodium excretion in cirrhotic patients with and without ascites

Background. Losartan, a highly selective angiotensin II type 1 receptor antagonist, has been reported to have a significant portal hypotensive effect in cirrhotic patients. A recent study also showed that losartan exerted a dramatic natriuretic effect in preascitic cirrhosis. The influence of losartan on renal hemodynamics and sodium homeostasis in cirrhotic patients with ascites is unclear. This study was undertaken to evaluate the renal effects of 1-week losartan treatment in cirrhotic patients with and without ascites. Methods. All 12 patients in the study received a daily oral dose of 25 mg losartan for 7 consecutive days. Effective renal plasma flow, urine volume, creatinine clearance, 24h urine sodium excretion and fractional excretion of sodium, blood urea nitrogen, and serum creatinine were measured before and after treatment. Results. In cirrhotic patients without ascites, creatinine clearance, 24-h urinary sodium excretion, and fractional excretion of sodium were significantly increased after losartan administration. Effective renal plasma flow and serum creatinine showed almost no change after treatment. In cirrhotic patients with ascites, creatinine clearance, 24-h urinary sodium excretion, fractional excretion of sodium, and effective renal plasma flow were significantly increased after losartan administration. In addition, the magnitudes of the increases in the fractional excretion of sodium and in the 24-h urinary sodium excretion were greater in cirrhotic patients with ascites than in those without ascites. Conclusions. One-week treatment with losartan increases sodium excretion in association with an improvement of renal function in cirrhotic patients with and without ascites. The natriuretic effect was more profound in cirrhotic patients with ascites than in those without ascites. Received: May 1, 2001 / Accepted: August 24, 2001     

Systemic nitric oxide production and renal function in nonazotemic human cirrhosis: a reappraisal

OBJECTIVES: Several studies in human cirrhosis have demonstrated increased nitric oxide (NO) production. In experimental animals, intracerebroventricular administration of NO donors causes a marked depression of the endogenous dopaminergic activity, a function known to be physiologically recruited and exerting a natriuretic function in patients with compensated cirrhosis. The aim of this study is to evaluate the interaction between the systemic plasma levels of NO, the endogenous dopaminergic activity and the main parameters of renal function in patients with liver cirrhosis of differing degrees of severity. METHODS: A total of 21 patients (11 with preascitic and 10 with nonazotemic diuretic-free ascitic cirrhosis) and 10 healthy control subjects underwent the following tests: a) basal plasma renin activity (PRA) and aldosterone levels; b) renal clearances of sodium, potassium, inulin, para-minohippurate and lithium (the latter being a measure of the fluid delivery to the distal nephron); c) NO systemic plasma levels measured through paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes; d) endogenous dopaminergic activity, evaluated by means of the incremental prolactin and aldosterone plasma levels after dopaminergic blockade with i.v. metoclopramide. RESULTS: NO plasma values and endogenous dopaminergic activity, although significantly increased with respect to healthy controls, were not different in the two groups of patients. The plasma NO/PRA ratio was significantly higher in the group of compensated patients with respect to ascitic cirrhotics (respectively, 18.3 +/- 11.8 vs 3.5 +/- 2.6 A.U./ng/ml/h, p < 0.001). Compared with compensated cirrhotics, patients with ascites showed significantly lower values of glomerular filtration rate (GFR) and renal plasma flow (RPF). Interestingly, GFR values were substantially the same in the ascitic patients and the control subjects. Compensated patients displayed a significant positive correlation between metoclopramide-induced incremental aldosterone plasma levels (i.e., endogenous dopaminergic tone) and fractional excretion of sodium (r = 0.58; p < 0.05). In the group of compensated patients, NO levels correlated inversely with creatinine plasma concentrations (r = -0.85; p < 0.001) and directly with inulin clearance (r = 0.65; p < 0.05). CONCLUSIONS: These data show that, at least in compensated cirrhotic patients, the stimulation of systemic NO production and the increased dopaminergic function may be mechanisms preventing renal perfusion, GFR, and fractional excretion of sodium from precocious reductions.     

肝硬化患者血浆洋地黄样免疫反应物质水平的临床研究

目的 洋地黄样免疫反应物质(DLIS)是参与机体水钠代谢调控的体液因子之一。本文研究肝硬化患者血浆DLIS水平的改变及规律性,并探讨其发生机理。 方法 以地高辛抗体经放射免疫法(RIA)检测80例肝硬化患者的血浆DLIS水平,对照组为50名正常人。 结果 肝硬化组血浆DLIS水平显著高于对照组,其中腹水组又显著高于无腹水组,大量腹水组则显著高于中少量腹水组,Child A,B,C各组间亦存在显著性差异。肝硬化组血浆DLIS水平与肝肾功能障碍及水钠代谢失衡的实验室指标呈显著相关性。 结论 研究结果表明,血浆DLIS水平的改变与肝硬化的病理生理过程有密切关系,即肝硬化时的机体水钠超负荷状态及肝肾功能障碍可能导致DLIS的分泌、代谢及清除的异常或失调。     

Circulating endogenous cannabinoid anandamide and portal, systemic and renal hemodynamics in cirrhosis.

BACKGROUND: Endocannabinoids may participate in the homeostasis of arterial pressure. Recently, anandamide, the most extensively studied endocannabinoid, has been proposed as a key mediator in the peripheral arterial vasodilation of cirrhosis. OBJECTIVES: To determine if circulating levels of anandamide are related to the extent of the peripheral arterial vasodilation, the severity of portal hypertension and the degree of liver and renal dysfunction of patients with cirrhosis. METHODS: Plasma levels of anandamide and several systemic, portal and renal hemodynamic parameters were determined in 18 patients with cirrhosis and eight healthy subjects (control group). RESULTS: Plasma levels of anandamide were elevated in patients compared to the control group (P<0.05), nevertheless, no differences between patients with ascites and well-compensated patients were found. There was no correlation between anandamide concentration and arterial pressure, cardiac output and systemic vascular resistance, Child-Pugh's score, portal pressure, renal vascular resistance, plasma renin activity or plasma aldosterone concentration. CONCLUSIONS: Circulating levels of anandamide are increased in cirrhotic patients. However, this elevation was unrelated to the extent of arterial vasodilation, the severity of portal hypertension or the degree of hepatic and renal dysfunction. Although a local hormonal action cannot be excluded, our results do not support a relevant contribution of this system in the hemodynamic disturbance of cirrhosis.     

Plasma levels of brain natriuretic peptide in patients with cirrhosis.

Plasma levels of brain natriuretic peptide, a recently identified cardiac hormone with natriuretic activity, were measured in 11 healthy subjects, 13 cirrhotic patients without ascites, 18 nonazotemic cirrhotic patients with ascites and 6 patients with cirrhosis, ascites and functional kidney failure. Plasma levels of brain natriuretic peptide were similar in healthy subjects and cirrhotic patients without ascites (5.56 +/- 0.65 and 7.66 +/- 0.68 fmol/ml, respectively). In contrast, cirrhotic patients with ascites, with and without functional kidney failure, had significantly higher plasma concentrations of brain natriuretic peptide (19.56 +/- 1.37 and 16.00 +/- 1.91 fmol/ml, respectively) than did healthy subjects and patients without ascites (p less than 0.01); no significant difference was found between the two groups of cirrhotic patients with ascites with respect to this parameter. In the whole group of cirrhotic patients included in the study, brain natriuretic peptide level was directly correlated with the degree of impairment of liver and kidney function, plasma renin activity and plasma levels of aldosterone and atrial natriuretic peptide. The results of this study indicate that brain natriuretic peptide is increased in cirrhotic patients with ascites and suggest that sodium retention in cirrhosis is not due to deficiency of this novel cardiac hormone.     

肝硬化患者血浆降钙素基因相关肽及内皮素-1水平的变化

目的 探讨肝硬化患者血浆降钙素基因相关肽（ＣＧＲＰ）及内皮素－１（ＥＴ－１）水平的变化,了解此二者之间及它们与肝硬化门脉高压形成及局长和肝功能损伤的关系。方法 用放免法检测２４例正常人和６１例肝硬化患者血浆ＣＧＲＰ和ＥＴ－１水平。结果 肝硬化组血浆ＣＧＲＰ及ＥＴ－１水平显著高于对照组,且在肝功能分级中,呈现ＣｈｉｌｄＣ〉Ｃｈｉｌｄ Ｂ〉ＣｈｉｌｄＡ的规律。组间分析表明肝硬化患者食管静脉曲张伴大中量     

Ascites Fluid and Plasma Calprotectin Concentrations in Liver Disease

Background: Calprotectin, a marker of neutrophil activation, has been associated with a poor prognosis in alcohol-induced cirrhosis. The aims were to study concentrations of calprotectin in patients with various liver diseases, and to further investigate the prognostic value of calprotectin in cirrhosis. Methods: Plasma calprotectin concentrations were determined in 84 patients with alcohol-induced liver disease, 32 hepatitis B or C infected patients, 33 patients with liver disease of other aetiologies, 7 patients with combined aetiologies and in 24 patients with malignant disease. Thirty healthy individuals were included as controls. Ascites calprotectin concentrations were determined in patients with ascites (n = 75). Follow-up for survival was performed after a median observation period of 10 months. Results: Increased plasma and ascites calprotectin concentrations were observed in malignant disease compared to non-malignant disease (P < 0.0001). Plasma calprotectin concentrations were low in viral liver disease compared to patients with non-viral liver disease (P = 0.02) and to controls (P = 0.0002). Plasma calprotectin (>median) was a highly significant marker of poor survival in alcohol-induced cirrhosis (P = 0.001), but was of no prognostic value in non-alcohol-induced cirrhosis (P = 0.88). In decompensated cirrhosis high (>upper quartile) ascites calprotectin concentrations were associated with an increased mortality (P = 0.002), as were high (>median) plasma calprotectin levels (P = 0.009). Conclusion: The prognostic importance of calprotectin in alcohol-induced cirrhosis is confirmed and demonstrated as specific for alcohol-induced liver disease. Low calprotectin levels are indicated in viral liver disease, and an association between high ascites calprotectin levels and malignant ascites was observed.     

Relationships between the severity of cirrhosis and haemodynamic values in patients with cirrhosis

Abstract The relationship between the severity of cirrhosis and systemic and hepatic haemodynamic values was evaluated in 193 patients with cirrhosis, most of whom were diagnosed with post-necrotic cirrhosis. It was found that the hepatic venous pressure gradient and cardiac output in Pugh's A patients (13.6 ± 4.8 mmHg and 6.2 ± 1.6 L/min, mean ± s.d.) were significantly lower than in both Pugh's B (16.8 ± 4.3 mmHg and 7.3 ± 2.1 L/min) and Pugh's C (18.8 ± 5.5 mmHg and 7.4 ± 2.3 L/min) patients ( P < 0.01), respectively. In contrast, the systemic vascular resistance in Pugh's A patients (1232 ± 369 dyn/s per cm⁵) was significantly higher than in both Pugh's B (1016 ± 345 dyn/s per cm⁵) and Pugh's C (935 ± 234 dyn/s per cm⁵) patients ( P < 0.01), respectively. Additionally, not only was there a positive correlation found between Pugh's score and cardiac output and hepatic venous pressure gradient, but a negative correlation was found between Pugh's score and systemic vascular resistance. It was also confirmed that the degree of portal hypertension and the hyperdynamic circulation were more severe in patients with ascites than in those without ascites. However, there were no statistically significant differences in hepatic venous pressure gradient among patients with F1, F2 and F3 esophageal varices (15.7 ± 4.0, 17.0 ± 4.8 and 18.0 ± 4.8 mmHg, respectively). It is concluded that in those patients with cirrhosis, the severity of cirrhosis is closely related to the degree of the hyperkinetic circulatory state and portal hypertension.     

Elevated plasma endothelin in patients with diabetes mellitus

Summary Plasma concentrations of endothelin, a vasoconstrictor peptide released from vascular endothelial cells, have been measured by radioimmunoassay in 100 patients with diabetes mellitus and 19 healthy subjects. The plasma immunoreactive-endothelin concentrations were found to be greatly raised in the patients with diabetes (1,880±120 fmol/l, mean±SEM) compared with the healthy subjects (540±50 fmol/l, p<0.005). The elevation of immunoreactive-endothelin could not be explained by secondary changes in blood pressure or renal disease and did not correlate with the presence of diabetic retinopathy, duration of diabetes mellitus, fasting blood glucose or serum fructosamine. Fast protein liquid chromatographic analysis of the diabetic plasma immunoreactive-endothelin showed three forms, one in a very big molecular weight position, one intermediate and one in the position of endothelin-1 itself. No material appeared in the positions of endothelin-2 and 3. Chromatographic analysis of normal plasma showed only the big molecular weight peak while material in the endothelin-1,2 or 3 positions was below detection. The elevation of endothelin in diabetic patients may be a marker of, and further exacerbate, their vascular disease.     

Plasma human atrial natriuretic factor in cirrhosis and ascites with and without functional renal failure

Functional renal failure of cirrhosis (FRFC) is a usually fatal syndrome of acute renal failure occurring in patients with advanced liver disease. Although not conclusively proven, most evidence suggests that renal arterial and arteriolar vasoconstriction is the cause of the renal failure in these patients. However, the mediators of the vasoconstriction remain unknown. Human atrial natriuretic factor (hANF) is a hormone with potent natriuretic, diuretic, and vasorelaxant properties. A deficiency of hANF could lead to renal arterial vasoconstriction and avid renal sodium retention as seen in FRFC. This study was undertaken to determine if patients with FRFC are deficient in circulating hANF. Seven patients with advanced alcoholic liver disease and renal failure of unknown cause (FRFC) were compared with 7 patients with advanced alcoholic liver disease, ascites, and normal serum creatinine as well as with 14 healthy volunteers. Plasma hANF was measured by radioimmunoassay. Plasma hANF was 742 +/- 227 pg/ml (mean +/- SEM) in patients with FRFC compared with 360 +/- 70 pg/ml in patients with liver disease and normal serum creatinine (p greater than 0.05) and 28 +/- 5.7 pg/ml in healthy volunteers (p less than 0.005 vs. FRFC and chronic liver disease, ascites, and normal serum creatinine). Thus, FRFC is not caused by a deficiency of circulating hANF. The elevated plasma hANF levels in patients with chronic liver disease and continued sodium retention may suggest a renal insensitivity to the natriuretic effects of hANF.