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.     

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.     

Atrial natriuretic factor and renin-aldosterone in volume regulation of patients with cirrhosis

The role of the atrial natriuretic factor and of the main counteracting sodium-retaining principle, the renin-aldosterone system, in acute volume regulation of cirrhosis of the liver has been investigated. Central volume stimulation was achieved in 21 patients with cirrhosis, 11 without and 10 with ascites, and 25 healthy controls by 1-hr head-out water immersion. Immersion prompted a highly significant (p less than 0.001) increase of atrial natriuretic factor plasma concentrations in cirrhotic patients without ascites from 8.5 +/- 1.3 fmoles per ml to 16.5 +/- 2.6 fmoles per ml, comparable to the stimulation in control subjects (6.0 +/- 0.6 fmoles per ml to 13.6 +/- 2.6 fmoles per ml). In cirrhotic patients with ascites, atrial natriuretic factor increase (from 7.7 +/- 1.3 fmoles per ml to 11.4 +/- 2.3 fmoles per ml) was blunted (p less than 0.05). Plasma renin activity and plasma aldosterone concentration were elevated in cirrhotic patients, especially in the presence of ascites. Following immersion, plasma renin activity and plasma aldosterone concentration were reduced similarly in all groups. Water immersion induced a more pronounced natriuresis and diuresis in control subjects than in cirrhotic patients. Neither atrial natriuretic factor nor plasma renin activity nor plasma aldosterone concentration alone correlated to sodium excretion. However, atrial natriuretic factor to plasma aldosterone concentration ratios were closely correlated to basal and stimulated natriuresis in cirrhotic patients, particularly in those with ascites. These data suggest that atrial natriuretic factor and the renin-aldosterone system influence volume regulation in patients with cirrhosis.     

Plasma endothelin levels in patients with cirrhosis and their relationships to the severity of cirrhosis and renal function

Background/Aims: Increased plasma endothelin levels have been reported in patients with cirrhosis. However, the relationship between plasma endothelin concentrations and hyperdynamic circulation or renal functions has not been documented.Methods: We measured the plasma endothelin-1 and endothelin-3 concentrations using radioimmunoassay in 96 patients with cirrhosis (Pugh's A in 26, Pugh's B in 45 and Pugh's C in 25) and compared these values to 56 age- and sex-matched healthy subjects. Systemic and portal hemodynamic measurements, effective renal plasma flow, creatinine clearance, plasma aldosterone concentration and plasma renin activity were recorded for each patient.Results: Plasma endothelin-1 and endothelin-3 levels were significantly increased in patients with cirrhosis compared to healthy subjects. Additionally, plasma endothelin-1 and endothelin-3 values were higher in patients with cirrhosis and ascites than in those without ascites. Moreover, plasma endothelin-1 levels increased in relation to the severity of cirrhosis. On the other hand, modest negative correlations were found betwen endothelin-1 and creatinine clearance or effective renal plasma flow.Conclusions: Plasma endothelin-1 and endothelin-3 levels are increased in patients with cirrhosis compared to healthy subjects. The increase in plasma endothelin-1 levels is related at least in part to the severity of cirrhosis. Increased endothelin-1 levels may possibly contribute to renal dysfunction in patients with cirrhosis.     

Atrial natriuretic factor in cirrhotic patients with tense ascites. Effect of large-volume paracentesis

The plasma levels of atrial natriuretic factor in liver cirrhosis can be affected by various factors, such as ascites, renal function, use of diuretics drugs and dietary sodium intake. Moreover, the influence of high intra-abdominal pressure on cardiac atrial natriuretic factor release in patients with tense ascites has not been investigated. The aim of the present study was to evaluate the circulating levels of atrial natriuretic factor and their relationships to plasma renin activity, aldosterone concentration, and urinary sodium excretion in 45 cirrhotic patients divided into 4 groups: (a) cirrhotics without ascites; (b) nonazotemic cirrhotics with ascites; (c) cirrhotics with ascites and functional renal failure; and (d) cirrhotics with ascites taking diuretics. In some patients with tense ascites, atrial natriuretic factor was also measured after rapid abdominal relaxation by large volume paracentesis. Plasma levels of atrial natriuretic factor obtained in 13 healthy control subjects after 5 days on a 40-50 mEq sodium daily intake were 22.8 +/- 3.3 pg/ml. Mean plasma atrial natriuretic factor levels were normal in patients without ascites (35.1 +/- 11.4 pg/ml) and in those with ascites taking diuretics (27 +/- 9.2 pg/ml), but elevated in patients with ascites not taking diuretics (59.6 +/- 12 pg/ml) and in those with ascites and functional renal failure (58.5 +/- 16.6 pg/ml). These data show that plasma atrial natriuretic factor levels are elevated only in cirrhotic patients who are ascitic and not taking diuretics. In these patients atrial natriuretic factor levels were directly correlated with urinary sodium excretion, even though sodium balance was positive. This could be the consequence of the contrasting effects of antinatriuretic factors, as suggested by the inverse relationships between atrial natriuretic factor and urinary sodium on the one hand and plasma renin activity and plasma aldosterone concentration on the other. Twenty-six patients with tense ascites (12 taking diuretics and 14 not) were treated with rapid large-volume paracentesis (6500 +/- 330 ml of ascitic fluid removed in 168 +/- 16 min). At the end of the procedure, plasma atrial natriuretic factor levels had increased in all patients (from 45.5 +/- 10.1 to 100 +/- 17 pg/ml), whereas plasma renin activity and plasma aldosterone concentration had decreased (from 10.3 +/- 1.6 to 7 +/- 1.3 ng/ml/h, and 1160 +/- 197 to 781 +/- 155 pg/ml, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)     

Renal response to atrial natriuretic peptide in patients with advanced liver cirrhosis

Sodium retention in liver cirrhosis is thought to be due to, among other things, lack of a natriuretic factor or failure to respond to one. alpha-Human-atrial natriuretic peptide is a peptide that accounts partly or entirely for the circulating natriuretic activity in man. In the present study, we have evaluated the effects of the bolus administration of synthetic alpha-human-atrial natriuretic peptide (1 microgram per kg) to patients with liver cirrhosis and variable degrees of sodium retention. alpha-Human-atrial natriuretic peptide induced rapid and marked increases of diuresis and natriuresis in patients without sodium retention or with moderate retention. The results were comparable to those obtained in six healthy control subjects. Conversely, the diuretic and natriuretic effects of alpha-human-atrial natriuretic peptide were attenuated or completely blunted in patients with avid sodium retention. The two groups of patients differed not only in basal sodium excretion, but also in plasma renin activity and in plasma aldosterone levels, suggesting that the reduced responsiveness to atrial natriuretic peptide might be due to excessive antagonism by antinatriuretic factors. The direct relationship between baseline sodium excretion rate and that stimulated by human-atrial natriuretic peptide administration was consistent with this interpretation. In none of the subjects did plasma renin activity peptide and cortisol levels change after human-atrial natriuretic peptide, while plasma aldosterone slightly declined in cirrhotics. Blood pressure fell after the administration of the peptide, with the drug greater in cirrhotic than in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma human atrial natriuretic peptide levels in patients with liver cirrhosis

Plasma levels of human atrial natriuretic peptide (hANP) were investigated in patients with liver cirrhosis, and the relationships between plasma hANP levels and the following factors were studied: presence of ascites, serum and urine electrolytes, plasma renin activity, angiotensin I and II, aldosterone, catecholamines, prostaglandin derivatives, conventional liver function tests and circulating blood volume. Plasma hANP level was significantly (P less than 0.05) elevated in patients with ascites (mean = 58.6 pg/mL, s.e.m. = 8.8) compared with cases without ascites (mean = 36.6 pg/mL, s.e.m. = 2.6). With the disappearance of ascites, the level fell to normal in most cases. Urine sodium excretion was positively correlated with plasma hANP in patients without ascites, but not in patients with ascites. The plasma hANP level was disproportionately high for the rate of urinary Na excretion in cirrhotics with ascites. The plasma hANP level was not correlated with any of the other factors such as blood volume, renin-angiotensin-aldosterone levels, catecholamines and liver function tests. These results suggest that plasma hANP levels are elevated in cirrhotic patients especially with ascites, but the natriuretic response of the kidney to this raised hANP level can be impaired in patients with liver cirrhosis and ascites.     

Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease

BACKGROUND AND AIMS: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers of severity of liver disease, cardiac dysfunction, and hyperdynamic circulation in patients with cirrhosis. PATIENTS AND METHODS: Circulating levels of proBNP and BNP were determined in 51 cirrhotic patients during a haemodynamic investigation. RESULTS: Plasma proBNP and BNP were significantly increased in cirrhotic patients (19 and 12 pmol/l, respectively) compared with age matched controls (14 and 6 pmol/l; p<0.02) and healthy subjects (<15 and <5.3 pmol/l; p<0.002). Circulating proBNP and BNP were closely correlated (r = 0.89, p<0.001), and the concentration ratio proBNP/BNP was similar to that of control subjects (1.8 v 2.3; NS). Circulating proBNP and BNP were related to severity of liver disease (Child score, serum albumin, coagulation factors 2, 7, and 10, and hepatic venous pressure gradient) and to markers of cardiac dysfunction (QT interval, heart rate, plasma volume) but not to indicators of the hyperdynamic circulation. Moreover, in multiple regression analysis, proBNP and BNP were also related to arterial carbon dioxide and oxygen tensions. The rate of hepatic disposal of proBNP and BNP was not significantly different in cirrhotic patients and controls. CONCLUSION: Elevated circulating levels of proBNP and BNP in patients with cirrhosis most likely reflects increased cardiac ventricular generation of these peptides and thus indicates the presence of cardiac dysfunction, rather than being caused by the hyperdynamic circulatory changes found in these patients.     

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。     

Atrial natriuretic peptide, plasma renin activity, plasma volume, systemic vascular resistance and cardiac output in patients with cirrhosis

The present study aimed to assess relationships between plasma levels of atrial natriuretic peptide (ANP) and plasma volume, systemic vascular resistances, cardiac output and plasma renin activity in patients with cirrhosis. Thirty patients were included: eight with no history of liver disease were used as controls; 22 patients had biopsy-proven alcoholic cirrhosis without ascites (n = 11) and with ascites (n = 11). Mean ANP plasma level was significantly higher in both groups of cirrhotic patients than in controls (P less than 0.05). In the control group, ANP and plasma renin activity were inversely correlated (P less than 0.05) but no correlation was found in cirrhotic patients. In the group of patients with ascites, ANP plasma levels were inversely correlated to plasma volume (P less than 0.05) and to cardiac output (P less than 0.01) and directly correlated to systemic vascular resistances (P less than 0.01). Using multiple regression analysis, ANP remained correlated only with systemic vascular resistances (P less than 0.05). These results suggest that cirrhotic patients have high plasma levels of ANP whether or not they have ascites. In the light of current knowledge of ANP actions, the relationships between ANP plasma levels and plasma volume, cardiac output, and systemic vascular resistances are paradoxical in cirrhotic patients with ascites. ANP does not seem to play a critical role in the pathogenesis of sodium and water retention observed in these patients.     

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.     

Plasma Concentrations of Immunoreactive Atrial Natriuretic Peptide in Hospitalized Cirrhotic and Noncirrhotic Patients: Evidence for a Role of Deficient Atrial Natriuretic Peptide in Pathogenesis of Cirrhotic Ascites

Atrial natriuretic peptide(s) (ANP), are thought to be released from the cardiac atria in response to distension. If decreased effective circulating blood volume is important in pathogenesis of ascites, plasma ANP levels would be expected to be decreased in ascitic subjects because of decreased atrial distension. To test this hypothesis, we measured plasma ANP by competitive radioimmunoassay in three groups of fasted, supine hospitalized subjects: nine noncirrhotic control subjects, 12 cirrhotics without ascites, and 17 cirrhotics with moderate to marked ascites. Immunoreactive plasma ANP concentrations were 195 +/- 41, 171 +/- 31, and 137 +/- 34 pg/ml (m +/- SD), respectively, in the three groups. The mean concentration in the group with cirrhosis and ascites was significantly (p less than or equal to 0.01) les than those of the other two groups, which did not differ from one another. These results support the concept that decreased effective circulating volume plays a role in pathogenesis of cirrhotic ascites, and that a relative deficiency of ANP plays a role in the sodium retention of decompensated cirrhosis.     

Noninvasive assessment of spontaneous baroreflex sensitivity in patients with liver cirrhosis

Abstract: Aims/Background: An impairment of baroreceptor sensitivity has been found in liver cirrhosis. Noninvasive and spontaneous estimates of baroreflex sensitivity are obtained from beat-to-beat blood pressure and heart rate recordings by means of cross-spectrum analysis and calculation of alpha-index (as a measure of baroreflex gain). The aim of the present study was to investigate the function of the spontaneous baroreflex sensitivity related to clinical Child score in liver cirrhosis. Methods: The alpha-index was evaluated in 40 cirrhotic patients (18 with and 22 without ascites) and 17 healthy subjects by analysing finger arterial pressure recorded noninvasively with the Portapres device. Results: Baroreflex sensitivity was significantly lower in cirrhotic patients with and without ascites compared with healthy subjects (p<0.01). Furthermore, in patients with ascites the baroreflex gain was significantly related to plasma sodium (p<0.01). A significant inverse relationship was present between baroreflex gain and grade of Child score and the severity of ascites (p<0.01). There were no significant relationships between hormonal parameters (catecholamines, renin, aldosterone, arginine-vasopressin, atrial natriuretic peptide and nitric oxide) and baroreflex gain. No significant differences were found between healthy subjects and cirrhotic patients with respect to systolic and diastolic blood pressure total variability in a supine position, whilst it was lower in cirrhotic patients with ascites in a tilted position (p<0.05). Conclusion: Our findings showed that baroreflex sensitivity was significantly impaired in cirrhotic patients when compared with healthy subjects. In addition, there was a significant trend toward lower baroreflex sensitivity values with the grade score of Child class (p<0.01). Spectral analysis of the alpha-index provides viable alternatives to the pharmacological approach for estimation of baroreflex sensitivity and may represent a prognostic tool to identify cirrhotic patients at increased risk of adverse events.     

Plasma Levels of Atrial Natriuretic Peptide in Patients with Chronic Liver Disease

The plasma levels of atrial natriuretic peptide were determined by radioimmunoassay in 24 patients with chronic liver disease, including three patients with alcoholic liver disease, four with chronic active hepatitis, 13 with liver cirrhosis, and four with hepatocellular carcinoma. When compared with normal subjects (180 +/- 12 pg/ml), the plasma levels of atrial natriuretic peptide in cirrhotic patients (349 +/- 64 pg/ml) were significantly elevated (p less than 0.001) but not in other disease groups. In patients with chronic liver disease the plasma levels of atrial natriuretic peptide were correlated significantly with plasma renin activity but not with plasma aldosterone, and furthermore showed a negative correlation with indocyanine green disappearance rate. These results suggest that the increased plasma levels of atrial natriuretic peptide, which appear to be associated with an increase in plasma renin activity and with hepatic dysfunction, may participate in maintaining homeostasis of sodium and fluid volume in patients with chronic liver disease.     

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.     

The effect of beta-blocker on intractable ascites in cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma

BACKGROUND/AIMS: Intractable ascites is one of the serious complications after hepatectomy. Only little is known about their effect on postoperative ascites in patients with liver cirrhosis although beta-blockers have been used for cirrhotic complications including ascites. METHODOLOGY: Here, we report five cases of intractable ascites after hepatectomy, which were treated by propranolol (1 mg/kg/body). RESULTS: In three patients, plasma renin activity and aldosterone concentrations were markedly increased before propranolol administration, but fell to normal levels thereafter. Ascites subsided in all subjects except one, who developed cardiac dysfunction. CONCLUSIONS: Beta-blockers might be a promising drug for intractable ascites in cirrhotic patients undergoing hepatectomy.     

Effects of somatostatin on renal function in cirrhosis.

To investigate the renal effects of somatostatin in cirrhosis, renal function and plasma and urinary levels of endogenous neurohumoral vasoactive substances were measured in conditions of intravenous water overload (20 mL/kg body wt with 5% glucose) before and during the intravenous infusion of somatostatin (250-500 micrograms/h) in 6 cirrhotic patients without ascites and 17 nonazotemic cirrhotic patients with ascites. Somatostatin induced a significant reduction of renal plasma flow, glomerular filtration rate, and free water clearance in both groups of patients. In patients with ascites, somatostatin also reduced urinary sodium excretion. Changes in renal function were significantly more marked in patients with ascites than in those without ascites and occurred in the absence of changes in mean arterial pressure and plasma levels of renin, aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic peptide. Somatostatin induced a significant reduction in the plasma concentration of glucagon and urinary excretion of prostaglandin E2 that was not related to changes in renal function. These findings indicate that somatostatin administration induces renal vasoconstriction and impairs glomerular filtration rate, free water clearance, and sodium excretion in cirrhosis by a mechanism unrelated to systemic hemodynamics and endogenous neurohumoral vasoactive systems.     

肝硬变患者血浆内皮素和心钠素的变化

探讨内皮素(ET)与肝硬变水纳潴溜的关系。方法:应用放免法测定了血浆内皮素(ET)和心纳素(ANP)的含量。结果:①68例肝硬变患者血浆ET水平与正常人相比明显低下(P<0.01),按Child-Pugh分级,可见ET在伴腹水的患者下降明显(B、C级);②ET与门静脉直径呈负相关(r=-0.769,P<0.05),门静脉直径>1.6cm者与直径<1.6cm者相比,ET含量差异亦有显著性意义(P<0.01);③肝硬变患者ANP值明显高于正常对照组(P<0.01),且ANP与ET水平呈负相关(r=-0.786,P<0.01)。结论:ET水平与肝硬变严重程度密切相关,ET可能在腹水形成机制中发挥了重要作     

Variability of atrial natriuretic peptide plasma levels in ascitic cirrhotics: pathophysiological and clinical implications.

Ascitic cirrhotic patients are a heterogenous population with respect to factors that may affect plasma human atrial natriuretic peptide levels (such as degree of plasma volume and plasma levels of angiotensin II, vasopressin and norepinephrine). Thus the proven variability of plasma human atrial natriuretic peptide values in ascitic cirrhotic patients may be due also to the selection of patients, not only to the study conditions. The response to standardized stepped-care medical treatment of ascites makes it possible to characterize ascitic cirrhotic patients with different patterns of renal sodium excretion, intrarenal sodium handling, plasma renin activity, plasma aldosterone and thus, probably, effective circulating volume. Consequently, we evaluated human atrial natriuretic peptide plasma levels in controls (n = 23), in ascitic cirrhotic patients who underwent spontaneous diuresis (group A, n = 7) and in cirrhotic patients who required diuretic treatment (group B, n = 44). The last group was then divided into two subgroups. Subgroup B-R (n = 25) included patients who responded to spironolactone alone, whereas subgroup B-NR (n = 19) included patients who did not respond to 500 mg/day spironolactone. All patients were maintained on identical normocaloric restricted sodium intake (80 mEq/day) throughout the study. Ascitic cirrhotic patients, as a whole, had higher values of human atrial natriuretic peptide than did controls (70.8 +/- 46.6 pg/ml vs. 41.7 +/- 16.3 pg/ml, p < 0.025). No difference was found in human atrial natriuretic peptide/plasma renin activity between the two groups (87 +/- 160 pg/ng/hr vs. 44 +/- 73 pg/ng/hr, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.