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.     

Plasma levels of atrial natriuretic peptide in patients with liver cirrhosis and its relation to ascites and renal function

Plasma immunoreactive a-human atrial natriuretic polypeptide (Ir-α-hANP) was measured by radioimmunoassay in 21 cirrhotics and 10 normal subjects. Average of Ir-α-hANP level in cirrhotics was significantly higher than in normal subjects (125.8 ± 79.6 versus 28.7 ± 12.2 pg/ml, P< 0.001). In cirrhotics without ascites, Ir-α-hANP levels were positively correlated with creatinine clearance (Ccr) and urinary sodium excretion, suggesting that α-hANP was closely related to renal circulation and sodium homeostasis. One the contrary, in cirrhotics with ascites Ir-α-hANP levels were negatively correlated with Ccr. Urinary sodium excretion in cirrhotics with ascites and Ccr more than 50 ml/min was positively correlated with Ir-α-hANP levels. However, cirrhotics with ascites and Ccr less than 50 ml/min excreted little sodium in spite of high Ir-α-hANP levels. On the basis of the Ir-α-hANP before and after treatment of ascites, cirrhotics with ascites were subdivided into 2 groups. In group I Ir-α-hANP decreased from high values and in group II it was further elevated from slightly high values by treatment. The difference in renal function and plasma volume may account for the difference in Ir-α-hANP changes in the 2 groups. This study was presented in part in the 22nd meeting of the Japanese Association for the Study of the Liver, June 6,1986, Tokyo, Japan and in 22nd meeting of the European Association for the Study of the Liver, September 5, 1987, Torino, Italy.     

Plasma levels of atrial natriuretic peptide in patients with liver cirrhosis and its relation to ascites and renal function

Plasma immunoreactive alpha-human atrial natriuretic polypeptide (Ir-alpha-hANP) was measured by radioimmunoassay in 21 cirrhotics and 10 normal subjects. Average of Ir-alpha-hANP level in cirrhotics was significantly higher than in normal subjects (125.8 +/- 79.6 versus 28.7 +/- 12.2 pg/ml, P less than 0.001). In cirrhotics without ascites, Ir-alpha-hANP levels were positively correlated with creatinine clearance (Ccr) and urinary sodium excretion, suggesting that alpha-hANP was closely related to renal circulation and sodium homeostasis. On the contrary, in cirrhotics with ascites Ir-alpha-hANP levels were negatively correlated with Ccr. Urinary sodium excretion in cirrhotics with ascites and Ccr more than 50 ml/min was positively correlated with Ir-alpha-hANP levels. However, cirrhotics with ascites and Ccr less than 50 ml/min excreted little sodium in spite of high Ir-alpha-hANP levels. On the basis of the Ir-alpha-hANP before and after treatment of ascites, cirrhotics with ascites were subdivided into 2 groups. In group I Ir-alpha-hANP decreased from high values and in group II it was further elevated from slightly high values by treatment. The difference in renal function and plasma volume may account for the difference in Ir-alpha-hANP changes in the 2 groups.     

Plasma natriuretic peptide levels and daily physical activity in patients with pacemaker implantation.

To determine whether plasma ANP and/or BNP levels can be used to detect limitations in daily physical activity after pacemaker implantation, we measured plasma ANP and BNP levels at a pacemaker follow-up clinic in 56 patients (62+/-15 yrs, 2AAI, 9VVI, 34DDD, 7VDD and 4 rate-responsive modes), daily physical activity evaluated by a specific activity scale questionnaire (METs) and VO2 max obtained by expired gas analysis during ergometer exercise. A very close correlation (n=6, r=0.89, p<0.05) was obseved between. ANP in patients with daily physical activity class III (2-4 METs, n=21) was significantly higher than class II (5-6 METs, n=23, p<0.01) and class I (>7 METs, n=8, p<0.01), while BNP in class III patients was significantly higher than in class II (p<0.0001) and class I (p<0.0001) patients. Significant correlations between daily physical activity and BNP (r=-0.64, p<0.0001) and ANP (r=-0.43, p<0.001) were observed. Physiological pacing mode did not necessarily offer a better profile for BNP levels compared with non-physiological pacing modes. Patients with ventricular pacing (wide QRS: VDD, RR-VVI and VVI) showed significantly high ANP (p<0.01) and BNP (p<0.01) levels compared with those in patients with atrial pacing (narrow QRS: AAI and RR-AAI). During exercise, plasma catecholamines and ANP levels were significantly elevated, however, BNP levels, which were already elevated at rest, did not change significantly, and reflected a limitation of daily physical activity. The present study revealed that 37.5% of the patients displayed an elevation in BNP and this was judged to be a limitation of physical activity class III being equivalent to NYHA II or more. Elevated resting BNP levels reflected a limitation in daily physical activity in these patients. These findings suggested a third condition for physiological pacing--synchronization of ventricular contraction (narrow QRS pacing)--in addition to the two conventional conditions of atrioventricular synchrony and rate-responsiveness.     

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 levels of atrial natriuretic peptide in patients with chronic renal failure

Plasma levels of atrial natriuretic peptide (ANP) were measured in 57 patients with chronic renal failure (CRF) using a specific and sensitive RIA. The mean plasma ANP level in CRF patients [173 +/- 17.0 pg/ml (+/- SEM); n = 57] was significantly higher than that in normal subjects (37.6 +/- 1.9 pg/ml; n = 40). No significant correlation was found between plasma ANP and serum creatinine concentrations. CRF patients treated by maintenance hemodialysis had significantly higher plasma ANP levels than did nondialysis patients. Hemodialysis significantly decreased plasma ANP, and changes in plasma ANP levels after hemodialysis differed from those in serum creatinine concentrations. The mean serum creatinine concentration rose significantly 24 h after hemodialysis. In contrast, plasma ANP levels did not change in the first 24 h, but then rapidly increased. When ANP in predialysis plasma from patients with CRF was analyzed by reverse phase high performance liquid chromatography, the retention time of the main ANP peak coincided with that of synthetic human alpha ANP. These results suggest that expanded extracellular volume stimulates the secretion of ANP in CRF patients and that this increase in ANP release reflects a mechanism of compensation in volume homeostasis in man.     

Plasma levels of atrial natriuretic peptide in patients with Duchenne's progressive muscular dystrophy

To study the relationship between plasma alpha-atrial natriuretic peptide (alpha-ANP) and cardiac function in patients with Duchenne's progressive muscular dystrophy (DMD), we measured plasma alpha-ANP levels in 51 patients with DMD and evaluated them according to the clinical severity of the disease and the echocardiographic left ventricular function. In many of the patients with DMD, plasma alpha-ANP levels were mildly elevated, but no clear correlation was observed between alpha-ANP levels and wall motion abnormalities of the left ventricle. The alpha-ANP level was moderately or markedly elevated (81 to 120 pg/ml) in 3 of the 16 patients with respiratory failure and extremely high (1208 pg/ml) in the one patient with congestive heart failure. Two patients with respiratory failure and one with congestive heart failure, in whom alpha-ANP levels were elevated, died within 2 months. Elevation of left atrial pressure as a result of left ventricular dysfunction caused by impairment of the myocardium and elevation of right atrial pressure as a result of pulmonary hypertension caused by impairment of the respiratory muscles are considered to be involved in the mechanism of increased plasma alpha-ANP levels in patients with DMD. It can be concluded that a moderate or marked elevation in plasma alpha-ANP levels in patients with terminal DMD is a sign of a poor prognosis and may be a useful index for the management of the disease.     

慢性心力衰竭患者血浆肾上腺皮质激素及心钠素的含量及分析

目的:探讨慢性心力衰竭(CHF)患者血浆心钠素(ANP)、醛固酮(ALD)和皮质醇(COR)的含量变化及其意义。方法:检测54例CHF患者及16例同期住院无心衰患者的血浆ANP、ALD和COR含量,并评估血浆ANP 和ALD、COR的相关性。结果:CHF患者血浆ANP和ALD水平明显高于对照组(P<0.05),且与CHF程度有关, 而CHF患者血浆COR水平与对照组比较无显著性差异。CHF患者血浆ANP含量与ALD含量呈显著正相关(r= 0.474,P<0.001),而与COR含量无相关性(r=-0.071,P>0.05)。结论:血浆ANP和ALD含量有助于判断心衰的严重程度。     

Renal insensitivity to atrial natriuretic peptide in patients with cirrhosis and ascites. Effect of increasing systemic arterial pressure.

The IV infusion of pharmacological doses (0.05 microgram.kg-1.min-1) of atrial natriuretic peptide to 16 patients with cirrhosis and ascites induced a significant increase in sodium excretion (65 +/- 23 to 517 +/- 231 mu Eq/min), urine volume (10.7 +/- 2.3 to 15.7 +/- 3.7 mL/min), and glomerular filtration rate (89 +/- 4 to 110 +/- 4 mL/min) in only 5 patients (responders). No significant changes in these parameters (15 +/- 6 to 11 +/- 4 mu Eq/min, 5.5 +/- 1.0 to 4.2 +/- 1.1 mL/min, and 81 +/- 5 to 79 +/- 6 mL/min, respectively) were observed in the remaining patients (nonresponders). Compared with responders, nonresponders had significantly lower baseline sodium excretion (P less than 0.02), urine flow (P less than 0.05), free water clearance (2.5 +/- 0.9 vs. 6.9 +/- 2.1 mL/min; P less than 0.05), and mean arterial pressure (82 +/- 3 vs. 96 +/- 2 mm Hg; P less than 0.01) and significantly higher plasma renin activity (16.3 +/- 4.9 vs. 1.8 +/- 0.2 ng.mL-1.h-1; P less than 0.05) and aldosterone level (99 +/- 24 vs. 13 +/- 2 ng/dL; P less than 0.05). Atrial natriuretic peptide produced a similar reduction of arterial pressure in both groups. To investigate whether the blunted natriuretic response to atrial natriuretic peptide in nonresponders was caused by their lower arterial pressure, atrial natriuretic peptide was infused in 7 of these patients after increasing their arterial pressure to the levels of responders with nonrepinephrine. The increase in arterial pressure (from 81 +/- 5 to 95 +/- 5 mm Hg), which was not associated with significant changes in plasma renin activity and aldosterone concentration, did not reverse the blunted renal response to atrial natriuretic peptide in any of these patients. These results indicate that cirrhotic patients with blunted renal response to atrial natriuretic peptide are characterized by low arterial pressure, marked overactivity of the renin-aldosterone system, and severe sodium and water retention. Correction of hypotension without increasing effective blood volume does not restore renal insensitivity to atrial natriuretic peptide.     

Reciprocal changes in atrial natriuretic peptide levels and plasma renin activity during treatment of pulmonary embolism

We followed atrial natriuretic peptide (ANP) levels in 12 patients during anticoagulant treatment of pulmonary embolism. In each patient with this disorder ANP decreased during treatment. Concomitantly, plasma renin activity (PRA) markedly rose. The decrease in ANP was significantly related to the rise in PRA. No consistent changes in ANP or in PRA were observed in five patients with peripheral venous thrombosis receiving the same anticoagulant treatment. Plasma aldosterone levels did not change in either group.     

Plasma levels of brain natriuretic peptide increase in patients with idiopathic bilateral atrial dilatation

Idiopathic bilateral atrial dilatation (IBAD) is an extremely rare anomaly and is usually associated with atrial fibrillation. Plasma levels of atrial natriuretic peptide (ANP) have been shown to increase in patients with atrial fibrillation. However, secretion of ANP and brain natriuretic peptide (BNP) in patients with IBAD remains unclear. We investigated the clinical features of 9 patients with IBAD and 16 age- and sex-matched patients with lone atrial fibrillation (LAF). Plasma levels of ANP and BNP were measured, and echocardiographic parameters were followed. Left (LAV) and right atrial volumes (RAV) were significantly higher in patients with IBAD than in patients with LAF (both p < 0.01). There were no differences between patients with IBAD and LAF in other echocardiographic parameters. The percent increases in LAV and RAV in patients with IBAD exceeded those in patients with LAF (both p < 0.01). Plasma levels of BNP and the BNP/ANP ratios in patients with IBAD were significantly higher than those in patients with LAF (both p < 0.01), but there was no significant difference in plasma levels of ANP. Regarding the clinical course of the patients with IBAD compared with those with LAF, the atrial volume increased gradually, and plasma levels of BNP were significantly higher. These findings suggested that IBAD was not only influenced by long-term atrial fibrillation, but also by subclinical left ventricular dysfunction.     

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.     

Plasma brain natriuretic peptide levels indicating thromboembolism in very elderly patients with non-valvular atrial fibrillation.

BACKGROUND: Assessment of left atrial (LA) function by transesophageal echocardiography is useful for detecting patients with a high risk thromboembolism secondary to atrial fibrillation (AF). A recent study showed that the atrium is the main source of brain natriuretic peptide (BNP) in AF patients without overt heart failure. The purpose of this study was to assess the possible relationship between LA function and plasma BNP levels in very elderly patients with non-valvular AF. METHODS AND RESULTS: Seventy-four consecutive patients with chronic non-valvular AF (aged, 82+/-6 years) underwent transthoracic and transesophageal echocardiography and measurement of plasma BNP. Thirteen AF patients who had a history of cerebral embolism or echocardiographic evidence of thrombus (TE+ group) were compared with 61 AF patients who had no such complications (TE- group). The TE+ group demonstrated a lower LA appendage (LAA) velocity and higher plasma BNP level than the TE- group. Assessment of variables by multiple logistic regression analysis revealed that BNP was a significant predictor of thromboembolism. There was a significant negative correlation between the plasma BNP level and the LAA peak flow velocity. CONCLUSIONS: The present findings would suggest the usefulness of measuring plasma BNP to detect very elderly non-valvular AF patients at high risk for thromboembolism.     

Natriuretic response to the combination of atrial natriuretic peptide and terlipressin in patients with cirrhosis and refractory ascites

Background/Aims: Refractory ascites, which occurs in certain patients with cirrhosis, is associated with a blunted natriuretic response to exogenous atrial natriuretic peptide (ANP). Since this blunting seems to be related to ANP-induced arterial hypotension, a vasoconstrictor, such as terlipressin (a vasopressin analogue), may restore natriuresis to exogenous ANP. Moreover, since cirrhosis-elicited vasolidation is thought to play a role in sodium retention, a vasoconstriction caused by terlipressin alone may lead to an increase in sodium excretion. This study aimed to evaluate the natriuretic response to either a combination of ANP with terlipressin or terlipressin alone in patients with cirrhosis and refractory ascites.Methods: Sixteen consecutive patients with cirrhosis and refractory ascites were randomly assigned to receive either a combination of terlipressin (1–2 mg, i.v. bolus) with ANP (35 ng/kg, i.v. bolus followed by 15 ng·kg⁻¹·min⁻¹ for 60 min) (n=8) or terlipressin alone (1–2 mg, i.v. bolus) (n=8). Sodium excretion and urine output, systemic, splanchnic and renal hemodynamics and renal oxygen consumption were measured before and during treatments.Results: Combined therapy did not change arterial pressure but significantly increased urinary sodium excretion and urine output. These effects were associated with a significant increase in glomerular filtration rate and a decrease in renal oxygen consumption. Terlipressin alone significantly increased arterial pressure but did not change urinary sodium excretion or urine output. Moreover, terlipressin did not change either glomerular filtration rate or renal oxygen consumption.Conclusions: The combination of exogeneous ANP with terlipressin, but not terlipressin alone, increases sodium excretion in patients with cirrhosis and refractory ascites.     

心房颤动患者血浆心房钠尿肽与C型钠尿肽浓度的变化

目的观察心房颤动(简称房颤)患者血浆心房钠尿肽(ANP)和C型钠尿肽(CNP)水平的变化,及其与心脏结构改变的相关性,从而进一步分析ANP、CNP在房颤心房结构重构中的作用。方法入选左心功能正常的房颤患者及无房颤对照组。房颤患者又根据房颤持续时间不同分为阵发性房颤(Paf)组及持续性房颤(Peaf)组。采用酶联免疫吸附法检测血浆ANP和CNP水平,并采用超声心动图测量舒张期左房内径、左室内径、室间隔厚度及左室后壁厚度,并计算左室质量指数。结果入选对照组57例,和房颤组62例(其中Paf组35例,Peaf组27例)。年龄、性别等临床背景资料均无差异,具有可比性。房颤组的血浆ANP和CNP水平明显高于对照组[ANP:(728.1±336.9)pg/ml vs(524.6±165.3)pg/ml,P=0.000;CNP:(114.2±28.6)pg/ml vs(97.1±22.4)pg/ml,P=0.000],且与左房内径明显正相关(ANP:r=0.389,P=0.001;CNP:r=0.344,P=0.004)。此外,ANP与CNP之间呈明显的相关性(r=0.799,P=0.000),CNP与室间隔厚度(r=0.343,P=0.006)、左室后壁厚度(r=0.308,P=0.013)、左室质量指数(r=0.275,P=0.030)相关。结论 ANP和CNP与左房扩大明显相关,可能参与心脏重构的过程。     

Plasma atrial natriuretic peptide levels for predicting the outcome of atrial fibrillation.

The predictive value of plasma atrial natriuretic peptide (ANP) on the cardioversion outcome was evaluated in 46 hospitalized patients with recent-onset atrial fibrillation (AF). Cardioversion was successful in 42 (91%) patients, 7 (15%) of them regained sinus rhythm spontaneously. After 12 months, 14 (33%) cardioverted patients were in chronic AF. There were no differences in plasma ANP levels between groups where cardioversion failed, those who cardioverted but later developed chronic AF or those who remained in sinus rhythm. However, among patients who were on antiarrhythmic therapy, ANP levels obtained after cardioversion were lower in those who later remained in sinus rhythm. We conclude that lower ANP after cardioversion may be associated with increased chances of long-term preservation of sinus rhythm.