Atrial natriuretic peptide in liver cirrhosis with mild ascites

To clarify the involvement of atrial natriuretic peptide (ANP) in the pathogenesis of liver cirrhosis, we measured plasma ANP in patients with various stages of cirrhosis and in age-matched normal subjects. Urinary cyclic guanosine monophosphate (cGMP) was also measured as a marker of active biological ANP. In addition, effects of exogenous synthetic human ANP (0.5 Μg/kg) on renal functions were examined in normal subjects and in cirrhotics without ascites or with mild ascites. Plasma ANP levels were not significantly different among these 3 groups. Urinary cGMP concentrations were significantly higher in both cirrhotics without ascites and cirrhotics with mild ascites, (340 pmol/ml, P<0.05 and 496 pmol/ml, P<0.01 respectively) than normal subjects (95 pmol/ml). In normal subjects, marked increases in urinary volume (UV), sodium excretion (UNaV), fraction excretion of sodium (FENa) and free water clearance (CH₂O) were induced after ANP infusion, and significant recoveries were subsequently observed in these parameters. However, in cirrhotics, the responses to ANP infusion of UV, FENa and CH₂O were far less dramatic. The response of UV, UNaV and FENa in cirrhotics with mild ascites was delayed compared to cirrhotics without ascites. These results suggest that the blunted natriuretic responsiveness to ANP is contributory to the pathogenesis of initial sodium retention in cirrhotics. This study was presented in part in the 25th annual meeting of the Japanese Association for the Study of the Liver, June, 1, 1989 Kanazawa, Japan.     

Atrial natriuretic peptide in alcoholic cirrhosis

Sodium retention in cirrhosis could result from a deficiency of atrial natriuretic peptide (ANP) or end-organ resistance to ANP. Venous levels of α-human ANP (αhANP) measured in 19 alcoholic cirrhotics by radio-immunoassay were in the higher end of the normal range (29.7 pg/ml, s.d. = 17.2) and tended to increase with development of ascites or varices. Arterial levels of αhANP were not related to right atrial pressure but were related inversely to pulse rate. There was significant splanchnic (mean = 37.2%, s.d. = 19.5) and non-splanchnic clearance (mean = 30.3%, s.d. = 17.1) of αhANP. The percentage extraction of αhANP across the splanchnic bed (%E ANP splanchnic) was not related to portal pressure, effective hepatic plasma flow or degree of intrahepatic shunting. The %E ANP splanchnic increased as functional liver cell mass (antipyrine clearance) decreased (r= 0.592, P= 0.034). Despite increased splanchnic clearance, αhANP levels increased with a fall in functional liver cell mass presumably due to increased release. Renal sodium retention in cirrhosis does not involve a deficiency of αhANP but increased end-organ resistance needs to be excluded.     

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.     

血浆、腹水中心钠素、加压素的测定及意义

本文采用放射免疫分析法测定25例肝硬化腹水患者血浆、腹水中心钠素和加压素的水平，发现血浆，腹水中心钠素水平相当，均明显高于正常血浆水平；血浆加压素升高不明显，而腹水中加压素浓度显著高于血浆。结果提示心钠素和加压素的分泌释放异常，在肝硬化钠，水潴留及腹水形成中有一定的作用。腹水中高浓度的心钠素和加压素通过腹水回输可能起到一定的治疗作用。     

B-type natriuretic peptide levels in patients with paroxysmal lone atrial fibrillation

To investigate the levels of B-type natriuretic peptide (BNP) in patients with atrial fibrillation (AF) but without structural heart disease, we measured plasma BNP concentration in 61 consecutive AF patients and in 61 age- and sex-matched healthy subjects. Plasma BNP concentration in the AF group was significantly higher than in the control group (121 ± 32 vs 41 ± 12 pg/ml, P < 0.001). Logistic regression analysis showed that age (r = 0.66, P < 0.001), left atrial diameter (r = 0.59, P < 0.01), and a history of AF (r = 0.72, P < 0.001) were independent predictors of elevated BNP. We concluded that BNP was elevated in patients with paroxysmal lone AF. The clinical significance of BNP elevation in these patients requires further investigation.     

短期静脉内注射重组人心钠肽对急性心力衰竭患者血流动力学的影响

目的:观察短期静脉内注射国产重组人心钠肽(rhANP)治疗难治性心力衰竭(RHF)患者血流动力学效应及安全性。方法:连续入选住院的RHF患者10例,常规急性HF药物强化治疗无明显改善,开始静脉内给予rhANP0.1μg.kg-1·min-1持续静脉泵入60min。在给药24h内,监测有创血流动力学参数、血压、HR及血清生化指标。结果:在注射rhANP0.5h时,肺毛细血管楔压(PCWP)、平均肺动脉压(MPAP)、中心静脉压(CVP)、体循环阻力(SVR)、肺循环阻力(PVR)较基础值明显下降[PCWP(15.67±4.55):(24.00±4.00)mm Hg(1mm Hg=0.133kPa),P<0.05;MPAP(25.67±6.62):(34.33±7.92)mm Hg,P<0.05;CVP(9.50±3.99):(13.00±3.29)mm Hg,P<0.05;SVR(1121.50±138.64):(1603.67±422.74)dynes×s/cm5,P<0.05;PVR(166.00±57.00):(226.83±74.24)dynes×s/cm5,P<0.05],心指数较基础值明显升高[(3.22±0.35):(2.50±0.38),P<0.05]。这种有益的血流动力学效应可持续到注射后24h。收缩期血压在给药后1h下降最明显(P<0.01),以后恢复至基线时水平。HR、血钾、血钠、血肌酐无明显变化。未发现与rhANP相关的症状性低血压及其他严重不良反应。结论:短期静脉内给予国产rhANP能迅速而持续地改善RHF患者的血流动力学状况,且安全可行。     

Brain natriuretic peptide and severity of disease in non-alcoholic cirrhotic patients

BACKGROUND: Cirrhotic patients have a hyperdynamic systemic circulation. They have insidious cardiac problems besides well-known complications. Brain natriuretic peptide (BNP) relaxes vascular smooth muscle and has a portal hypotensive action. The relations between BNP levels and severity of disease, cardiac dysfunction and esophageal varices were studied in non-alcoholic cirrhotic patients. METHODS: Fifty-two non-alcoholic cirrhotic patients were evaluated for decompensation component of cirrhosis. The BNP concentration of echocardiographically examined patients was determined. RESULTS: The BNP levels were significantly higher in ascites, spontaneous bacterial peritonitis and hepatic encephalopathy history group (P = 0.033, P < 0.001, P = 0.014, respectively), but no significant difference were observed for presence of esophageal varices and bleeding history (P = 0.267, P = 0.429). A significant correlation was observed between BNP concentration and Child score (r = 0.427, P = 0.012), interventricular septal thickness (r = 0.497, P < 0.001) and left ventricular posterior wall thickness (r = 0.526, P < 0.001). According to Child-Pugh classification there were no significant difference between groups for echocardiographic measurements and blood pressure (P > 0.05), but plasma BNP levels were significantly higher in Child class B and C patients compared with class A patients (P < 0.05). CONCLUSION: Increased levels of BNP are more likely related to the severity of disease in non-alcoholic cirrhotic patients. The advanced cirrhosis is associated with more advanced cardiac dysfunction and BNP has prognostic value in progression of cirrhosis.     

Increased plasma levels of atrial natriuretic peptide in patients with congestive heart failure

Atrial natriuretic peptide (ANP) is a recently discovered hormone,originating from atrial myocardium. The peptide (or family ofpeptides) induces potent diuretic/natiuretic, vasorelaxing andaldosterone inhibitory effects. We have investigated plasmaconcentrations of immunoreactive ANP in 10 patients with congestiveheart failure (CHF). Mean plasma ANP concentrations were morethan three times higher in CHF patients than in a matched controlgroup. High plasma ANP concentrations in pathophysiologicalconditions with a high preload combined with salt and waterretention is consistent with a physiological role of this hormoneto correct hypervolemia by causing natriuresis and diuresis.It is concluded that ANP homeostasis is altered in patientswith CHF and that this hormone may be of importance in the pathophysiologyof CHF.     

Plasma brain natriuretic peptide and atrial natriuretic peptide concentrations correlate with left ventricular end-diastolic pressure

The present study was designed to investigate whether brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations correlate with left ventricular end-diastolic pressure (LVEDP), pulmonary capillary wedge pressure (PCWP), diastolic pulmonary arterial pressure (DPAP), right atrial pressure (RAP), or ejection fraction (EF). Plasma BNP and ANP levels were determined by commercial radioimmunoassays (Peninsula) after Sep Pak C₁₈ extraction in blood samples withdrawn from the pulmonary artery and the left ventricle or from the left ventricle and the femoral vein in 85 patients undergoing diagnostic cardiac catheterization. Linear and nonlinear regression analysis and the paired sample f-test were applied to the data. Pulmonary arterial plasma BNP and ANP levels showed a close nonlinear correlation with LVEDP (BNP: r=0.94, p < 0.001; ANP: r=0.81, p < 0.001), a significant linear correlation with PCWP, DPAP, and RAP, and a significant negative correlation with EE ANP concentrations decreased significantly from the pulmonary artery to the left ventricle and from the left ventricle to the femoral vein (p < 0.001). BNP levels also decreased significantly between the left ventricle and the femoral vein (p < 0.001), but there was no significant difference between pulmonary arterial and left ventricular BNP concentrations. BNP and ANP concentrations correlated significantly between pulmonary arterial and left ventricular blood samples (BNP: r = 0.99, ANP: r = 0.93, p < 0.001) and between left ventricular and peripheral blood samples (BNP: r=0.99, ANP: r=0.94, p<0.001). The present data suggest that peripheral plasma BNP and ANP levels are useful noninvasive indices of cardiac performance.     

老年肺心病患者血浆内皮素,心钠素测定及临床意义

目的测定老年肺心病患者血浆内皮素（ＥＴ）、心钠素（ＡＮＰ）水平及探讨其临床意义。方法用放射免疫法测定健康老年人、非老年肺心病及老年肺心病患者各３０例不同时期血浆ＥＴ及ＡＮＰ水平。结果老年肺心病患者急性加重期及缓解期ＥＴ分别为３０４±８３及１３２±４１ｐｇ／ｍｌ，ＡＮＰ分别为３１９±９０及２３５±８４ｎｇ／ｍｌ，较健康对照组明显升高（Ｐ值＜０．０１或０．００１）。肺心病合并Ⅱ型呼吸衰竭者ＥＴ、ＡＮＰ分别为３８４±６６及３８４±７８ｎｇ／ｍｌ，明显高于合并Ⅰ型呼吸衰竭者（Ｐ值＜０．０５）。同期测定的３０例非老年肺心病患者血浆ＥＴ与ＡＮＰ水平与老年患者差异无显著性（Ｐ值＞０．０５）。直线相关分析表明，血浆ＥＴ与ＡＮＰ之间无显著性相关性。结论肺心病患者血浆ＥＴ、ＡＮＰ含量增高可能参与疾病的发生与发展过程，但在肺心病情况下，两者之间无显著相关关系     

Longstanding atrial fibrillation causes depletion of atrial natriuretic peptide in patients with advanced congestive heart failure

BACKGROUND: Congestive heart failure (CHF) is characterized by neurohormonal activation, including increased plasma concentrations of atrial natriuretic peptide (ANP) and N-terminal ANP (N-ANP). Onset of atrial fibrillation (AF) further increases these peptides, but it may be hypothesized that concentrations decrease during longstanding AF due to inherent atrial degeneration. AIM: We sought to investigate the relation between neurohormonal activation in patients with CHF and the duration of concomitant AF. METHODS: The study group comprised 60 patients (age 70 +/- 8 years) with advanced CHF due to left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) < 0.35) and chronic AF (duration 21 (1-340) months). Plasma neurohormone concentrations were measured, and multiple regression analysis was performed to identify their clinical predictors. RESULTS: Median plasma neurohormone concentrations were: ANP 113 pmol/l, N-ANP 1187 pmol/l, norepinephrine 496 pg/ml, renin 127 micro units/l, aldosterone 128 pg/ml and endothelin 8.1 pg/ml. Norepinephrine, renin, aldosterone and endothelin were not significantly related to the duration of AF. In contrast, ANP decreased along with the duration of AF (P = 0.03), while the same trend was observed for N-ANP (P = 0.10). However, for these peptides a first order interaction with LVEF was present, which was not observed in the other neurohormones. In patients with LVEF > 0.25 ANP and N-ANP increased along with the duration of AF, whereas in patients with LVEF < or = 0.25 an inverse relation between ANP (P = 0.02) and N-ANP (P = 0.04) and the duration of AF was present, longer-standing AF being associated with lower concentrations. CONCLUSION: In patients with advanced CHF with low LVEF plasma ANP and N-ANP concentrations decrease during longstanding AF. This finding agrees with the concept that longstanding AF leads to impaired ability of the atria to produce these neurohormones due to inherent degenerative changes.     

Circulating atrial natriuretic peptide (ANP) and central blood volume (CBV) in cirrhosis

ABSTRACT— Endogenous α-atrial natriuretic peptide (ANP) in plasma is elevated in various hypervolaemic conditions. Possible relationships between circulating immunoreactive ANP and cardiovascular and splanchnic haemodynamics were therefore studied in patients with cirrhosis (n = 16) and controls (n = 12). Arterial plasma concentration of ANP in supine patients was (mean ± SEM) 33 ± 4 vs 41 ± 10 pg/ml (9.9 ± 1.2 vs 12.3 ± 3.0 fmol/l) in controls (n.s.), and there was a weak direct correlation with right atrial pressure (r = 0.36, P = 0.05). There was no relationship with the presence of ascites or diuretic treatment. Central blood volume (CBV, i.e. the blood volume in the heart cavities, lungs, and aorta), determined from the mean transit time of ¹²⁵I-labelled albumin and cardiac output, was significantly reduced in cirrhotics compared to controls (1.45 ± 0.12 vs. 1.83 ± 0.10 1, P < 0.02) and inversely correlated with portal pressure (r = –0.42, P < 0.05), whereas total plasma volume was somewhat increased (3.51 ± 0.2 vs 3.19 ± 0.2, 0.05 < P < 0.1). A high arterio-venous extraction of ANP was found in the splanchnic system (extraction ratio 0.44 vs 0.28), kidney (0.45 vs 0.54), lower limb (0.53 vs 0.40), and forearm (0.27 vs 0.18) in patients and controls, respectively (n.s.). Our results suggest that the lack of elevation of circulating ANP in cirrhosis, even in the presence of actual fluid retention, may be explained by central hypovolaemia in these patients. Turnover and degradation of ANP is rapid and normal, as evaluated from the tissue extraction ratios.     

急性心肌梗死KillipⅡ级患者经皮冠状动脉介入治疗后血浆脑钠素、心钠素水平的变化

目的研究急性心肌梗死(acutemyocardialinfarction,AMI)伴左心力衰竭患者经皮冠状动脉介入治疗(PCI)后心钠素(atrialnatriureticpeptide,ANP)和脑钠素(brainnatriureticpeptide,BNP)二种因子的变化及其临床意义。方法入选AMIKillipⅡ级患者40例作为试验组,在AMI1周内行PCI治疗,另入选AMIKillipⅡ级未行PCI治疗患者40例作为对照组。试验组患者于AMI48h内,PCI术后24h,术后1个月时,对照组患者在相对应的时间,采集肘静脉血,采用酶联免疫吸附法分析,测血浆ANP及BNP水平。结果两组间ANP、BNP水平比较,试验组患者AMI48h内,血浆ANP、BNP水平均与对照组相似,两者间无显著性差异(P>0.05)。PCI术后24h,术后1个月ANP、BNP水平均较对照组明显降低,两组间有显著性差异(P<0.05);组内比较,试验组患者PCI术后24hANP、BNP水平较AMI48h内减低,但两者间无显著性差异(P>0.05);PCI术后1月ANP、BNP水平较术前明显回落,两者有显著性差异(P<0.05)。对照组患者在相对应的PCI术后24h,术后1个月这一时限ANP、BNP水平较AMI48h内无明显变化(P>0.05)。结论本研究发现AMIKillipⅡ级患者经PCI治疗可使血浆ANP、BNP水平降低。     

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。     

重组人心钠肽对急性心力衰竭患者血流动力学及神经内分泌激素的影响

目的观察重组人心钠肽（rhANP）治疗急性心力衰竭患者的血流动力学效应，神经内分泌激素的变化及安全性。方法连续入选住院的20例急性心力衰竭患者，静脉内给予rhANP以0．1μg·kg。^-1·min^-1持续静脉泵入60min，监测24h的有创血流动力学参数、监测给药0h和36h的血浆肾素、血管紧张素、醛固酮以及去甲肾上腺素的水平，并监测收缩期血压、心率及血清生化指标。结果在注射rhANP0．5h时，肺毛细血管楔压、平均肺动脉压、中心静脉压、体循环阻力、肺循环阻力较基础值明显下降（P〈0．05），心指数较基础值明显升高（P〈0．05），这种有益的血流动力学效应可持续到24h；血浆肾素、血管紧张素、醛固酮以及去甲肾上腺素的水平均明显下降（P〈0．05）；收缩压在给药1h下降（P〈0．01），以后恢复至基线时水平。观察无严重不良反应发生。结论静脉内注射rhANP能迅速地改善急性心力衰竭患者的血流动力学状况，能够抑制神经内分泌激素的激活，且安全可行。     

Atrial natriuretic peptide response to postural changes in patients with left atrial hypertension

Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate(GMP) and renin activity (PRA) were measured in 13 patientswith mitral stenosis 24 h before and 48 h after balloon valvotomyresulting in a fall in LA pressure from 23.4 ± 2.2 to10.5 ± 0.8 mmHg (P<0.01). Before treatment, plasmaANP was higher during ambulation (128.1 ± 18.5 pg ml^–1)than in the supine posture (93.3± 15.0 pg ml^–1;P<0.01) and did not diminish after return to the erect posture(86.4± 14.1 pg ml^–1). A physiological responsewas restored after valvotomy with ANP plasma levels of 49.2± 7.8pg ml^–1 in the initial ambulant period, 63.1± 12.6 pg ml^–1 in the supine posture and 44.6 ±8.7 pg ml^–1 in the final erect posture. Postural variationsof cyclic GMP were parallel to those of ANP. In contrast, LAhypertension did not abolish PRA postural response. During thethree successive periods of ambulation, supine posture and erectposture PRA was 5.4± 10, 2.8 ± 0.6 and 5.5±1.2ng h^–1 ml^–1, respectively, before treatment,whereas after treatment the values measured were 10.3 ±2.9, 2.3 ± 0.7 and 7.0 ± 2.5 ngh^–1 ml^–1respectively. Variations of plasma ANP, cyclic GMP and PRA inresponse to postural changes were also studied in 10 healthyvolunteers and in 12 uraemic patients with high plasma ANP.Similar physiological results were obtained in these two controlgroups, suggesting that the dysregulation of ANP response inpatients with high LA pressure was not related to the high valuesof plasma ANP. In conclusion, persistent elevation of plasmaANP in response to postural changes appears to be the consequenceof LA hypertension.     

Brain natriuretic peptide increases acutely and much more prominently than atrial natriuretic peptide during coronary angioplasty

BACKGROUND: Increased levels of plasma brain natriuretic peptide (BNP) are observed in patients with congestive heart failure, hypertension, left ventricular hypertrophy, and acute myocardial infarction. However, there are no data on serial changes in plasma levels of BNP in patients undergoing coronary angioplasty. HYPOTHESIS: The study was undertaken to examine plasma concentrations of BNP together with those of atrial natriuretic peptide (ANP) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). METHODS: Plasma concentrations of BNP and ANP were examined in 13 patients with stable angina pectoris and good left ventricular function undergoing PTCA. Blood samples were taken from the femoral vein at baseline, after the first balloon inflation, after the end of the procedure, and 4 h thereafter. RESULTS: Plasma BNP levels were 14 +/- 4 at baseline, 22 +/- 10 after the first balloon inflation, 28 +/- 12 at the end of the procedure, and 15 +/- 4 pgr/ml 4 h thereafter (F = 13.05, p < 0.00001). Plasma ANP levels were 80 +/- 15, 86 +/- 14, 90 +/- 24, and 75 +/- 6 fmol/l (F = 5.95, p = 0.002), respectively. The increase of BNP at the end of the procedure was related to the increase of ANP (r = 0.78, p = 0.002). CONCLUSION: Plasma BNP levels increase acutely and much more prominently than those of plasma ANP during coronary angioplasty; however, plasma BNP levels return to baseline values shortly after the end of the procedure.     

Low plasma concentrations of atrial natriuretic peptide in untreated hypothyroid patients

A group of patients with primary hypothyroidism has been studied, and it is reported that low serum levels of thyroid hormones are accompanied by low plasma atrial natriuretic peptide (ANP) concentrations. While the correlation between ANP and thyroid hormone levels is strong, no correlation was found between ANP and heart rate or arterial blood pressure. It is suggested that thyroid hormones directly stimulate the release of ANP from atrial cardiocytes.