Plasma BNP Levels Research Articles

Does hypoxia directly regulate the natriuretic peptide system?

We read with great interest the letter by Costantino et al. [1] published recently in International Journal of Cardiology. In the paper they reported the time course of B-type natriuretic peptides after ventricular fibrillation (VF) and showed that the levels of both B-type natriuretic peptides increased after VF. Based on the previously published results they refer to that the mechanisms behind VF-induced increases in plasma BNP levels are cardiac myocyte stretching and arrhythmias.

Abstract 17849: Additional Use of Methotrexate Improved Clinical Findings and Metabolic Profile in Patients with Cardiac Sarcoidosis Refractory to Corticosteroids

Background. Corticosteroids are indicated in cardiac sarcoidosis (CS). However, some patients worsen clinically despite corticosteroid treatment, and are suffering from steroid-related side effects. Methotrexate (MTX) is one of the most commonly used cytotoxic agents and has steroid-sparing effects for autoimmune diseases. Furthermore, aniti-inflammatory property of this agent may affect the pathogenesis of chronic heart failure. We hypothesized that MTX has a potential to improve clinical findings and reduce side effects of corticosteroids in patients with refractory CS. Methods. Out of 30 ambulatory CS patients treated with corticosteroids, we added MTX in combination with maintenance dose of corticosteroids for 7 patients who were suffering from relapse or deterioration and steroid-related side effects such as poorly controlled diabetes, osteoporosis or psychosis. All of the 7 were treated with 7.5mg of MTX once a week. A mean duration of corticosteroid treatment in the 7 patients was 61 months (32 to 95 months). Results. During a mean follow-up of 30 (12 to 46) months, no cardiac event and no major side effect occurred. The addition of MTX reduced maintenance steroid doses without further deterioration (8.3±3.4 to 6.4±2.2mg, p<0.05) during the follow-up periods. Although LVEF was not significantly increased, plasma BNP level was significantly decrease from 120±106 to 75±68pg/ml (p<0.05). There were significant improvements in diabetes (HbA1c:7.6±1.9 to 7.2±2.0%, p<0.05) and lipid profile (Triglyceride levels: 226±124 to 167±118mg/dl, p<0.05). Increased uptake of 99m Tc-sestamibi and decreased uptake of 67 Ga in the myocardium were clearly observed in 2 patients after the addition of MTX. Conclusion. MTX is safe and helpful in combination with corticosteroids improving clinical findings, allowing for lower steroid doses, and reducing side effects of corticosteroids in patients with CS.

The clinical significance of urinary B-type natriuretic peptide assay for the diagnosis of chronic heart failure

Objective To investigate the value of urinary BNP for diagnosis of chronic heart failure (CHF). Methods The levels of Urinary BNP and plasma BNP were measured by microparticle enzyme immunoassay (MEIA) in 83 patients with CHF and 30 control subjects. The heart function was classified according to the NYHA criteria. Left ventricular ejection fractions (LVEF) were measured by echocardiology. Results The level of urinary BNP in patients with CHF was[90. 0(38. 3 -209. 5 )]ng/L and the level of plasma BNP was[680. 0 ( 289. 7 - 1543.5)]ng/L, both of them were much higher than those in healthy subjects,[17. 0 ( 13.0 - 33. 0)]ng/L and[84. 5 ( 56. 0 - 158.0 )]ng/L, respectively (P＜0. 01 ). The concentrations of urinary BNP increased gradually with more severe symptoms ( NYHA cl ass Ⅰ -ⅣV ). The level of urinary BNP was positively correlated with NYHA class ( r = 0. 742, P ＜ 0. 01 )and the level of plasma BNP (r =0. 842,P ＜0. 01 ) while negatively related with LVEF (r = -0. 801 ,P ＜0. 01 ). The level of urinary BNP in patients with LVEF ＜ 40％ was[143.0 ( 85. 0 - 258.0)]ng/L , which was much higher than that in patients with LVEF≥40％ ,[31.5( 17.3 -38. 8)]ng/L, (P ＜0. 01 ). At a decision threshold of 36. 5 ng/L, the urine BNP assay demonstrated a clinical sensitivity and specificity of 84％ and 80％ ,respectively. In this study,the area under the curve(AUC) was 0. 905. Conclusion Urinary BNP is a new candidate marker for the diagnosis of CHF,it provides a similar accuracy with plasma BNP. Key words: Heart failure; Natriuretic peptide, brain; Urinalysis

Effects of Oral Tolvaptan Administration in Patients Hospitalized for Chronic Heart Failure with Preserved Ejection Fraction and Chronic Kidney Disease

age 81 years. Results: During the 24 hours, urine output was significantly increased (12546615 to 19636777ml, p50.018), and serum sodium levels tended to be increased (136.164.5 to 137.866.1mEq/L, p50.055), although there were no significant changes in blood pressure and serum potassium levels. Body weight was significantly decreased by the 5 days after Tolvaptan administration (51.069.8 to 49.368.9kg, p50.005). There were significant decreases in plasma BNP levels (7056790 to 3826401pg/mL, p!0.0001) and pressure gradient from tricuspid regurgitation (47.369.3 to 31.5610.7mmHg, p!0.0001) 7 days after the administration, although serum creatinine levels were unchanged. There were 3 adverse events (liver dysfunction, worsening diabetes and Torsades de pointes). Conclusions: A small dose of tolvaptan is well tolerated and helpful for diuresis in the elderly patients with decompensated heart failure requiring repetitive hospitalization.

Clinical Factors Associated with Elevation of Plasma BNP Level in Elderly Patient Without Heart Disease

Clinical Factors Associated with Elevation of Plasma BNP Level in Elderly Patient Without Heart Disease

Effects of long-term proBNP cardiac gene delivery in experimental hypertensive heart disease

Results In SHR, a single systemic administration of AAV9 vector allowed longterm, cardiac BNP overexpression with an increase in plasma BNP levels as compared with untreated SHR (433.3±17 vs 60.6±15* pg/ml). This further resulted in reductions in systolic (121±11 vs 184 ±13* mm Hg) and diastolic (103±5 vs 148±24* mm Hg) BP for nine months after injection as compared with untreated SHR. Left ventricular (LV) thickness (1.87±0.1 vs 2.16±0.3* mm), LV end-systolic dimensions (3.96±0.3 vs 4.66±0.6* mm) and LV mass (0.4±0.01 vs 0.49±0.01* gr) were reduced, while ejection fraction was increased (83±2 vs 74±4* %) in BNP-treated compared to untreated SHR. Circumferential systolic strain (-5.04±0.4 vs -3.74 ±0.4* %) and strain rate of the early phase of diastole (-4.57±2.1 vs -2.41±1.3 1/s) were improved in BNP-treated compared with controls. Importantly, the improvement in cardiac function and structure also resulted in a significant increase in survival (p<0.001 vs untreated SHR). Non-cardiac overexpression of BNP, via AAV2 vector, was not associated with changes in plasma BNP and BP in SHR. Nevertheless, normotensive Wistar rats injected with AAV9 proBNP vector showed significantly reduced heart/body weights (0.31± 0.1 vs 3.9±0.1* %) four weeks after injection without BP reduction compared to untreated rats.

The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure

ObjectivePro-brain natriuretic peptide (proBNP)-108 and N-terminal proBNP-76 (NT-BNP) contain seven sites for O-linked oligosaccharide attachment. Currently, levels of glycosylated NT-BNP are probably underestimated because it is not recognised by one...

The association of plasma prorenin level with an oxidative stress marker, 8-OHdG, in nondiabetic hemodialysis patients

Circulating prorenin contributes to the pathogenesis of tissue damage leading to cardiovascular disease (CVD) in hypertension and diabetic mellitus (DM) by activating the tissue renin-angiotensin-aldosterone (RAS) system; however, little is known about its roles in hemodialysis (HD) patients. We evaluated plasma prorenin level and prorenin receptor [(P)RR] expression in peripheral blood mononuclear cells (PBMCs) in 49 nondiabetic HD (non-DM-HD) patients. Then we investigated the association between plasma prorenin level or (P)RR expression level in PBMCs and CVD-predictive biomarkers. The plasma prorenin level increased in non-DM-HD patients [147.1±118.9pg/ml (standard value <100pg/ml)]. The (P)RR mRNA expression level in PBMCs also increased 1.41±0.39-fold in non-DM-HD patients compared with that in healthy control subjects (p<0.001). Although plasma prorenin level did not correlate with plasma BNP level and plasma high-sensitivity C-reactive protein level, it significantly correlated with plasma 8-hydroxydeoxyguanosine (8-OHdG) level (r=0.535, p<0.001). The plasma prorenin level did not correlate with plasma renin activity (PRA), plasma angiotensin I (AT I) level, plasma angiotensin II (AT II) level and plasma aldosterone (Ald) level. PRA, plasma AT I level, plasma AT II level and plasma Ald level did not correlate with the level of any CVD predictive biomarker. (P)RR expression level in PBMCs did not correlate with the level of any CVD predictive biomarker. The plasma prorenin level and (P)RR expression level in PBMCs increased, and the plasma prorenin level was associated with plasma 8-OHdG level independent of circulating RAS in non-DM-HD patients.

Validez y utilidad del péptido ventricular natriurético tipo B (BNP) en la detección de disfunción ventricular izquierda en pacientes de alto riesgo en atención primaria

Objective The aim of this study was to determine the accuracy of BNP test for early diagnosis of left ventricular dysfunction in patients at high-risk for heart failure. Design Cross-sectional descriptive study. Setting 7 Primary Care Centres in Madrid (Spain). Participants A consecutive sample of 204 consecutive asymptomatic patients with high risk for heart failure (Stages A-B, AHA/ACC Classification). Main measurements BNP plasma levels were measured in the clinical setting using Triage BNP Test ® (Biosite ®) and an echocardiography was performed in the following 3 days in a single hospital unit as a reference standard. Plasma BNP levels were compared depending on the presence/absence of left ventricular dysfunction (LVD), type and severity degree. Sensitivity, specificity, positive and negative predictive values, and Área under the receiver operating characteristic curve (ROC) for BNP assay were calculated. Results BNP values were significantly higher ( P<.001) in patients with left ventricular systolic dysfunction (LVSD). No significant differences were found for diastolic dysfunction. The best cut-off value to discriminate the patients with LVSD was 71.00 pg/ml, with an Área under the ROC curve of 0.757 (95% CI 0.64-0.87). Sensitivity for LVD diagnosis was 75% (95% CI 50.66-99.34), specificity 70.19% (95% CI 62.81-77.57), positive predictive value (PPV) 20% (95% CI 9.05-30.95), and negative predictive value (NPV) 96.58% (95% CI 92.86-100), with LVSD prevalence of 9.04% in this population. Conclusions BNP determinations are of value in diagnosing LVSD in a primary care setting, with similar sensitivities and specificities. Due to the high NPV is useful to rule-out patients for echocardiography.

Clinical and Echocardiographic Correlates of Plasma B-type Natriuretic Peptide Levels in Patients with Aortic Valve Stenosis and Normal Left Ventricular Ejection Fraction

Several studies suggest that BNP testing may help define the timing of aortic valve surgery in patients with aortic valve stenosis (AVS) prior onset of overt LV systolic dysfunction. The aim of this study was to identify clinical and echocardiographic correlates of plasma BNP levels in a large cohort of patients with AVS and preserved LV ejection fraction. One hundred thirty-five consecutive patients were prospectively included in the present study (Mean age 73 ± 13 years old, 66 (49%) male). Eighty-nine patients (66%) had severe AVS (aortic valve area <0.6 cm(2) /m(2) BSA). Plasma BNP levels, clinical and comprehensive Doppler echocardiography evaluation was performed in all patients. Independent clinical correlates of plasma BNP levels (R(2) = 0.19) were older age (P < 0.0001) and presence of AVS symptoms (P = 0.004). Independent echocardiographic correlates of plasma BNP levels (R(2) = 0.38) were E/Ea ratio (P = 0.01), LV mass index (P = 0.018), left atrial surface (P < 0.0001) and systolic pulmonary artery pressure (sPAP; P = 0.004). Overall, independent correlates of plasma BNP levels (R(2) = 0.47) were older age (P = 0.001), known coronary artery disease (P = 0.047), increased LV mass index (P = 0.001), left atrial enlargement (P = 0.002), and increased sPAP (P = 0.003). In patients with AVS and normal LV ejection fraction, plasma BNP predominantly reflects the clinical and echocardiographic consequences of afterload burden imposed on the left ventricle rather than the severity of valve stenosis, per se.

A synthetic prostacyclin agonist, ONO-1301, ameliorates ventricular remodeling after acute myocardial infarction via upregulation of HGF in rat

It has been shown that administration of angiogenic factors can augment collateral growth in ischemic tissues. We previously reported that ONO-1301, a synthetic prostacyclin agonist with thromboxane-synthase inhibitory activity, promotes production of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) from various cell types. We evaluated therapeutic efficacy of ONO-1301 in rat cardiac ischemia model. Ligation of left anterior descending coronary arteries was performed to 10-week-old Wistar rats, and the slow releasing form of ONO-1301 was administrated subcutaneously 3 days after the ligation (control group and ONO-1301 group). Hemodynamic parameters and plasma BNP levels were significantly improved by ONO-1301. Histological analysis revealed that ONO-1301 suppressed fibrotic changes in the myocardium (27.7±3.1% vs 23.3±3.6%, p<0.01). HGF and c-Met expression in the myocardium was significantly up-regulated by ONO-1301. Beneficial effects of ONO-1301 were abrogated by administration of a neutralizing anti-HGF antibody. These findings indicate that ONO-1301 has cardioprotective effects in the rat ischemic heart model via augmentation of endogenous HGF production.

AS-258 Performance of B Type Natriuretic Peptide in the Early Diagnosis of Left Ventricular Diastolic Dysfunction in High Risk Subjects

Plasma BNP, a noble biomarker, increases proportionately with increasing left ventricular pressure. It is well documented that plasma BNP increases in left ventricular systolic dysfunction. Our study is to evaluate the role of plasma BNP level in early diagnosis of left ventricular diastolic dysfunction in patients with risk factors like hypertension, diabetes, dyslipidemia, ischemic heart disease.

The clinical significance of the change of plasma BNP levels in patients with grades sepsis

Objective To study the clinical significance of the change of plasma BNP levels in patients with grades sepsis and its correlation with the left ventricular ejection fraction.Methods One hundred patients of sepsis who were admitted in intensive care unit of Taizhou hospital were selected.It was divided into four groups:30 patients with septic shock,40 patients with severe sepsis,30 patients with sepsis and 20 persons without disease as control group.The concentration of plasma BNP was determined using sandwich immunoflurescence,and ultrasonic cardiogram was used to evaluate heart function and clinical features in all groups.To compare with the differences of the concentration of plasma BNP and the correlation between the concentration of Plasma BNP and LVEF in all groups,the data of clinical features,28-day mortality,prognostic values of BNP and the length of stay (ROG) in ICU were collected and compared.Result Plasma BNP levels in patients with septic shock[ (976.3 ± 160.7) pg/ml] were obvious higher than severe sepsis[ (648.4 ± 267.3) pg/ml ],sepsis [ (217.2 ± 89.7) pg/ml ] and control group [ (50.3 ± 25.4)pg/ml] (P ＜0.01).LVEF in patients with septic shock [ (48.2 ±9.6)% ] was obvious lower than severe sepsis[ (52.8 ±9.4)% ],sepsis[ (61.3 ± 8.9)% ] and control group[ (66.4 ±9.3)% ] (P ＜0.05 or P ＜0.01).It appeared to be inverse relationship between LVEF and the plasma BNP levels (r =-0.876,-0.724,P ＜0.01).BNP levels were significantly higher in non-survivors compared with survivors[ (1367.6±506.4)pg/ml vs (420.3 ±82.6)pg/ml,P ＜0.01 ].The receiver operating characteristic (ROG) curves indicated that values of areas under the curve of plasma BNP levels for 28-days mortality were 0.918(P ＜0.01).Conclusion The concentration of plasma BNP in patients was different in different grades of sepsis.It appeared to be negative correlation between the concentration of plasma BNP and LVEF.Plasma BNP levels had predictive value to the patients with sepsis. Key words: Sepsis/BL; Natriuretic peptide,brain/BL; Stroke volume

Atrial Fibrillation Was Associated with Sleep-Disordered Breathing in Heart Failure Patients

Background: Sleep-disordered breathing (SDB) is frequently observed in heart failure patients. Central sleep apnea and Cheyne-Stokes respiration (CSR) have been reported predictors of mortality in systolic heart failure patients. However, little is known about association between atrial fibrillation and SDB in heart failure patients among Japanese population. Methods: Consecutive patients (n=45) with congestive heart failure admitted to our hospital between June 2009 and August 2010 were enrolled. SDB examination was performed using portable monitoring and polysomnography immediately before discharge after stabilizing heart failure by optimal pharmacological therapy. Those patients were classified into two groups according to apnea hypopnea index (AHI): L group (AHI 15). Clinical characteristics were compared between the groups. Results: Twenty-three (51%) patients were classified into L group (AHI=6.9±4.6) and 22 (49%) patients into H group (AHI=33.0±12.6). There was no significant difference in age, body mass index, medication (β-blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, spironolactone), cardiac function and eGFR between the groups. Prevalence of atrial fibrillation (33% vs. 16%, p=0.025) and CSR (47% vs. 2%, p<0.001) and plasma BNP level (480±443 pg/ml vs. 246±262 pg/ml, p=0.035) were significantly higher in H than in L group. Conclusions: Japanese heart failure patients with SDB had higher prevalence of atrial fibrillation and CSR and higher plasma BNP level compared with the patients without SDB.

Noncontact Mapping-Guided Sinus Node Modification for Inappropriate Sinus Tachycardia

Case 1, 46-year-old female suffered from palpitation and diagnosed as inappropriate sinus tachycardia (IST). Her total heart beats in Holter ECG revealed 12445 beats/day despite taking verapamil and metprolol. We performed EnSite multielectrode array-guided electrophysiological study and radiofrequency catheter ablation (RFCA). Baseline heart rate (HR) was 90 bpm. HR increased to 140 bpm and earliest activation site (EAS) shifted cranially about 25 mm by isoproterenol (ISO) infusion. RFCA to EAS was repeated until 15% decrease of HR was achieved from the baseline. At 3 months after RFCA, she spent comfortably and her HR was 70 bpm without any medication. Case 2, 55-year-old female with dyspnea and pretibial edema showed total heart beats of 145533 beats/day with taking verapamil and carvedilol. Her LVEF was 31% and plasma BNP level was 215 pg/ml. Baseline HR was 130 bpm and HR increased to 140 bpm by ISO infusion. EAS was at posterior side of mid-crista terminalis. After an RFCA at this site, EAS shifted cranially to RA-SVC border, and HR increased to 150 bpm. By repeated RFCA to EAS, 30% decrease of HR was achieved from the baseline, and EAS shifted caudally about 26 mm. At 6 months after RFCA, LVEF improved to 45% and plasma BNP level improved to 34 pg/ml. Conclusions: Though clinical manifestations and responses to ISO were variable, noncontact mapping-guided sinus modification may be an effective method to control IST.

Usefulness of SafeR Mode for Reduction of Ventricular Pacing in Patients with Sick Sinus Syndrome

Background: It was reported that unnecessary right ventricular pacing increased the risk of atrial fibrillation (Af) or congestive heart failure (CHF). We evaluated the usefulness of SafeR mode, a new pacing algorithm designed to minimize ventricular pacing. Methods: 18 patients (75±8 years old, 7 men) who had pacemaker implantation were randomized to SafeR mode or DDD mode for 3 months and then crossed over to the alternate pacing modality for 3 months. Atrioventricular (AV) conduction interval during atrial pacing set at 90 beats/min was measured and the paced/sensed AV delays were programmed at 30 msec longer than the measured AV interval in device implantation. On completion of the 3-month crossover phase, we evaluated the percentage of ventricular pacing, the number of premature atrial conduction (PAC), premature ventricular conduction (PVC), plasma BNP level and the prevalence of Af. Results: The percentage of ventricular pacing was significantly lower in SafeR mode than that in DDD mode (3.3% vs 31.1%, P<0.001). The number of PAC, PVC, BNP and Af episodes tend to be reduced by SafeR mode compared with DDD mode, however, there were no statistically difference in both modes. Adverse events potentially related with SafeR mode were not observed. Conclusion: SafeR mode significantly reduced unnecessary right ventricular pacing. This mode may reduce the risk of Af or CHF in patient with SSS.

Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction

Aims. Galectin-3 is an emerging biomarker which has been studied in relatively small heart failure (HF) cohorts with predominantly systolic HF. We studied the prognostic value of base-line galectin-3 in a large HF cohort, with preserved and reduced left ventricular ejection fraction (LVEF), and compared this to other biomarkers.Methods. We studied 592 HF patients who had been hospitalized for HF and were followed for 18 months. The primary end-point was a composite of all-cause mortality and HF hospitalization.Results. A doubling of galectin-3 levels was associated with a hazard ratio (HR) of 1.97 (1.62–2.42) for the primary outcome (P < 0.001). After correction for age, gender, BNP, eGFR, and diabetes the HR was 1.38 (1.07–1.78; P = 0.015). Galectin-3 levels were correlated with higher IL-6 and CRP levels (P < 0.002). Changes of galectin-3 levels after 6 months did not add prognostic information to the base-line value (n = 291); however, combining plasma galectin-3 and BNP levels increased prognostic value over either biomarker alone (ROC analysis, P < 0.05). The predictive value of galectin-3 was stronger in patients with preserved LVEF (n = 114) compared to patients with reduced LVEF (P < 0.001).Conclusions. Galectin-3 is an independent marker for outcome in HF and appears to be particularly useful in HF patients with preserved LVEF.

BNP as marker of heart dysfunction in patients with liver cirrhosis

Patients with liver cirrhosis suffer various degrees of cardiac dysfunction which may be crucial in determining the outcome of surgery. The aim of this study was to determine the role of natriuretic peptides on the assessment of cardiac dysfunction in patients with liver cirrhosis. Prospective longitudinal study of 30 patients with hepatic cirrhosis. Severity of disease was assessed according to the Child-Turcotte-Pugh and Model for End Stage Liver Disease (MELD) scores. Cardiac function was assessed using endocrine markers [atrial natriuretic peptide-brain natriuretic peptide (BNP)] and isotopic ventriculography at baseline and after stimulation with dobutamine. The ejection fraction was higher in patients with Child A+B and MELD less than 18 than in patients with advanced liver disease. A significant correlation between BNP plasma levels and MELD values was observed. Dobutamine induced a marked improvement in myocardial performance associated to a decrease in BNP levels. Multivariate analysis showed that BNP has prognostic value as a marker of cardiac ejection fraction. Patients whose baseline BNP concentrations were more than 70 pg/ml had an ejection fraction of around 45%. This study has shown that increased baseline BNP concentrations may be regarded together with high Child and MELD scores, as the critical cardiac dysfunction threshold in cirrhotic patients.

Does the Wall Stress Alone Stimulate the Natriuretic Peptide System?

HomeHypertensionVol. 56, No. 6Does the Wall Stress Alone Stimulate the Natriuretic Peptide System? Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBDoes the Wall Stress Alone Stimulate the Natriuretic Peptide System? Olli Arjamaa and Mikko Nikinmaa Olli ArjamaaOlli Arjamaa Center of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, Turku, Finland Search for more papers by this author and Mikko NikinmaaMikko Nikinmaa Center of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, Turku, Finland Search for more papers by this author Originally published1 Nov 2010https://doi.org/10.1161/HYPERTENSIONAHA.110.162628Hypertension. 2010;56:e175Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: November 1, 2010: Previous Version 1 To the Editor:We read with great interest the article by Maeder et al1 published recently in Hypertension. We comment on this article by presenting some additional facts from the published literature, which may help in bringing about a new interpretation of the enormous amount of published clinical results on natriuretic peptides and open a new avenue of research. By the end of August 2010, a PubMed search produced >24 000 hits with “natriuretic peptide.” The high number of articles would suggest that there exist conflicting and confusing conclusions as to the role of natriuretic peptides in cardiology.The concept that cardiac wall stress is the primary stimulus for the release of atrial natriuretic peptide (ANP; and also brain natriuretic peptide [BNP]) originates from the article by Lang et al2 in which a large and rapid intravascular volume load, produced experimentally, resulted in increased plasma levels of ANP in the laboratory rat, a species from dry and warm environments hardly ever experiencing such intravascular volume changes. The massive diuresis and natriuresis seen in rat after infusion of atrial extracts led to the conclusion that natriuretic peptides are hormones primarily regulating blood pressure. A high number of articles followed which verified that increased cardiac distension or pressure leads to increased plasma levels of ANP or BNP in different experimental studies and across a spectrum of cardiac diseases in humans.3Parallel to pressure studies, it was shown by Baertschi et al4 that hypoxia was a direct and sufficient stimulus for the release of ANP from isolated perfused hearts of the rat and rabbit. These findings were corroborated in many studies with isolated cardiac myocytes and with isolated Langendorff-perfused animal hearts in the absence of any change in mechanical load.3 When the blood flow was surgically reduced to the area of the anterior ventricular wall of the heart of pigs resulting in hypoxia, the tissue content of BNP mRNA was increased several fold and, interestingly, hypoxia-response elements have been characterized from the promoter sequence of both the ANP and BNP genes.3It appears that the measurement of natriuretic peptides, especially the BNP, has not met all of the expectations as a simple and useful tool in clinical cardiology. Confusing data have accumulated from the studies with critically ill patients in intensive care units,5 where patients most likely experience reduced tissue oxygenation.Could it be possible that, in many cardiac diseases, there are hypoxic conditions in the heart tissue that play an independent factor regulating the synthesis of natriuretic peptides, thus confusing the interpretation of wall stress effect? It is noteworthy that, when in experimental animals with right ventricular hypertrophy, hypoxic conditions were replaced by normoxia, the ANP content fell to control levels despite persistent right ventricular hypertrophy.3Sources of FundingThis work was funded by the Academy of Finland.DisclosuresNone.1 Maeder MT, Mariani JA, Kaye DM. Hemodynamic determinants of myocardial B-type natriuretic peptide release: relative contributions of systolic and diastolic wall stress. Hypertension. 2010; 56: 682–689.LinkGoogle Scholar2 Lang RE, Thölken H, Ganten D, Luft FC, Ruskoaho H, Unger T. Atrial natriuretic factor: a circulating hormone stimulated by volume loading. Nature. 1985; 314: 264–266.CrossrefMedlineGoogle Scholar3 Arjamaa O, Nikinmaa M. Natriuretic peptides in hormonal regulation of hypoxia responses [review]. Am J Physiol. 2009; 296: R257–R264.Google Scholar4 Baertschi AJ, Hausmaninger C, Walsh RS, Mentzer RM Jr, Wyatt DA, Pence RA. Hypoxia-induced release of atrial natriuretic factor (ANF) from the isolated rat and rabbit heart. Biochem Biophys Res Commun. 1986; 140: 427–433.CrossrefMedlineGoogle Scholar5 Dixon J, Philips B. Commentary. The interpretation of brain natriuretic peptide in critical care patients: will it ever be useful? Critical Care. 2010; 14: 184–1855.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Rodriguez-Gonzalez M, Perez-Reviriego A, Castellano-Martinez A and Cascales-Poyatos H (2019) N-terminal probrain natriuretic peptide as biomarker for diagnosis of Kawasaki disease, Biomarkers in Medicine, 10.2217/bmm-2018-0324, 13:4, (307-323), Online publication date: 1-Mar-2019. Maeder M and Kaye D (2010) Response to Does the Wall Stress Alone Stimulate the Natriuretic Peptide System?, Hypertension, 56:6, (e176-e176), Online publication date: 1-Dec-2010. December 2010Vol 56, Issue 6 Advertisement Article InformationMetrics https://doi.org/10.1161/HYPERTENSIONAHA.110.162628PMID: 21041701 Originally publishedNovember 1, 2010 PDF download Advertisement SubjectsChronic Ischemic Heart Disease

Letter by Lowenthal et al Regarding Article, “BNP Levels Predict Outcome in Pediatric Heart Failure Patients: Post Hoc Analysis of the Pediatric Carvedilol Trial”

To the Editor: We read with interest the post hoc analysis of plasma BNP levels and outcomes in pediatric heart failure patients from the Pediatric Carvedilol Trial by Auerbach et al.1 We agree that BNP cutoff values obtained from the adult population, mainly with ischemic heart disease, cannot be used in managing children with structurally abnormal hearts and secondary myocardial dysfunction. Extrapolation from the adult population to the diverse congenital heart defect population, ranging …