Brain B-type Natriuretic Peptide Research Articles

B-39 | BNP as a biomarker for pulmonary hypertension in a pediatric population

Amino terminal pro B-type natriuretic peptide (NT-proBNP) and brain B-type natriuretic peptide (BNP) are used as lab markers of cardiac wall tension and early studies indicate that it may be useful as a screening or surveillance test for pediatric pulmonary hypertension. This study is a prospective study of whether the serum level of BNP or NT-pro-BNP was associated with the severity and reactivity of pulmonary hypertension during catheterization of a population of pediatric patients with known or suspected pulmonary hypertension.

A new biomarker of cardiac resynchronization therapy response: cGMP to mature BNP ratio

BackgroundBiomarkers that can predict cardiac resynchronization therapy (CRT) response have not yet been identified. The purpose of this study was to assess whether individual measurements of four brain/B-type natriuretic peptide (BNP) forms, coupled with cyclic guanosine monophosphate (cGMP) might contribute to the prediction of echocardiographic CRT responders. MethodsA BNP precursor (proBNP) and total BNP (= proBNP + mature BNP) were measured with newly developed kits, while an N-terminal fragment of proBNP (NT-proBNP) and cGMP were measured with commercial kits on the day before CRT implantation. Estimated mature BNP (emBNP = total BNP–proBNP), and the ratio of cGMP to each BNP form, as well as the concentrations of three other BNP forms, were prospectively investigated for their capability in predicting a response to CRT. A CRT responder was defined as an improvement in left ventricular ejection fraction >10% and/or a reduction in left ventricular end-systolic volume >15% at 6-month follow-up. ResultsOut of 77 patients, 46 (60%) were categorized as CRT responders. Among the measurement parameters, only the highest quartile of the cGMP to emBNP ratio was an independent predictor of CRT responders (odds ratio 4.87, 95% confidence interval 1.25-18.89, p = 0.02). The cGMP to emBNP ratio was associated with the cumulative events of heart failure hospitalization within one year following CRT implantation (log-rank p = 0.029). ConclusionsThe cGMP to emBNP ratio could be utilized as a predictive biomarker of CRT responders. (Clinical Study on Responder Prediction in Cardiac Resynchronization Therapy Using Individual Molecular Measurement of Natriuretic Peptide: UMIN R000038927).

Telmisartan suppresses cardiac hypertrophy by inhibiting cardiomyocyte apoptosis via the NFAT/ANP/BNP signaling pathway.

Telmisartan, a type of angiotensin II (Ang II) receptor inhibitor, is a common agent used to treat hypertension in the clinic. Hypertension increases cardiac afterload and promotes cardiac hypertrophy. However, the ventricular Ang II receptor may be activated in the absence of hypertension. Therefore, telmisartan may reduce cardiac hypertrophy by indirectly ameliorating hypertensive symptoms and directly inhibiting the cardiac Ang II receptor. Nuclear factor of activated T-cells (NFAT) contributes to cardiac hypertrophy via nuclear translocation, which induces a cascade of atrial natriuretic peptide (ANP) and brain/B-type natriuretic peptide (BNP) expression and cardiomyocyte apoptosis. However, NFAT-mediated inhibition of cardiac hypertrophy by telmisartan remains poorly understood. The present study demonstrated that telmisartan suppressed cardiomyocyte hypertrophy in a mouse model of cardiac afterload and in cultured cardiomyocytes by inhibiting NFAT nuclear translocation, as well as by inhibiting ANP and BNP expression and cardiomyocyte apoptosis, in a dose-dependent manner. The present study provides a novel insight into the potential underlying mechanisms of telmisartan-induced inhibition of cardiomyocyte hypertrophy, which involves inhibition of NFAT activation, nuclear translocation and the ANP/BNP cascade.

ANP-ing Up Diabetes: Impaired Natriuretic Peptide Action in Muscle Forms a Mechanistic Link Between Obesity and Diabetes.

A growing body of work concerns the role of natriuretic peptides (NPs) in metabolism and insulin sensitivity, the latest addition to which is published in this issue of Diabetes (1). Three principal structurally related NPs exist in mammals: atrial natriuretic peptide (ANP), produced primarily by the cardiac atria; brain/B-type natriuretic peptide (BNP), secreted by the ventricle and brain; and C-type natriuretic peptide (CNP), originating from the vascular endothelium, central nervous system, and kidney. They were originally shown to possess potent natriuretic, diuretic, and vasodilatory activity, thus playing a significant role in the prevention of circulatory volume overload and hypertension. These peptides use plasma membrane–situated natriuretic peptide receptors (NPRs) A and B, with the A receptor showing a preference for ANP and BNP and the B receptor being specific for CNP, while a distinct C receptor is responsible for peptide clearance in tissues. Binding of peptides to NPRA leads to the activation of intracellular cyclic guanosine monophosphate (cGMP)-dependent signaling cascades involving cGMP-dependent protein kinases, phosphodiesterases, and ion channels that mediate the physiological effects of NPs (reviewed in ref. 2). Recently, parallel metabolic actions of NPs have been demonstrated in adipose tissue, with selective effects in the visceral adipose depot, expansion of which is most associated with insulin resistance (IR). ANP-stimulated cGMP-mediated phosphorylation of hormone-sensitive lipase results in lipolysis in primates/humans that is independent of β-adrenergic stimulation (3–5), thereby inhibiting visceral adipocyte hypertrophy (6). In addition, ANP treatment causes reduced adipose secretion of proinflammatory cytokines and …

Predictive value of B-type natriuretic peptide for postoperative atrial fibrillation following pulmonary resection for lung cancer

To evaluate the usefulness of atrial natriuretic peptide (ANP) and brain B-type natriuretic peptide (BNP) for predicting postoperative atrial fibrillation (AF), we determined the changes in perioperative ANP and BNP levels in patients undergoing pulmonary resection for lung cancer. This prospective observational study was conducted during the 10-month period from July 2007 to April 2008. Eighty patients with lung cancer underwent lobectomy, segmentectomy or wedge resection. Preoperative evaluations included spirometry and examinations of plasma ANP and BNP-levels, which were also determined on postoperative days 1, 3 and 7. Postoperative AF was identified in 22 (28%) of the patients, and those had significantly higher preoperative ANP and BNP levels as compared with patients without AF. During the postoperative course, patients with postoperative AF also had significantly higher ANP and BNP-levels. The area under the receiver-operating characteristic curve for BNP to predict postoperative AF following pulmonary resection for lung cancer was 0.90 (95% confidence interval (CI), 0.82-0.98; p<0.001). A BNP value of 30pgml(-1) had a sensitivity of 77% and a specificity of 93% for predicting postoperative AF following pulmonary resection for lung cancer. Preoperative BNP level seems to be an appropriate predictor of AF after pulmonary resection.

Prevention Effects of Schisandrin B on Cardiotoxicity Induced by Anthracyclines in Rabbit Model

Background: Dutriomycin, which doxorubicin(DOX) act as a representative among them, has been extensively administrated to treat many kinds of malignant tumours, such as leukemia, lymphoma, breast cancer, and so on. However, its application was confined for its obvious cardiotoxicity in some degree. The mechanism of which cardiotoxicity result from dutriomycin is usually attributed to too much product of free radical. The protective effect of dexrazoxane(DEX) on cardiotoxicity induced by dutriomycin has been proved by animal and clinical researches and its price is relatively expensive. Schisandrin B(SchB), one of the chinese medicine, have showed a significant effect on removing oxygen free radical and hydroxy radical and it has almost no toxicity and adverse reaction. Also, it is easy to procure.Objective: This study is to determine and compare the protective effects of SchB and DEX on the cardiotoxicity of rabbit model induced by doxorubicin.Methods: 46 New Zealand White rabbits were divided into three groups:DOX group(n=14), DOX was administered intravenously with 3mg/kg for each rabbit, once a week;DOX+DEX group(n=17), DOX was also administered intravenously with 3mg/kg for each rabbit, once a week and DEX was given by intra-abdominal cavity with 60mg/kg in 30 minute before the administration of DOX for each rabbit, once a week (week1 'week3) and which was administered intravenously with the same dose by the same way from week 4 to week 12. The total cumulative dose of DEX was 600mg/kg;DOX+SchB group (n=15), DOX was still administered intravenously with 3mg/kg for each rabbit, once a week and SchB was given intravenously with 10.5mg/kg, twice a week.The cumulative dose of SchB was 210mg/kg for each one. The correlated indexes of heart damage induced by DOX and protective action created by DEX and SchB were determined respectively. Quantitative detections of superoxide-dismutase(SOD), malondialdehyde(MDA), cardiac troponin I(cTnI) and brain/B-type natriuretic peptide (BNP) were performed before experiment, at 4 weekend and at 8 weekend after study, as well as at the end of whole research. Echocardiography was performed to evaluate the changes of heart function for each rabbit in three groups before the first administration, at 4 weekend and 8 weekend after study and at the endpoint of the experiment respectively. The rabbits were killed at the endpoint of this study, and the pathological changes of their cardiac tissues were be observed by microscope under the condition of H.E stain and the apoptosis of myocardial cells were detected by TUNEL method.Results: The levels of MDA, cTnI and BNP are increased, and the activity of SOD, left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS) are decreased in the DOX group(P<0.05). Compared with DOX group, the levels of MDA, cTnI and BNP are decreased, and LVEF and LVFS are increased in the DOX+DEX group(P<0.05). The level of MDA is also decreased(P<0.05), and the activity of SOD, LVEF and LVFS are increased(P<0.05) in the DOX + SchB group compared with the DOX group. In the DOX+DEX group, the level of BNP is lower than DOX+SchB group. Compared with the DOX group, the pathological change of myocardium and the apoptotic index of myocardial cells are significantly reduced in the DOX+DEX group and DOX+SchB group.Conclusions: SchB and DEX has both protective effect on cardiotoxicity induced by DOX, and DEX is prior to SchB in the protective effect. The mechanisms of SchB may depends on the effects on scavenging oxygen free radials, decreasing productions of lipid peroxidation, which is different from dexrazoxane.

N-Terminal-ProB-Type Natriuretic Peptide as a Marker for Anthracycline Cardiotoxicity in Children with Acute Lymphoblastic Leukaemia

Background: Anthracyclines (ANTR) are very effective agents in treatment of acute lymphoblastic leukaemia (ALL). However, a potential heart damage caused by ANTR in patients who have been cured of ALL may lessen the success of this cure. Plasma brain B-type natriuretic peptide (BNP) levels are highly sensitive biochemical markers for myocardial damage.Objectives of the study: Our purpose was to evaluate N-terminal proBNP (Nt-proBNP) as a screening test for detecting cardiac dysfunction in children with ALL.Subjects: 156 asymptomatic children (72 girls and 84 boys) who had received ANTR during treatment for ALL were evaluated. They had received ANTR doses of 180 to 480mg/m2 (according to the protocol treatment) at median age of 6.6 years at diagnosis. 47 healthy children constituted the control group.Methods: Concentration of plasma N-terminal proBNP was measured in 420 samples by enzyme immunoassay (Biomedica) before treatment, after 6 months, 2 and 4 years and longer than 5 years after ANTR therapy. 261 echocardiograms (ECHO) were performed in 128 children. Nt-proBNP was measured at the same time. Shortening fraction (%SF) and ejection fraction (%EF) were determined as systolic left ventricular function.Results: Mean Nt-proBNP plasma levels in children with ALL were higher in comparison with the control group (90.7 and 66.2pg/ml respectively) but the difference was not significant (p=0.2). The levels of Nt-proBNP before ALL treatment were significantly the lowest (51.5pg/ml). Later, they were respectively: 108.3pg/ml after 6 months, 97.4pg/ml after 2 years and 92.9pg/ml after 4 years (p=0.0019). The highest levels of NT-proBNP were observed in children with cumulative ANTR doses of 240, 330 and 480mg/m2 (98.8pg/ml, 102.8pg/ml, 86.1pg/ml respectively) (p=0.0008). The lowest levels were observed with the cumulative doses of 180mg/m2 and 300mg/m2 (60.7pg/ml and 58.8pg/ml respectively). The average value of %SF in children with ALL was 39.4% (26 to 52%) and the average value of %EF was 69.95% (51.1 do 83.4%). In children with %SF and %EF lower than the average in both study and control group Nt-proBNP was insignificantly higher than in children whose %SF and %EF were higher than the average in both groups (respectively for %SF: 107.1pg/ml and 97.3pg/ml and for %EF: 106.3pg/ml and 98.8pg/ml).Conclusion: Increased Nt-proBNP levels were observed more often in children who received higher doses of ANTR and in all children after the end of treatment. Independently of ECHO assessment of the left ventricular function, the Nt-proBNP is of value in the detection of subclinical left ventricular dysfunction in children with ALL who were treated with ANTR therapy.