Brain Natriuretic Peptide Secretion Research Articles

Influence of left atrial expansion and decreased interventricular septal wall motion following a weakened atrial kick on brain natriuretic peptide secretion in early-stage heart failure

Abstract Background The secretion of brain natriuretic peptide (BNP) by left ventricular (LV) myocytes increases even in patients with normal LV function. Currently, the cause of BNP increase in patients with stages A and B chronic heart failure remains unknown. Purpose To investigate the increase of BNP in early-stage, asymptomatic heart failure. Methods Consecutive patients (N=188; mean age: 68±11 years; body mass index: 23.0±3.9 kg/m2, female/male: 88/100) with heart failure (stages A and B), including non-valvular atrial fibrillation (NVAF), and LV ejection fraction >50% with estimated glomerular filtration rate >30% were recruited in this study. The echocardiographic parameters of LV systolic function (e.g., LV endo-diastolic/endo-systolic volume and ejection fraction) or diastolic markers (e.g., E/A ratio calculated from the trans mitral flow velocity and E/e' ratio), in addition to the data obtained from tissue Doppler images, were evaluated. LA volume was obtained from a three-dimensional heart model. Moreover, LV and left atrial (LA) global longitudinal strains were evaluated. The BNP levels measured within 1 month from echocardiographic examination were compared with the echocardiographic markers, in addition to an estimated glomerular filtration rate. Results BNP was elevated in patients with NVAF (NVAF, median: 63.0 pg/ml [quartile: 33.2–74.7 pg/ml]; non-NVAF, median: 25.6 pg/ml [quartile: 13.5–50.8 pg/ml]; p=0.0015) and patients with stage B heart failure (stage B, median: 41.7 pg/ml [quartile: 21.5–67.5 pg/ml]; stage A, median: 23.4 pg/ml [quartile: 11.7–39.0 pg/ml]; p=2.99E-05). The presence of hypertension and the sex of patients did not lead to significant differences in this population. The LA volume corrected by the body surface area was well correlated with the BNP value (r=0.55; 95% confidence interval [CI]: 0.44–0.64; p=4.42E-16) and age (r=0.51; 95% CI: 0.40–0.61; p=4.64E-14). LA global longitudinal strain (r=−0.42; 95% CI: −0.53 to −0.29; p=3.05E-09) and the velocity of interventricular septum during atrial contraction (r=−0.40; 95% CI: −0.51 to −0.27; p=1.84E-08) were also correlated with BNP elevation. However, the markers of diastolic and systolic function of LV were not correlated with BNP increase in patients with subclinical heart failure. Multivariate analysis revealed that LA volume (β: 0.991; 95% CI: 0.682–1.299; p=1.85E-09), stage B heart failure (β: 0.116; 95% CI: 0.016–0.216; p=0.023), age (β: 0.013; 95% CI: 0.008–0.018; p=6.414E-07), body mass index (β: −0.020; 95% CI: −0.033 to 0.007; p=0.002), and a decrease in the velocity of interventricular septum during atrial contraction (β: −0.048; 95% CI: −0.070 to −0.026; p=2.683E-05) contributed to the increase in BNP. Conclusion LA enlargement with no relation to diastolic function, age, and diminishment of interventricular motion caused by atrial contraction may be sensitive markers of BNP secretion in patients with subclinical stage, asymptomatic heart failure. Funding Acknowledgement Type of funding sources: None.

NT-pro brain natriuretic peptide in patients with type 2 diabetes mellitus without overt heart failure: a hospital based cross sectional study

Background: Increased secretion of brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) occurs mainly with increased tension in the ventricular walls, decreased oxygen supply, acute myocardial infarction, chronic cardiac heart failure, and in hypertrophy of the heart. Objective was to find out the prevalence and profile of NT-pro BNP levels in patients with type 2 diabetes mellitus (DM) without overt heart failure.Methods: Hospital based cross sectional observational study was conducted in the Department of Medicine, Pt. JNM Medical College and associated Dr. BRAM Hospital Raipur, Chhattisgarh involving 106 patients of type 2 DM during the period of April 2019 to April 2020, after ethical approval from institutional ethical committee.Results: The levels of NT pro BNP was found to be elevated in 87.7% patients of DM type 2. Majority of them were from 51-60 years age group (35.5%). Elevated NT proBNP levels was seen in 23.58% of patients having grade I diastolic dysfunction, 3.7% patients with grade II diastolic dysfunction and 1.88% patients having grade III diastolic dysfunction on echocardiography out of the 106 patients. Regardless of presence of diastolic dysfunction on echo, 93 (87.73%) patients out of the total study group of 106 patients had elevated BNP suggesting cardiac dysfunction. In the present study, 30.19% patients with diabetes were found to have varying degrees of diastolic dysfunction on echocardiography.Conclusions: The prevalence of elevated NT pro BNP was 87.7%. Commonly observed age group with elevated NT pro BNP was 51-60 years. NT pro BNP was elevated in 88.7% of males and in 88.36% of females. Prevalence of elevated NT pro BNP was higher in grade 1 diastolic dysfunction with DM duration of more than 5 years (33.3%). Higher prevalence of elevated NT pro BNP was seen in grade I diastolic dysfunction (23.58%).

Reactivation of fatty acid oxidation by medium chain fatty acid prevents myocyte hypertrophy in H9c2 cell line.

Metabolic shift is an important contributory factor for progression of hypertension-induced left ventricular hypertrophy into cardiac failure. Under hypertrophic conditions, heart switches its substrate preference from fatty acid to glucose. Prolonged dependence on glucose for energy production has adverse cardiovascular consequences. It was reported earlier that reactivation of fatty acid metabolism with medium chain triglycerides ameliorated cardiac hypertrophy, oxidative stress and energy level in spontaneously hypertensive rat. However, the molecular mechanism mediating the beneficial effect of medium chain triglycerides remained elusive. It was hypothesized that reduction of cardiomyocyte hypertrophy by medium chain fatty acid (MCFA) is mediated by modulation of signaling pathways over expressed in cardiac hypertrophy. The protective effect of medium chain fatty acid (MCFA) was evaluated in cellular model of myocyte hypertrophy. H9c2 cells were stimulated with Arginine vasopressin (AVP) for the induction of hypertrophy. Cell volume and secretion of brain natriuretic peptide (BNP) were used for assessment of cardiomyocyte hypertrophy. Cells were pretreated with MCFA (Caprylic acid) and metabolic modulation was assessed from the expression of medium-chain acyl-CoA dehydrogenase (MCAD), cluster of differentiation-36 (CD36) and peroxisome proliferator-activated receptor (PPAR)-α mRNA. The signaling molecules modified by MCFA was evaluated from protein expression of mitogen activated protein kinases (MAPK: ERK1/2, p38 and JNK) and Calcineurin A. Pretreatment with MCFA stimulated fatty acid metabolism in hypertrophic H9c2, with concomitant reduction of cell volume and BNP secretion. MCFA reduced activated ERK1/2, JNK and calicineurin A expression mediated by AVP. In conclusion, the beneficial effect of MCFA is possibly mediated by stimulation of fatty acid metabolism and modulation of MAPK and Calcineurin A.

Influence of thyroid dysfunction on brain natriuretic peptide level in health examination participants.

The tissue-specific circulating markers of thyroid hormone action on cardiac function have not been established. Although the relationship between thyroid function and plasma brain natriuretic peptide (BNP) levels has been evaluated in patients with thyroid disorders, the relationship between these parameters in the general population has not been yet studied. We conducted retrospective cohort study by health examination with concurrent measurements of TSH, free T4, body mass index, systolic blood pressure, hemoglobin, and estimated glomerular filtration rate from participants who visited the Department of Health Checkup, Enshu Hospital between July 2008 and March 2017. After participants with abnormal electrocardiogram and/or any history of cardiac disease were excluded, 2,807 individuals were subjected. Multivariate analyses demonstrated that, when compared to euthyroidism (n = 2,629), the increase in BNP levels was significant in overt thyrotoxicosis (n = 21) but not in subclinical thyrotoxicosis (n = 53) or subclinical hypothyroidism (n = 97). Interestingly, the standardized partial regression coefficient was the smallest for thyroid function category (overt thyrotoxicosis compared to euthyroidisim; β = 0.048, p = 0.006) among the independent variables including age, body mass index, systolic blood pressure, and hemoglobin. In longitudinal comparison, we identified 986 participants who had sequential data on the measurements and were stable as euthyroidism and subclinical hypothyroidism. Their annual percent change in BNP demonstrated no significant differences. In conclusion, a direct stimulatory effect of thyroid hormone on the secretion (or production) of BNP was confirmed even in a large number of health examination participants.

BNP as a Major Player in the Heart-Kidney Connection

Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypertension and cardiac hypertrophy. Although it is known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease, the mechanism remains unknown. Here, we review the functions and the roles of BNP in the heart-kidney interaction. In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS). The renal medulla has been reported to express depressor substances. The extract of the papillary tips from kidneys may induce the expression and secretion of BNP from cardiomyocytes. A better understanding of these processes will help accelerate pharmacological treatments for heart-kidney disease.

Renal papillary tip extract stimulates BNP production and excretion from cardiomyocytes.

BackgroundBrain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases, including heart failure, hypertension and cardiac hypertrophy. It is also known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease; however, the mechanism remains unclear.Methods and resultsWe developed a BNP reporter mouse and occasionally found that this promoter was activated specifically in the papillary tip of the kidneys, and its activation was not accompanied by BNP mRNA expression. No evidence was found to support the existence of BNP isoforms or other nucleotide expression apart from BNP and tdTomato. The pBNP-tdTomato-positive cells were interstitial cells and were not proliferative. Unexpectedly, both the expression and secretion of BNP increased in primary cultured neonatal cardiomyocytes after their treatment with an extract of the renal papillary tip. Intraperitoneal injection of the extract of the papillary tips reduced blood pressure from 210 mmHg to 165 mmHg, the decrease being accompanied by an increase in serum BNP and urinary cGMP production in stroke-prone spontaneously hypertensive (SHR-SP) rats. Furthermore the induction of BNP by the papillary extract from rats with heart failure due to myocardial infarction was increased in cardiomyocytes.ConclusionsThese results suggested that the papillary tip express a substance that can stimulate BNP production and secretion from cardiomyocytes.

Novel function of α1D L-type calcium channel in the atria

Ca entry through atrial L-type Calcium channels (α1C and α1D) play an important role in muscular contraction, regulation of gene expression, and release of hormones including atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP). α1D Ca channel is exclusively expressed in atria, and has been shown to play a key role in the pathogenesis of atrial fibrillation. Recent data have shown that the small conductance calcium-activated potassium channel, SK4 is also atrial specific and also contributes prominently to the secretion of ANP and BNP. However, its functional role in the heart is still poorly understood. Here we used α1D gene heterozygous (α1D+/-) mice and HL-1 cells to determine the functional contribution of SK4 channels to α1D–dependent regulation of ANP and BNP secretion in response to endothelin (ET), and/or mechanical stretch. Immunoprecipitation with α1D specific antibody and western blotting with SK4 specific antibody on the immuno-precipitated protein complex showed a band at 50 KDa confirming the presence of SK4 in the complex and provided evidence of interaction between SK4 and α1D channels. Using RT-PCR, we observed a 2.9 fold decrease in expression of Cacna1d (gene encoding α1D) mRNA in atria from α1D+/−mice. The decrease in α1D mRNA corresponded with a 4.2 fold decrease in Kcnn4 (gene encoding SK4) mRNA from α1D+/− mice. These changes were paralleled with a 77% decrease in BNP serum levels from α1D+/− mice. When α1D was knocked down in HL-1cardiomyocytes using CRISPR/Cas9 technology, a 97% decrease in secreted BNP was observed even in cells subjected to stretch and endothelin. In conclusion, our data are first to show that α1D Ca and SK4 channels are coupled in the atria, and that deletion of α1D leads to decreased SK4 mRNA and BNP secretion providing evidence for a novel role of α1D in atrial endocrine function. Elucidating the regulatory factors that underlie the secretory function of atria will identify novel therapeutic targets for treatment and prevention of cardiac arrhythmias such as atrial fibrillation.

Abstract 439: Modeling Diabetic Cardiomyopathy Model Using Human Induced Pluripotent Stem Cell-derived Cardiomyocytes

Background: Diabetic cardiomyopathy (DCM) is one of the major cardiac complications in diabetic patients. However, the underlying mechanisms and pathogenesis of diabetic cardiomyopathy are only partially understood and the specific therapeutic target remains unknown. Here, we developed an in vitro diabetic cardiomyopathy model through simple metabolic manipulation using human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs). Methods: After 30 days from initial differentiation, iPSC-CMs were cultured with maturation medium (containing fatty acid but no glucose) for 3 days to obtain matured cardiomyocyte properties. Maturation extent of iPSC-CMs was analyzed using patch-clamp to analyze electrophysiological properties and RT-PCR to analyze cardiomyocyte-specific structure proteins and ion channel expression. Matured iPSC-CMs were then treated with 11 mM glucose for 2 days. 11 mM glucose represents mild glucose conditions in diabetic patients. Cardiomyopathy phenotype of iPSC-CMs was evaluated by analyzing brain natriuretic peptide (BNP) secretion from iPSC-CMs using ELISA. Result: Differentiated iPSCs-CMs were immature. Following 3 day culture in maturation medium, iPSC-CMs exhibited the cardiomyocyte maturation characteristics: 1) an increase of contractility with diminished automaticity, suggesting progressive maturation toward adult cardiomyocytes, 2) the lower maximal diastolic potential and increased amplitude, indicating functional maturation, and 3) an upregulation of the following gene expression: sarcomeric proteins (e.g., TNNI3, MYL2 and MYL3) and potassium channel α-subunit genes (KCNJ12 and KCNJ4). Matured iPSC-CMs treated with 11 mM glucose showed increase in cell size and BNP secretion (17-fold increase vs. control cells without glucose, p<0.01). These results suggested that cardiomyocytes exposure to the maturation medium followed by diabetic milieu of glucose recapitulate DCM in vitro . Conclusion: We conclude that the phenotype of DCM can be modeled using cultured iPSC-derived cardiomyocytes through diabetic extracellular milieu. This clinically relevant stem cell model would be a powerful platform to study novel mechanisms of DCM and the specific therapeutic targets.

Brain Natriuretic Peptide Levels and Long-Term Outcomes in Acute Decompensated Heart Failure

Background: Brain natriuretic peptide (BNP) is a useful biomarker for managing patients with heart failure. Left ventricular morphology is an important determinant of left ventricular wall stress or BNP secretion, but little data is available regarding the long-term prognostic value of BNP in relation to left ventricular morphology in patients with heart failure. Methods: Plasma BNP levels and left ventricular morphology including end-diastolic/end-systolic volume and mass index on echocardiography were assessed before discharge in 89 consecutive patients hospitalized with acute decompensated heart failure. All patients were prospectively followed for cardiac events defined as cardiac death or rehospitalization due to heart failure. Results: During a follow-up period of up to 10 years, 28 patients died and 24 survived with cardiac events. Levels of BNP in nonsurvivors, survivors with cardiac events, and survivors without cardiac events were as follows: 240 ± 107 pg/ml, 357 ± 71 pg/ml, and 177 ± 23 pg/ml at 1 year after discharge (P = 0.01); 300 ± 63 pg/ml, 307 ± 66 pg/ml, and 157 ± 24 pg/ml at 5 years (P = 0.03); and 357 ± 65 pg/ml, 222 ± 43 pg/ml, and 145 ± 25 pg/ml at 10 years (P <0.01), respectively. Left ventricular morphology did not differ significantly among the 3 groups. Conclusion: Long-term prognosis was associated with BNP levels before discharge, but not with left ventricular morphology, in patients hospitalized with acute decompensated heart failure. The prognostic value of BNP levels on the severity of outcome varied depending on the time after discharge.

Quantitative assay of brain natriuretic peptide in rat cardiomyocytes in the early postreperfusion period

We studied the intensities of accumulation and secretion of brain natriuretic peptide (BNP) in the early postreperfusion period, i.e., 5 min and 1 h after the start of reperfusion in the myocardium of the right atrium of rats. Total ischemia was modeled using Korpachev’s method. Immunocytochemical detection of peptide distribution in secretory cardiomyocytes was performed in ultrathin sections using polyclonal antibodies to BNP. The immunoreactive granules of A and B types were counted in optical fields of 38 × 38 µm2 using a transmission electron microscope. Five minutes after the start of reperfusion, the number of BNPcontaining secretory granules was similar to that observed in the control animals. After a 1-h postreperfusion period, we observed active formation and release of BNP because the number of granules of A and B-types increased by 134 and 210%, respectively, as compared to the intact group. These data demonstrate the stimulating effects of ischemic and reperfusion factors on the processes of synthesis and secretion of BNP in this period.

Adenotonsillectomy Normalizes Hormones and Urinary Electrolytes in Children With Nocturnal Enuresis and Sleep-Disordered Breathing

To assess (1) plasma levels of antidiuretic hormone (ADH) and brain natriuretic peptide (BNP) and urinary levels of electrolytes in children with sleep disordered breathing (SDB), with or without nocturnal enuresis (NE), and (2) the effect of adenotonsillectomy (T&A) on urinary electrolytes and the secretion of ADH and BNP in children with NE and SDB. We previously reported post-T&A improvements in plasma levels of BNP and ADH in children with SDB and NE. However, the differences in plasma concentration of these hormones in SDB children with and without NE, and their relationships with urinary electrolytes, have not yet been addressed. This prospective study compared concentrations of urinary electrolytes and plasma ADH and BNP in (1) children with SDB and NE (study group) and an age- and sex-matched control group of children with SDB without NE, and (2) the study group before and 1-month after T&A. Compared with the control group (n = 31), the study group (n = 37) exhibited significantly lower ADH (P = .04) and higher BNP (P = .009) plasma levels. The differences in urinary electrolytes were not significant. Post-T&A, the study group showed significantly decreased BNP (P = .018), urinary sodium-to-creatinine ratio (P = .02), and urinary calcium-to-creatinine ratio (P = .007) compared with the pre-T&A values. Post-T&A changes in urinary calcium were significantly correlated with changes in sodium excretion (P = .002) and in plasma levels of BNP (P <.001). The presence of NE is associated with altered ADH and BNP levels in children with SDB. T&A led to normalization of ADH and BNP, probably through a calcium- and sodium-dependent mechanism.

Editorial Comment

Nocturia is one of the most bothersome lower urinary tract symptoms. In many ways, nocturia can be considered a “geriatric syndrome.” 1 Inouye S.K. Studenski S. Tinetti M.E. Kuchel G.A. Geriatric syndromes: clinical, research and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007; 55: 780-791 Crossref PubMed Scopus (1112) Google Scholar The condition is highly prevalent among older adults, is generally considered to be multifactorial, and leads to negative clinical outcomes. In some patients, it develops in part because of accumulated effects of decreased function in multiple organ systems. In addition, a number of clinical conditions outside the genitourinary system are also commonly associated with nocturia including congestive heart failure, electrolyte imbalances, diabetes insipidus, and pulmonary and peripheral edema. Certain medications including calcium channel blockers, angiotensin-converting enzyme inhibitors, and diuretics can be associated with nocturia, particularly if taken in the late afternoon or evening. Use of alcohol or caffeine before bedtime can also increase the risk for nocturia. Nocturnal polyuria can also lead to nocturia because of the increased volume of urine production at night. The Impact of Obstructive Sleep Apnea Syndrome on Nocturnal Urine Production in Older Men With NocturiaUrologyVol. 84Issue 4PreviewTo investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria. Full-Text PDF ReplyUrologyVol. 84Issue 4PreviewAs the editorial comment emphasizes the importance of understanding the multiple etiologies of nocturia, various physical conditions and comorbidity diseases involve nocturia mutually in older men. Nocturnal polyuria (NP) is a condition that is most frequently encountered in routine clinical practice. For instance, fluid accumulation in the lower extremities forming leg edema is considered to be not only a source of NP, but also a cause of obstructive sleep apnea syndrome (OSAS). We intended to clarify the effect of OSAS on NP in older male patients with nocturia. Full-Text PDF

The Impact of Obstructive Sleep Apnea Syndrome on Nocturnal Urine Production in Older Men With Nocturia

To investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria. One hundred six men with nocturia aged ≥ 60 years underwent full-night polysomnography to determine whether they had OSAS. Blood count, standard chemistry panel, BNP, urinary ADH, urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 AM, and a frequency volume chart was recorded on the same day that polysomnography was performed. We evaluated 83 patients after excluding 18 with mild OSAS and 5 with nocturnal polyuria index <0.35. Participants with OSAS had higher apnea-hypopnea index (P < .0001) than those without OSAS. Body mass index and systolic blood pressure were higher in OSAS patients than those in the control group. BNP was higher in the OSAS patients than in the control patients (48.6 ± 41.4 vs 30.7 ± 31.5; P = .0006). On urinalysis, OSAS patients showed higher urinary sodium and u-Cre secretion than controls (24.7 ± 11.3 vs 16.2 ± 5.1; P <.0001). Urine osmolarity was also higher in OSAS patients than in the control patients (616 ± 172 vs 516 ± 174; P = .0285). There was no significant difference in urinary ADH and u-Cre (6.7 ± 10.4 vs 6.8 ± 7.8; P = .3617) between the 2 groups. Our results indicated that older men with nocturnal polyuria and OSAS did not compensate their fluid imbalance presented with decreased secretion of ADH but increased BNP level.

The heart as an endocrine organ

The concept of the heart as an endocrine organ arises from the observation that the atrial cardiomyocytes in the mammalian heart display a phenotype that is partly that of endocrine cells. Investigations carried out between 1971 and 1983 characterised, by virtue of its natriuretic properties, a polypeptide referred to atrial natriuretic factor (ANF). Another polypeptide isolated from brain in 1988, brain natriuretic peptide (BNP), was subsequently characterised as a second hormone produced by the mammalian heart atria. These peptides were associated with the maintenance of extracellular fluid volume and blood pressure. Later work demonstrated a plethora of other properties for ANF and BNP, now designated cardiac natriuretic peptides (cNPs). In addition to the cNPs, other polypeptide hormones are expressed in the heart that likely act upon the myocardium in a paracrine or autocrine fashion. These include the C-type natriuretic peptide, adrenomedullin, proadrenomedullin N-terminal peptide and endothelin-1. Expression and secretion of ANF and BNP are increased in various cardiovascular pathologies and their levels in blood are used in the diagnosis and prognosis of cardiovascular disease. In addition, therapeutic uses for these peptides or related substances have been found. In all, the discovery of the endocrine heart provided a shift from the classical functional paradigm of the heart that regarded this organ solely as a blood pump to one that regards this organ as self-regulating its workload humorally and that also influences the function of several other organs that control cardiovascular function.

Can brain natriuretic peptide predict the outcome in patients with acute pulmonary embolism?

Risk of death is high in patients with pulmonary embolism (PE) because of right ventricular (RV) failure. Plasma levels of brain natriuretic peptide (BNP) are increased in cases of isolated chronic right ventricular dysfunction (RVD) and chronic pulmonary hypertension. However, little is known about BNP secretion during acute RVD caused by acute PE.The aim of this study is to determine BNP levels in patients with acute PE with and without RVD and to assess its role in prediction of severity and outcome of these patients. Patients and methodsThis study was conducted on 47 patients with confirmed acute PE who were admitted to the intensive care unit (ICU) of Chest Department, Zagazig University Hospitals. Patients enrolled in this study were subjected to: (a) Transthoracic echocardiography, (b) Measurement of BNP plasma levels, (c) Measurement of D-dimer serum levels and d) Computed tomography pulmonary angiography (CTPA). ResultsThere was statistically highly significant increase in plasma level of BNP (pg/mL) in patients with RVD than those without it. There were highly significant positive correlations between plasma level of BNP (pg/mL) and both RV diameter (mm) and RVSP (mmHg). A plasma BNP level >72.5pg/mL can predict occurrence of RVD, while a plasma level of BNP >150pg/mL can predict death in patients with acute PE. ConclusionAn elevated plasma level of BNP is a prognostic factor for short-term mortality and overall short-term complicated clinical outcome, and it is a powerful indicator of RVD in patients with acute PE in the absence of left ventricular dysfunction (LVD).

FUNCTIONAL EXPRESSION OF TSH RECEPTOR IN THE VENTRICLE OF RATS AND MICE: INVOLVEMENT A REGULATION OF HMGCR BY TSH VIA THE CAMP/PKA/PCREB SIGNALLING PATHWAY

ObjectivesElevated thyroid-stimulating hormone (TSH) and hypercholesterolemia commonly coexist, as typically seen in subclinical hypothyroid, which can lead to and aggravate heart disease if it gets serious. However, there is no...

Plasma Brain Natriuretic Peptide Concentrations in Children with Epilepsy: the Effect of Antiepileptic Drugs

Background and aims: Plasma Brain Natriuretic Peptide (BNP) is recognized as a reliable marker for cardiac dysfunction. Recent studies postulate that intracerebral epileptic activity may trigger BNP secretion by heart or by brain. This prospective study aimed to evaluate BNP concentrations, before and after valproate sodium (VPA) or ox-carbamazepine (OX-CMZ) monotherapy, in children with idiopathic epilepsy.Methods: BNP levels were determined in 59 (aged 4 to 15years, 29 boys) epileptic, otherwise healthy, children and 143 controls (matched for sex and age). BNP fragment was investigated in a fasting blood sample by enzyme immunoassay. In epileptic group the investigations performed before and at 8 and 20 months of VPA (n=27) or OX-CMZ (n=32) monotherapy. Children were at least 48 hours seizure-free. P< 0.05 was considered significant.Results: Epileptic group had significantly lower BNP levels than controls before (p=0.0003) and at 8 months (p=0.0001), but similar levels after 20 months therapy (p=0.12). Anticonvulsant use resulted in an increase of BNP only after 20 months therapy (p=0.0002). There were no significant differences at baseline, 8 and 20 months levels between VPA and OX-CMZ group (p=0.46, p=0.21, p=0.32). BNP levels had no significant correlation with gender (p=0.44), age group (< 6, 6-12, >12years) (p=0.43), BMI (p=0.56) and BMI alterations during therapy (p=0.96) although 67.8% of children increased their body weight at 20 months.Conclusions: Epileptic children have significantly lower BNP concentrations, after a seizure free interval, compared to non-epileptic. The long-term VPA or OX-CMZ monotherapy increase BNP at levels similar to those of healthy children.

Thirty years of research on atrial natriuretic factor: historical background and emerging concepts

The discovery of the natriuretic properties of atrial muscle extracts pointed to the existence of an endocrine function of the heart that is now known to be mediated by the polypeptide hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). On the basis of such a finding, approximately 27 000 publications to date have described a wide variety of biological properties of the heart hormones as well as their application as therapeutic agents and biomarkers of cardiac disease. Stimulation of secretion of ANF and BNP from the atria is mediated through mechanisms involving G proteins of the G(q) or G(o) types. We showed that the latter type underlies the transduction of muscle stretch into stimulated secretion and that it is more highly abundant in atria than in ventricles. The Gα(o)()-1 subunit appears to play a key role in the biogenesis of atrial granules and in the intracellular targeting of their contents. Protein interaction studies using a yeast two-hybrid approach showed interactions between Gα(o)()-1, proANF, and the intermediate conductance, calcium-activated K(+) channel SK4. Pharmacological inhibition of this channel decreases ANF secretion. Unpublished studies using in vitro knockdowns suggest interdependency in granule protein expression levels. These studies suggest previously unknown mechanisms of intracellular targeting and secretion control of the heart hormones that may find an application in the therapeutic manipulation of circulating ANF and BNP.

Brain natriuretic peptide and acute hypobaric hypoxia in humans

In animal models, the secretion of the cardiac hormone, brain natriuretic peptide (BNP), and its closely related peptide, atrial natriuretic peptide (ANP), are stimulated by acute hypoxia. There is extensive human evidence for a rise in ANP under acute hypoxic conditions but very little evidence regarding the BNP response to acute hypoxia in humans. We therefore subjected seven healthy subjects to an acute hypobaric hypoxic stimulus to examine if BNP secretion increases rapidly. Significant hypoxaemia (mean nadir oxygen saturation 62.3%) was induced but no significant rise in BNP occurred. This suggests that either such acute hypoxaemia is well tolerated by the healthy human heart or it is not a stimulus for BNP secretion.

E0653 Level change of plasma BNP and the relationships to the left ventricular aneurysm formation and cardiac performance in patients with acute myocardial infarction

ObjectiveTo investigate the change of brain natriuretic peptide (BNP) in plasma and the relationships with the left ventricular aneurysm (LVA) and cardiac performance in acute myocardial infarction (AMI) patients using...