Increase In BNP Research Articles

Phase I study of REGN421 (R)/SAR153192, a fully-human delta-like ligand 4 (Dll4) monoclonal antibody (mAb), in patients with advanced solid tumors.

2502 Background: Dll4, a Notch receptor ligand, may have a role in tumor angiogenesis and is an emerging anticancer target. REGN421 (R) is a fully human IgG1mAb that binds human Dll4 and disrupts Notch-mediated signaling. Methods: Primary objectives of the dose escalation (3+3 design) trial were to determine safety and a recommended phase II dose (RP2D) of R in patients (pts) with advanced cancer. R was given IV at doses of 0.25, 0.5, 1, 2 and 4mg/kg every 3 weeks (Q3W) or 0.75, 1, 1.5, and 3mg/kg every 2 weeks (Q2W). Secondary objectives were PK, immunogenicity, and antitumor activity. Results: 53 pts (M/F=22/31, ECOG 0/1=18/35) were enrolled; 31 pts were treated Q3W at doses of 0.25 - 4 mg/kg; 22 pts were treated Q2W at doses of 0.75 - 3 mg/kg. Two DLTs occurred: Grade 3 (Gr3) nausea (0.5mg/kg Q3W) and Gr3 abdominal pain (1 mg/kg Q2W). A maximum tolerated dose was not reached on either schedule. Grade 3/4 AEs occurred in 29 pts; nausea, abdominal pain, dyspnea, hypoxia, and hypertension (HTN) were reported in ≥ 5%. Most frequent treatment related AEs were fatigue (30%), headache (26%), HTN (26%), and nausea (15%). Six treatment related SAEs (all reversed off treatment) were reported in 4 patients: BNP increase (0.25mg/kg, Gr1), troponin I increase (4mg/kg, Gr3), right ventricular dysfunction (1.5mg/kg, Gr3), left ventricular dysfunction (3mg/kg, Gr3) and 2 events of pulmonary HTN (1.5mg/kg, Gr 3, and 3mg/kg Gr3). Laboratory abnormalities (≥ Gr3) were neutropenia (3) and anemia (2), and elevated ALP (7), ALT (3), bilirubin (3), AST (2), and decreased albumin (1). Anti-tumor activity included 2 PRs (NSCLC BAL-type with a beta-catenin mutation and ovarian cancer [OvCa]), and 16 pts with SD (3 pts had SD > 6 months). Two of 8 pts with OvCa had CA125 responses. R had non-linear target-mediated PK without accumulation. The half-life of R at 3mg/kg Q2W was 7 days. No immunogenicity was observed. Conclusions: REGN421 had an acceptable safety profile, and RP2Ds of 4mg/kg Q3W and 3mg/kg Q2W. Responses and prolonged SD were noted in OvCa pts and other solid tumors. Dose escalation has concluded and disease specific expansion cohorts are ongoing. Clinical trial information: NCT00871559.

The effect of preoperative nutritional status on postoperative outcomes in children undergoing surgery for congenital heart defects in San Francisco (UCSF) and Guatemala City (UNICAR)

The objective of this study was to determine the association between preoperative nutritional status and postoperative outcomes in children undergoing surgery for congenital heart defects (CHD). Seventy-one patients with CHD were enrolled in a prospective, 2-center cohort study. We adjusted for baseline risk differences using a standardized risk adjustment score for surgery for CHD. We assigned a World Health Organization z score for each subject's preoperative triceps skin-fold measurement, an assessment of total body fat mass. We obtained preoperative plasma concentrations of markers of nutritional status (prealbumin, albumin) and myocardial stress (B-type natriuretic peptide [BNP]). Associations between indices of preoperative nutritional status and clinical outcomes were sought. Subjects had a median (interquartile range [IQR]) age of 10.2 (33) months. In the University of California at San Francisco (UCSF) cohort, duration of mechanical ventilation (median, 19 hours; IQR, 29 hours), length of intensive care unit stay (median, 5 days; IQR 5 days), duration of any continuous inotropic infusion (median, 66 hours; IQR 72 hours), and preoperative BNP levels (median, 30 pg/mL; IQR, 75 pg/mL) were associated with a lower preoperative triceps skin-fold z score (P<.05). Longer duration of any continuous inotropic infusion and higher preoperative BNP levels were also associated with lower preoperative prealbumin (12.1 ± 0.5 mg/dL) and albumin (3.2 ± 0.1; P<.05) levels. Lower total body fat mass and acute and chronic malnourishment are associated with worse clinical outcomes in children undergoing surgery for CHD at UCSF, a resource-abundant institution. There is an inverse correlation between total body fat mass and BNP levels. Duration of inotropic support and BNP increase concomitantly as measures of nutritional status decrease, supporting the hypothesis that malnourishment is associated with decreased myocardial function.

Natriuretic peptides for early prediction of acute kidney injury in community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is common and associated with a considerable risk of acute kidney injury (AKI). MethodsWe prospectively enrolled 341 patients presenting to the emergency department with CAP (mean age 72, male 61%). Blinded measurements of three natriuretic peptides (NT-proBNP, MR-proANP and BNP) were performed upon presentation. The primary endpoint was the accuracy of the natriuretic peptides to predict AKI within 48h. ResultsAKI occurred in 24 patients (7.6%) within the first 48h. NPs and creatinine were significantly higher in AKI compared with patients without AKI (NT-proBNP 9517 [2042–26,792] vs 1177 [280–4167]pg/ml; MR-proANP 641 [196–1075] vs 182 [99–352]pmol/l; BNP 592 [230–1630] vs 160 [64–463]pg/ml; creatinine 166 [131–289] versus 100 [78–134]μmol/l, P<0.001 for each). Predictive accuracy as quantified by the area under the receiver operating characteristics curve was moderate to high: NT-proBNP 0.79 (95%CI 0.70–0.88), MR-proANP 0.78 (95%CI 0.67–0.88), BNP 0.74 (95%CI 0.63–0.85), creatinine 0.77 (95%CI 0.66–0.88). In multivariate logistic regression analysis, NPs remained the only independent AKI predictors: NT-proBNP (increase of 200pg/ml) OR=1.01, 95%CI 1.00–1.01, P=0.009; MR-proANP (increase of 100pg/ml) OR=1.23, 95%CI 1.09–1.39, P=0.001; BNP (increase of 100pg/ml) OR=1.08, 95%CI 1.03–1.14, P=0.002. ConclusionsNP levels are significantly elevated in CAP-patients experiencing early AKI. Their potential to predict early AKI is comparable to serum creatinine and might be useful in cases of diagnostic uncertainty.

Valor prognóstico do peptídeo natriurético tipo B na mortalidade de pacientes com Síndrome Coronariana Aguda

The prognostic value of BNP in acute coronary syndrome (ACS) has been repeatedly assessed, but not completely well established. Literature data for establishing the best time for assessing BNP, be it on hospital admission or after coronary intervention, are controversial. To analyze BNP in non-ST segment elevation ACS (NSTE-ACS) in the long term, and to assess the association between BNP (pg/ml), death, coronary anatomy, and TIMI Risk Score. Forty patients with NSTE-ACS and troponin>0.50 ng/ml had their BNP levels measured on admission and 96 hours after, and were followed up for four years. The difference between the two measures was assessed by use of Wilcoxon test (p<0.05). The ROC curve was used to evaluate 96-hour BNP accuracy as a death predictor, and logistic regression was used to assess a possible confounding factor among 96-hour BNP, age, and outcome. There was an increase in the 96-hour BNP (148 on admission vs. 267 after 96 hours; p=0.04). Thirteen patients died. For the 300 pg/ml cutoff, 96-hour BNP was a death predictor (sensitivity, 92.30%; specificity, 77.80%; positive predictive value, 66.70%; negative predictive value, 95.50%). The area under the ROC curve was 0.92. A 7.4-time increase in the relative risk of death in four years was observed with a 96-hour BNP> 300 pg/ml (95% CI 1.90 a 29.30 p<0.01). An association between 96-hour BNP and TIMI Risk Score was observed (p<0.01). An association was observed between the increase in 96-hour BNP and multivessel disease (p=0.02). In NSTE-ACS with positive troponin, 96-hour BNP can be a tool for risk stratification.

Effect of endurance and strength exercise on release of brain natriuretic peptide

Objectives:The aim of this study was to investigate the effects of 8-week endurance and resistance exercise training on release of brain natriuretic peptide.Materials and Methods:Study population was categorized into 4 groups: Group-1 (n = 6) consisted of sedentary individuals who volunteered to complete 8-weeks of endurance exercise; Group-2 (n=6) consisted of sedentary individuals who volunteered to complete 8-weaks of resistance exercise. Three blood samples [for Terminal pro BNP (NT-Pro-BNP)] were taken before, immediately after exercise and after 8 weeks of exercise training.Results:NT-Pro BNP was significantly increased immediately after endurance exercise [from 37.9 ± 1.4 pg/ml to 52.1 ±1.5 pg/ml; P = 0.002] and was decreased to 23.2 ± 9.3 pg/ml after 8 weeks of endurance exercise [P = 0.013]. On the other hand, NT-Pro BNP showed no significant changes immediately after resistance exercise [from 26.6 ± 4.9 pg/ml to 24.1 ±4.5 pg/ml; P = 0.553]. In contrast, NT-Pro BNP was significantly increased to 39.5 ±1.6 pg/ml after 8 weeks of resistance exercise [P = 0.012].Conclusion:Endurance exercise training reduces circulating NT-Pro BNP concentration, which is likely a marker of reduced ventricular wall tension and improved myocardial function. In contrast, strength exercise induces significant increase in NT-Pro BNP, which could be partially attributed to myocardial damage.

67 Spontaneous cardiac hypertrophy and adverse LV remodelling in a novel human relevant mouse model of diabetes; a mechanistic insight

<h3></h3> Heart failure (HF) is one of the commonest cardiovascular complications of Diabetes Mellitus (DM) with the prevalence of DM reported at around 30% in many pivotal heart failure studies. DM is an independent predictor of mortality in patients with HF, however molecular mechanisms that contribute to HF development in the diabetic population are poorly understood. Using a novel human relevant mouse model of DM (GENA348), identified through the MRC mouse mutagenesis programme with a point mutation in the pancreatic glucokinase (GLK) gene we investigate the molecular mechanisms that contribute to the HF phenotype in DM. GLK is the glucose sensor which regulates insulin secretion and GLK activity is reduced by 90% by the GENA348 point mutation resulting in severe hyperglycaemia. Similar mutations underlie Maturity Onset Diabetes of the Young Type 2 (MODY 2) in humans. Mean random blood glucose was found to be increased in the GENA348 mutant (HO) mice compared to wild type (WT) littermates (WT 6.9±0.3 mmol/l vs HO 20.6±0.8 mmol/l, p&lt;0.001). Serial echocardiography was performed, at 3, 6 and 12 months. No significant changes in echocardiographic parameters were observed at 3 months, although by 6 months development of significant cardiac hypertrophy in HO mice was observed. At 12 months of age left ventricular dilatation was evident, characterised by an 8% increase in diastolic diameter (WT 4.08±0.10 vs HO 4.41±0.12, p&lt;0.05). Systolic function was preserved although significant diastolic dysfunction was evident at 6 and 12 months with a 31% reduction in the E:A ratio. Histological staining illustrated significant cellular hypertrophy with real time PCR data demonstrating a relative 150% increase in the hypertrophic marker BNP. Hypertrophic pathways were examined through western blot analysis revealing an age dependant increase in Akt phosphorylation (3 months- no increase, 6 months-140%, 12 months-460%). Serum levels of advanced glycation end products (AGE) were also elevated by 86% (WT 21±3.5 ng/ml vs HO 39±8.3 ng/ml, p&lt;0.05) as was the protein expression level of the receptor for AGEs (RAGE). In vitro cellular experiments also revealed AGEs directly activate Akt through phosphorylation and increase levels of the receptor RAGE. AGE induced phosphorylation of Akt is inhibited in the presence of wortmannin, suggesting a PI3K dependent signalling mechanism. This was further confirmed in vivo where a bolus injection of wortmannin in 6-month old mutant mice returned Akt phosphorylation levels to those seen in WT mice. In conclusion, using the first human relevant mouse model of diabetes, GENA348 we demonstrate the development of a progressive cardiac phenotype including cardiac hypertrophy, LV dilatation and diastolic dysfunction similar to the clinical manifestations of diabetic cardiomyopathy. We propose that the RAGE/PI3K/Akt pathway contributes to the molecular mechanisms associated with the cardiac phenotype.

Electrophysiological effects of the natriuretic peptides BNP and CNP in the sinoatrial node and atrial myocardium

Natriuretic peptides (NPs), including ANP, BNP and CNP, constitute a family of hormones that elicit their effects by binding to three receptors denoted NPR-A, NPR-B and NPR-C. The electrophysiological effects of NPs in the heart, particularly in the specialized pacemaker cells of the sinoatrial node (SAN), are poorly understood; therefore, we have investigated the effects of BNP and CNP (10 and 100 nM) on isolated SAN and working atrial myocytes. BNP and CNP increased spontaneous action potential (AP) frequency and increased the slope of the diastolic depolarization in SAN myocytes. Voltage-clamp experiments demonstrate that these effects are the result of increases in the pacemaker current (If) and L-type Ca2+ current (ICa,L). In contrast to SAN myocytes, BNP had no effect on AP parameters in working atrial myocytes under basal conditions. Stimulation of atrial myocytes with isoproterenol (ISO; 10 nM) increased AP duration as well as ICa,L. Application of BNP following prestimulation with ISO further increased atrial myocyte AP duration and ICa,L. The effects of BNP and CNP on SAN myocytes are maintained in mutant mice lacking functional NPR-C receptors. These data suggest that BNP and CNP increase SAN myocyte firing frequency by activating the guanylyl cyclase-linked NPR-A and NPR-B receptors and that the sensitivity of the SAN to NPs is greater than the surrounding working myocardium.

Profiling B-type natriuretic peptide in a stable heart failure population: a valuable adjunct to care

To examine the prognostic importance of absolute values and change in values of BNP in patients with stable heart failure (HF). Five-hundred and fifty-nine patients attending a disease management programme were categorized into tertiles of BNP (group 1; ≤ 95 pg/ml, group 2; 96-249 pg/ml and group 3; ≥ 250 pg/ml). A change in BNP between two stable visits was recorded. Patients were followed up for 1 year for death and a composite morbidity measure of HF hospitalization, all-cause hospitalization, unscheduled visits for clinical deterioration(UC) of HF using survival analysis. The risk of the combined morbidity outcome increased with increasing tertiles of BNP (Log rank = 17.8 (2), p < 0.001). Furthermore, a 50 and 25% increase in BNP predicted morbidity in stable HF patients with an initial BNP > 200 pg/ml (p = 0.02) and > 450 pg/ml (p = 0.03), respectively. In a stable community HF population, an elevated BNP or an increase in BNP predicts an adverse prognosis thereby potentially identifying a population in need of closer clinical follow-up.

Tenascin-C May Be a Predictor of Acute Pulmonary Thromboembolism

Numerous studies have shown an increase in NT-pro BNP, troponin I and D-dimer levels with right ventricular dysfunction on echocardiography in patients with acute pulmonary thromboembolism (PTE). We found no data about the relation between tenascin-C and acute PTE in the litera-ture. The aim of this study was to evaluate tenascin-C levels in acute PTE and correlate them with NT-pro BNP, troponin I and D-dimer. Thirty-four patients who have massive or submassive PTE on spiral thorax CT (PTE group) and twenty healthy volunteers (non-PTE group) were evaluated. In all patients, right ventricular functions were obtained on transthoracic echocardiography and plasma tenascin-C, NT-pro BNP, troponin I, and D-dimer levels were measured. The left ventricular systolic diameter, left ventricular diastolic diameter and left ventricular ejection fraction were similar in the two groups. The right heart chamber sizes and main pulmonary artery diameter were significantly larger in the PTE group and systolic pulmonary artery pressures were also significantly higher in this group. Tenascin-C, NT-pro BNP, and D-dimer levels were also significantly higher in the PTE group than in the non-PTE group (p< 0.001). The troponin I levels did not differ between the two groups (p=0.4). Tenascin-C was found to be highly correlated with sPAP and NT-pro BNP and correlated with D-dimer; however, troponin I was not correlated with tenascin-C. This study demonstrates that tenascin-C may be an indicator of acute PTE.

B-type natriuretic peptides for prediction and diagnosis of weaning failure from cardiac origin

To evaluate and compare BNP and NT-proBNP concentrations to predict weaning failure from mechanical ventilation (MV) due to heart failure (HF) before a spontaneous breathing trial (SBT) and to identify HF as the cause of failure. Prospective, observational study in a university hospital. The sample included 100 patients on MV for over 48 h who underwent an SBT. Echocardiography and sampling for natriuretic peptides were performed immediately before and at the end of SBT. HF was diagnosed by pulmonary artery occlusion pressure >18 mm Hg or signs of elevated filling pressures in echocardiography. Thirty-two patients failed the SBT, 12 due to HF and 20 due to respiratory failure (RF). Before SBT, BNP and NT-proBNP were higher in patients failing due to HF than RF or in successfully weaned patients. Cut-off values using ROC curve analyses to predict HF were 263 ng/L for BNP (p < 0.001) and 1,343 ng/L for NT-proBNP (p = 0.08). BNP and NT-proBNP increased significantly during SBT in patients failing due to HF. Increases in BNP and NT-proBNP of 48 and 21 ng/L, respectively, showed a diagnostic accuracy for HF of 88.9 and 83.3% (p < 0.001). BNP performed better than NT-proBNP for HF prediction (p = 0.01) and diagnosis (p = 0.009). B-type natriuretic peptides, particularly BNP, can predict weaning failure due to HF before an SBT; increases in natriuretic peptides during SBT are diagnostic of HF as the cause of weaning failure. BNP performs better than NT-proBNP in prediction and diagnosis of HF.

Increases In B-Type Natriuretic Peptide (BNP) During Treatment with Lenalidomide In AL Amyloidosis

AbstractAbstract 3021The combination of lenalidomide and dexamethasone can produce partial and complete hematologic responses in previously treated patients with AL amyloidosis (Blood 2007; 109: 492–496). Since this prospective study was initiated, NT-proBNP and BNP have been found to be useful biomarkers for cardiac involvement, prognosis, and response to therapy in AL amyloidosis patients. Here we report on the retrospective analysis of the prospectively collected data on changes in BNP during lenalidomide therapy on this trial. Increase in BNP was defined as > 30% increase from baseline value at enrollment on the trial after cycles 1 and 3. Patients with BNP of < 100 pg/mL at baseline, and after 1 and 3 cycles as well as patients in whom BNP levels were not measured were excluded in this analysis. Sixty-eight patients with AL amyloidosis were treated with lenalidomide and dexamethasone (ClinicalTrials.gov: NCT00091260) at Boston Medical Center. The median age was 64 years (range, 42 to 85); and 69% were male. Fifty-one patients (75%) had lambda clonal plasma cell dyscrasia, and 38 (56%) had cardiac involvement. All patients received lenalidomide and dexamethasone as described in our previous report. Twenty-four of the 68 total patients enrolled did not meet the eligibility to be included in this analysis due to either BNP levels of < 100 pg/mL at baseline and at 1 and 3 months after treatment or unavailability of BNP measurement after 1 or 3 cycles of lenalidomide. Therefore, 44 patients are included in this analysis. Thirty-eight patients (86%) had > 30% increase in BNP level from baseline after initiation of lenalidomide treatment. Of these 38 patients, 30 (79%) had an increase after 1 cycle and additional 8 (21%) patients after 3 cycles of lenalidomide. The mean dose of lenalidomide for patients with increase in BNP after 1 cycle was 15 mg (range, 5–25) and after 3 cycles was 10 mg (range, 5–15). Forty % (n=12/30) and 63% (n=5/8) of patients did not receive dexamethasone with lenalidomide when increase in BNP was seen after 1 and 3 cycles, respectively. Of the patients with increase in BNP, only 5 patients (13%) had worsening of renal function from baseline. Moreover, increase in BNP after 1 and 3 cycles occurred in 23 of 29 patients (79%) with cardiac involvement. Cardiac troponin I levels were not measured after 1 and 3 cycles of lenalidomide. All the patients with increase in BNP were asymptomatic without association of modification in NYHA class congestive heart failure. The median survival of these 44 patients is 53 months since initiation of lenalidomide therapy. At these early time pointsof 1 and 3 months, 20% (n=9/44) of patients had >50% improvement in serum free light chain levels, and 2% (n=1/44) of patients had improvement in BNP of 30% or more. In conclusion, BNP increased by > 30% in a substantial proportion of patients with AL amyloidosis during treatment with lenalidomide. The mechanism for asymptomatic rise in BNP is not clear; however, the temporal relationship with lenalidomide initiation, the relatively rapid increase, and the absence of other identifiable precipitants for most of the patients suggest that lenalidomide may be playing a role. Moreover, patients with AL amyloidosis receiving lenalidomide whose BNP rises should not be assumed to be failing therapy without other signs of disease progression, but should be monitored closely and treated as needed for signs or symptoms of congestive heart failure should they occur. Disclosures:Off Label Use: Use of lenalidomide in AL amyloidosis. Zeldis:Celgene Corp: Employment.

Brain natriuretic peptide is related to diastolic dysfunction whereas urinary albumin excretion rate is related to left ventricular mass in asymptomatic type 2 diabetes patients

BackgroundThe aims of this study were to estimate the prevalence of left ventricular systolic (LVSD) and diastolic (LVDD) dysfunction, and to test if BNP and urinary albumin excretion rate (AER) are related to LVSD, LVD and left ventricular mass (LVM) in asymptomatic type 2 diabetes patients.MethodsPresence of LVSD, LVDD and LVM, determined with echocardiography, was related to levels of BNP and AER in 153 consecutive asymptomatic patients with type 2 diabetes.ResultsLVSD was present in 6.1% of patients whereas 49% (29% mild, 19% moderate and 0.7% severe) had LVDD and 9.4% had left ventricular hypertrophy. Increasing age (P < 0.0001) was the only independent variable related to mild LVDD whereas increasing BNP (P = 0.01), systolic blood pressure (P = 0.01), age (P = 0.003) and female gender (P = 0.04) were independent determinants of moderate to severe LVDD. AER (P = 0.003), age (P = 0.01) and male gender (P = 0.006) were directly and independently related to LVM.ConclusionAbout half of asymptomatic type 2 diabetes patients have LVDD. Of those, more than one third display moderate LVDD pattern paralleled by increases in BNP, suggesting markedly increased risk of heart failure, especially in females, whereas AER and male sex are related to LVM.

Effect of Short-Term Maximal Exercise on BNP Plasma Levels in Healthy Individuals

Many studies documented the relationship between elevated plasma concentrations of natriuretic peptides and cardiovascular diseases, especially heart failure. However, it is still uncertain whether physical exercise leads to a significant release of natriuretic peptide in healthy subjects. The aim of this study was to determine the effect of maximal physical activity on plasma BNP concentrations in healthy individuals within 3 hours after the short-term exercise. BNP plasma concentrations were measured in 15 healthy volunteers before, immediately after as well as 1 hour and 3 hours after bicycle spiroergometry. Maximal workload and exercise capacity were assessed in watts, watt-seconds, metabolic equivalents and VO(2max). Mean BNP plasma levels before, immediately after, 1 hour and 3 hours post-exercise were 19.4+/-2.5; 30.6+/-4.7; 17.9+/-2.5 and 18.7+/-3.1 pg/ml, respectively. The increase of BNP concentrations immediately after exercise was statistically significant (p=0.0017) compared to baseline values. We did not find any correlation between the post-exercise increase of BNP levels and age, body mass index, maximal workload or exercise capacity. In conclusion, short-term maximal physical exercise in healthy individuals led to a fast and transient rise of plasma BNP concentrations, which remained well within normal range and far below the cut-off value for heart failure (100 pg/ml).

Sodium Bicarbonate Prevents Increase of BNP in the Patients Undergoing Cardiac Catheterization

Sodium Bicarbonate Prevents Increase of BNP in the Patients Undergoing Cardiac Catheterization

Comprehensive Assessment of Rosiglitazone on Cardiac Safety in a Rat Model of Heart Failure

The antidiabetic drugs, PPARγ‐modulator class, are associated with severe cardiovascular risk. This liability has not been sufficiently explored in animal models. The present study was designed to assess cardiac safety biomarkers associated with a PPARγ agonist, rosiglitazone (Rosi), in rat heart failure (HF) model. HF was induced by coronary artery ligation and confirmed by ultrasound (US). Sham or HF rats were treated by low (3 mg/kg) or high (45 mg/kg) doses of Rosi, po, for 28 days. Biomarkers for heart structure and function (US), myocardial fibrosis, neuroendocrine biomarkers (BNP, aldosterone) and metabolic variables (glucose and insulin) were monitored. Targeted low‐density gene array was deployed to assess genomic responses. HF was marked by increase in BNP and ANP, low ejection fraction (30‐40%). Rosi effect was confirmed by increase in plasma adiponectin. Genomic analysis of model/treatment effects confirmed suppression by Rosi on ACE and TNFα expression. No evidence on exacerbation of cardiac function, structure and genomic change was noted in HF. ENaCs and Na+/Cl−/K+ transporters remained intact while marked increase in PPARγ expression was noted. Our data suggest that Rosi had no adverse effect on cardiac function in rat HF; instead, protective effect was suggested by decrease in ACE and ANP. These data suggest that cardiovascular risk of PPARγ need to be studied in non‐rodent models.

130: Values of C-reactive protein along with BNP increase when acute pulmonary cord occurs at a number of 60 patients

130: Values of C-reactive protein along with BNP increase when acute pulmonary cord occurs at a number of 60 patients

A One Unit Increase in Plasma BNP Is Associated with an Increased Odds of Hospital Admission in Patients with Congestive Heart Failure

A One Unit Increase in Plasma BNP Is Associated with an Increased Odds of Hospital Admission in Patients with Congestive Heart Failure

Use of B-Type Natriuretic Peptide in the Risk Stratification of Acute Exacerbations of COPD

In patients with COPD, prognosis might be determined at least in part by the extent of cardiac stress induced by hypoxia and pulmonary arterial hypertension. B-type natriuretic peptide (BNP), a quantitative marker of cardiac stress, was determined in 208 consecutive patients presenting to the emergency department with an acute exacerbation of COPD (AECOPD). The accuracy of BNP to predict death at a 2-year follow-up was evaluated as the primary end point. The need for intensive care and in-hospital mortality were determined as secondary end points. BNP levels were significantly elevated during the acute exacerbation compared to recovery (65 pg/mL; interquartile range [IQR], 34 to 189 pg/mL; vs 45 pg/mL; IQR, 25 to 85 pg/mL; p < 0.001), particularly in those patients requiring ICU treatment (105 pg/mL; IQR, 66 to 553 pg/mL; vs 60 pg/mL; IQR, 31 to 169 pg/mL; p = 0.007). In multivariate Cox regression analysis, BNP accurately predicted the need for ICU care (hazard ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.24 for an increase in BNP of 100 pg/mL; p = 0.008). In a receiver operating characteristic analysis to evaluate the potential of BNP levels to predict short-term and long-term mortality rates, areas under the curve were 0.55 (SD, 0.71; 95% CI, 0.41 to 0.68) and 0.56 (SD, 0.53; 95% CI, 0.45 to 0.66, respectively). In patients with AECOPD, BNP levels independently predict the need for intensive care. However, BNP levels failed to adequately predict short-term and long-term mortality rates in AECOPD patients.

Sepsis-associated diastolic dysfunction without elevated plasma B-type natriuretic peptide

Introduction: Plasma B-type natriuretic peptide concentration (BNP) is a marker of cardiac dysfunction [1]. It is unclear whyextremely high concentrations have been reported in sepsis with preserved systolic function [2]. This study sought to evaluaterelationships between BNP and in vivo diastolic function in a rat cecal ligation and perforation (CLP) model of sepsis.Methods: With institutional ethics committee approval (UQ AEC Protocol 675/05), 24 male Sprague–Dawley rats (518 ± 56 g)were studied. Rats were assigned to CLP (n = 12), sham surgery (sham, n = 6) or anaesthesia without surgery (control, n = 6). Echocardiography (15 MHz rodent probe) and venous blood sampling (BNP enzyme immunoassay) were performed prior to intervention (baseline; T0) and 18–22 hours following intervention (final; T2).Results: Prior to final evaluation, three CLP rats (25%) and one sham rat (during anaesthesia) died. Baseline differences between groups (ANOVA) were demonstrated for heart rate (HR) (CLP 340 ± 36 bpm, sham 351 ± 19 bpm, control 300 ± 12 bpm; P = 0.02), peak passive to active diastolic transmitral velocity ratio (E/A) (CLP 1.7 ± 0.65, sham 1.26 ± 0.27, control 2.34 ± 0.59; P = 0.048) and A velocity (CLP 0.574 ± 0.13 m/s, sham 0.733 ± 0.33 m/s, control 0.411 ± 0.07 m/s; P = 0.03). BNP was not significantly different between groups (CLP 0.676 ± 0.179 ng/ml; sham 0.719 ± 0.202 ng/ml; control 0.503 ± 0.006 ng/ml; P = 0.07). At T2, CLP was compared with sham and control (ANCOVA with adjustment for baseline values). Compared with control rats, CLP rats demonstrated higher HR (CLP 402 ± 46 bpm, control 305 ± 11 bpm; P = 0.003), higher A velocity (CLP 0.802 ± 0.152 m/s, control 0.501 ± 0.103 m/s; P = 0.01), and lower E/A (CLP 1.02 ± 0.23, control 1.74 ± 0.46; P = 0.004). BNP was not significantly different in the CLP group (CLP 0.743 ± 0.225 ng/ml, sham 0.756 ± 0.213 ng/ml (P = 0.3), control 0.509 ± 0.026 ng/ml (P = 0.7)). At T2, multiple linear regression with backward elimination yielded HR as the only independent predictor of BNP (adjusted r2 = 0.56, P < 0.001).Conclusions: In this model, sepsis was associated with echocardiographic evidence of diastolic dysfunction resemblingclinical sepsis without an associated increase in BNP. HR was an independent predictor of BNP, accounting for 56% of variation.

Abstract 2495: Pharmacodynamic Profile of a Novel Chimeric Natriuretic Peptide, CD-NP, as Compared to C-Type Natriuretic Peptide

Background: C-type natriuretic peptide (CNP), a 22-amino-acid peptide and a ligand of the natriuretic peptide receptor-B (NPR-B), exhibits venodilating, anti-fibrotic, and vascular-regenerating properties but limited renal actions. A Mayo-designed chimeric peptide, CD-NP, which consists of CNP and the C-terminus of Dendroaspis NP, was synthesized to test the hypothesis that CD-NP would possess CNP-like properties with an improved pharmacodynamic profile. Methods: Normal anesthetized dogs were given CD-NP 50 ng/kg/min (n = 10) or an equimolar dose of CNP 29.3 ng/kg/min (n = 9) i.v. for 75 min. Hemodynamic, renal, and hormonal data were obtained pre-infusion (pre-I), at 30 and 60 min I, and post-I, and were compared both within group vs pre-I (mean ± SE, P&lt; 0.05*, &lt; 0.01 † ) and between groups ( P &lt; 0.05 ‡ , &lt; 0.01 § , &lt; 0.001 ¶ ). Plasma BNP was measured by radioimmunoassay. Results: CD-NP resulted in greater increases in plasma cGMP (7±.4 to 25±3 †¶ to 36±3 †¶ to 23±3 †¶ pmol/ml), urinary cGMP excretion (978±145, 3170±205 †¶ , 5919±616 †¶ , 3077±298 †¶ pmol/min) vs CNP (8±.8, 10±.6 † , 11±.7 † , 8±.5 pmol/ml; 976±110, 1104±115, 1317±103, 998±101 pmol/min, respectively). CD-NP also increased urine Na + excretion (19±4, 168±24 †§ , 237±26 †¶ , 96±12 † μEq/min), urine flow (0.2±.1, 1.3±.2 † , 1.8±.3 † , 0.8±.2 † ml/min), and GFR (37±2 ‡ , 48±3 † , 51±3 † , 53±4 † ml/min) vs CNP (36±12, 68±10, 85±26, 81±25 μEq/min; 0.4±.1, 0.9±.2, 1.2±.3*, 0.9±.3 ml/min; 52±5, 53±7, 50±4, 49±6 ml/min, respectively). CD-NP reduced PCWP (5.7±.7, 4.1±1*, 3.2±.7 † , 4.3±.8 mmHg), RAP (1.8±.4, 1.1±.4 † , 0.9±.5 †§ , 1.3±.5 § mmHg), PAP (12±.6, 10±.4*, 10±.6, 11±.7 mmHg) vs CNP (6±.6, 5±.8, 6±.8, 7±.9 † mmHg; 2.6±.3, 2.5±.3 to 2.9±.3 to 3.5±.5 † mmHg; 13±1, 12±1, 12±1, 13±1 mmHg, respectively). Mean blood pressure was unchanged in either group. CD-NP increased circulating BNP during infusion vs CNP (40±4 vs 18±2 pg/ml, P&lt;0.001). Conclusion: This study demonstrates the successful transformation of CNP to a CNP-like peptide with enhanced natriuretic, diuretic, GFR-enhancing, and cardiac-unloading actions. CD-NP may also promote increases in plasma BNP which via the NPR-A receptor may contribute to its biological actions. The therapeutic potential of CD-NP in heart failure warrants further studies.