Human Brain Natriuretic Peptide Research Articles

Brain Natriuretic Peptide for Prevention of Contrast-Induced Nephropathy After Percutaneous Coronary Intervention or Coronary Angiography

BackgroundMany methods reportedly prevent contrast-induced nephropathy (CIN), but the effect of brain natriuretic peptide (BNP) on CIN is unknown. In this study we investigated recombinant BNP use before coronary angiography (CA) or nonemergent percutaneous coronary intervention (PCI) in patients with unstable angina. MethodsOne thousand patients with unstable angina were prospectively evaluated. The patients were randomly assigned to: group A, isotonic normal saline (NaCl 0.9%, 1 mL/kg/h) for 24 hours before CA or PCI; and group B, human recombinant BNP (rhBNP; 0.005 μg/kg/min). Serum creatinine (Scr) levels and estimated glomerular filtration rate were measured before and 24, 48, and 72 hours, and 7 days after the procedure. The primary outcome was CIN incidence defined according to a relative (≥ 25%) or absolute (≥ 0.5 mg/dL and 44 μmol/L, respectively) increase in Scr from baseline within 48 hours. The secondary end points were the changes in the Scr and estimated glomerular filtration rate, before and after the procedure. ResultsContrast volume, a history of diabetes mellitus, and BNP administration independently predicted CIN. The incidence of CIN was significantly greater in group A than in group B (14.8% vs 5.6%; P < 0.01). Renal function was less compromised in patients who received rhBNP. The Scr of all patients with CIN remained increased for 24 hours, but it was lower and recovered faster in patients who received rhBNP. ConclusionsrhBNP administration before CA or PCI protects renal function and can significantly decrease CIN incidence.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide.

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Protective effect of recombinant human brain natriuretic peptide on acute renal injury induced by endotoxin in canines.

The objective of this study was to evaluate the protective effect of recombinant human brain natriuretic peptide (rhBNP) on endotoxin-induced acute kidney injury (AKI) in canine model of septic shock and its potential mechanisms. Dogs with endotoxin-induced septic shock were subjected to intravenous infusion of saline solution or rhBNP at the concentrations of 5 μg/kg (low-dose intervention group) or 10 μg/kg (high-dose intervention group). At 0, 2, 4, 8, and 12 h, the systemic vascular resistance index (SVRI) as well as serum levels of high mobility group box 1 protein (HMGB-1) and creatinine were measured, and kidney tissue samples were taken for histological examination. We have found that low and high doses of rhBNP could significantly reduce kidney tissue damage, such as tubular epithelial swelling and atrophy, and interstitial cell swelling in response to LPS injection in the dog sepsis models. rhBNP administration significantly reduced SVRI and serum levels of creatinine in dogs with LPS-induced sepsis in a dose-dependent manner, and attenuated the rise in the circulating HMGB-1. In conclusion, these findings suggest that rhBNP may exert dose-dependent protective effect on kidney tissue with endotoxin-induced injury, and this effect may be associated with the changes in blood levels of HMGB-1. rhBNP may be considered as therapeutic agents for treating sepsis-induced AKI.

Clinical efficacy of lyophilized recombinant human brain natriuretic peptide in the treatment of patients with congestive heart failure

Objective To investigate the clinical efficacy and safety of lyophilized recombinant human brain natriuretic peptide(rhBNP) in the treatment of patients with congestive heart failure (CHF).Methods 120 CHF patients were randomly divided into two groups.58 cases in the observation group were given lyophilized rhBNP,and 62 patients in the control group were given sodium nitroprusside.The clinical effect,changes of echocardiographic indicators and hemodynamic parameters,adverse reactions were observed.Results After treatment,the total effective rate of the observation group was 91.37％,which was significantly higher than that of the control group(x2 =4.23,P ＜ 0.05).The LVEF and NT-proBNP levels in observation group were (59.0 ± 8.2)％ and (535.4 ± 123.8)ng/L,which had higher improvement than control group (P ＜ 0.05).The incidence rate of adverse reactions between the two groups had no significant difference (P＞ 0.05).Conclusion Lyophilized rhBNP in the treatment of CHF has significant effect,and it is worthy of clinical application and promotion. Key words: Heart failure, congestive; Natriuretic peptide,brain

Comparative effects of recombinant human brain natriuretic peptide and dobutamine on acute decompensated heart failure patients with differsent blood BNP levels

BackgroundRecombinant human B-type natriuretic peptide (rhBNP) has been indicated for the treatment of acute decompensated heart failure (ADHF). However, the therapeutic efficacy of intravenous rhBNP is not always satisfactory in patients with extremely high blood BNP levels. In this study, we evaluated the effects of rhBNP on patients with different BNP levels.MethodsOne hundred and five patients with ADHF whose left ventricular ejection fraction (LVEF) was <40%, were assigned to a high BNP group (BNP ≤ 3000 pg/mL) or an extra-high BNP group (BNP > 3000 pg/mL) , depending on their admission plasma BNP levels. Each group was then subdivided into rhBNP or dobutamine subgroups according to intravenous administration with either rhBNP or dobutamine for 24-72h. In the high BNP group, 58 patients were randomized to subgroup rhBNP (n = 28) and subgroup dobutamine (n = 30). In the extra-high BNP group, 47 patients were randomized to subgroup rhBNP (n = 24) and subgroup dobutamine (n = 23). The effects of rhBNP and dobutamine on patients in the high and extra-high BNP groups were compared.ResultsIn the high BNP group, rhBNP was more efficient than dobutamine at improving NYHA classification (P < 0.05), decreasing plasma BNP levels (P < 0.05), increasing LVEF (P < 0.05), and reducing hospital length of stay (P < 0.05). However, rhBNP displayed no superior therapeutic efficacy to dobutamine in the extra-high BNP group. Adverse cardiovascular events in patients treated with rhBNP were similar to adverse events in patients treated with dobutamine in both the high and extra-high BNP groups.ConclusionsrhBNP was more efficient than dobutamine at improving heart function in patients with ADHF when plasma BNP was ≤3000 pg/mL. However, rhBNP treatment showed no advantages over dobutamine when plasma BNP reached extremely high levels (>3000 pg/mL).Trial registrationClinicalTrials.gov Identifier: NCT01837849.

Protective effect of rhBNP on intestinal injury in the canine models of sepsis

Sepsis is the leading cause of death in the intensive care units worldwide. Proinflammatory cytokines such as TNF (tumor necrosis factor)-α and IL (interleukin)-6 mediate the pathogenesis of septic shock characterized by hemodynamic instability and end-stage multi-organ functional failure. Brain natriuretic peptide (BNP) has been used as a diagnostic and prognostic biomarker in the cardiovascular disorders. Most recently, plasma level of BNP has also been used to predict outcomes of critical illnesses including sepsis. We have recently reported that human recombinant BNP (rhBNP) could protect lungs from acute proinflammatory injury in response to LPS-injection. In the current study, using LPS (lipopolysaccharide)-induced canine sepsis models, we further investigated the effect of rhBNP on intestinal injury and its potential mechanisms. We have found that rhBNP (5μg or 10μg/kg weight) could significantly reduce intestinal tissue damage in response to LPS-injection in the dog sepsis models through down-regulating proinflammatory cytokines TNF-α and IL-6 (5-10 fold decrease compared to LPS-injection only group) by a mechanism of suppressing IκB phosphorylation and NF-κB expression. These findings suggest that BNP protect intestinal tissues from endotoxin-induced hyper-inflammatory injury and thus, may be used as therapeutic agents for sepsis.

The significance of natriuretic peptide in treatment of pulmonary hypertension after mitral valve replacement

To compare the therapeutic efficacy of recombinant human brain natriuretic peptide and prostaglandin E1 in the treatment of pulmonary hypertension after mitral valve replacement. Sixty patients with postoperative pulmonary hypertension were divided randomly into 3 groups that received saline, prostaglandin E1, and natriuretic peptide infusions for 12 hours each. The hemodynamics data were monitored consecutively, and the levels of thromboxane A2 and cyclic guanosine monophosphate were detected pretreatment, after treatment, and 1 week after surgery. The arterial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure decreased 1hour after prostaglandin E1 treatment and rebounded after treatment discontinuation. The pulmonary arterial pressure and pulmonary capillary wedge pressure in the natriuretic peptide group decreased 3 hours after treatment; pulmonary arterial pressure decreased less than that of the prostaglandin group, and there was no evidence of hemodynamic rebound after treatment discontinuation. The natriuretic peptide had no significant effects on arterial pressure. In both the prostaglandin and natriuretic peptide groups, cyclic guanosine monophosphate increased after the treatment, which was even higher in the latter group. Prostaglandin E1 could lead to the decrease of thromboxane A2, which was not seen in the natriuretic peptide group. Both brain natriuretic peptide and prostaglandin E1 can effectively reduce pulmonary hypertension; however, natriuretic peptide has a slower and milder efficacy. The effects of these 2 drugs in reducing thepulmonary arterial pressure may be mediated through different pathways.

GW24-e0320 Efficacy of intravenous recombinant human brain natriuretic peptide and noninvasive ventilation in treating the patients with acute decompensated heart failure

ObjectivesTo investigate the efficacy and safety of intravenous infusion recombinant human brain natriuretic peptide (rhBNP) with noninvasive ventilation (NIV) in treating patients with decompensated acute heart failure. To investigate the...

GW24-e1789 The Safety Research about rhBNP in Acute Myocardial Infarction Patients Undergoing Emergency PCI with Heart Failure and Mild Renal Insufficiency

ObjectivesThis research was designed for acute myocardial infarction patients with heart failure and mild renal insufficiency after pPCI, using recombinant human brain natriuretic peptide (rhBNP) contrasted with nitroglycerin (NIT), observe...

Protective effects of recombinant human brain natriuretic peptide against LPS-Induced acute lung injury in dogs

Acute lung injury (ALI) is a common component of systemic inflammatory disease without more effective treatments. However, recent studies have demonstrated that the recombinant human brain natriuretic peptide (rhBNP) has anti-inflammatory effects. Therefore, we found that rhBNP could prevent lipopolysaccharide (LPS)-induced acute lung injury in a dog model. Dogs were injected with LPS and subjected to continuous intravenous infusion (CIV) of saline solution or rhBNP. We detected the protective effects of rhBNP by histological examination and determination of serum cytokine levels and lung myeloperoxidase (MPO) activity and malondialdehyde (MDA) activity. Histological examination indicated marked inflammation, edema and hemorrhage in lung tissue taken 12h after rhBNP treatment compared with tissue from dogs which received saline treatment after LPS injection. LPS injection induced cytokine (IL-6 and TNF-α) secretion and lung MPO and MDA activities, which were also attenuated by rhBNP treatment. Inductions of IL-6 and TNF-α were significantly attenuated in the L-rhBNP and the H-rhBNP groups. The ratios of the L-rhBNP group and H-rhBNP group were lower than that in the lung injury group. Furthermore, MPO and MDA activities were significantly lower in the H-rhBNP group compared to those in the LI group. Our data indicate that rhBNP treatment may exert protective effects and may be associated with adjusting endogenous antioxidant enzymes. Thus, rhBNP may be considered as a therapeutic agent for various clinical conditions involving lung injury by sepsis.

Phage Display Generation of a Novel Humanized Single-Chain Antibody Against Brain Natriuretic Peptide with Potent Neutralizing Activity

Cerebral salt wasting syndrome (CSW) is defined as a renal loss of sodium and water during intracranial disease leading to hyponatremia, which is the most frequent electrolyte disorder in critically neurological patients. Abnormal brain natriuretic peptide (BNP) secretion is implicated as the main offender. Development of antagonist against BNP is therefore of potential clinical relevance. In this study, synthetic human BNP peptide (hBNP) was used as bait and a humanized single chain fragment variable (scFv) phage antibody library as the source of antagonists. After three rounds of biopanning, hBNP-specific phage clones were greatly enriched. The scFv gene from the best phage clone was inserted into pET-22b and expressed in Escherichia coli BL21 (DE3) PlysS cells. After purification by nickel-affinity and refolding, this scFv antibody (Ab) was proven to recognize hBNP specifically and sensitively in ELISA and dot-blotting assay. Its binding constant to hBNP was 1.98×10(-8) M, measured by surface plasmon resonance. Thus, the humanized scFv Ab prepared with this approach has potential therapeutic value for neutralizing abnormally high level of BNP correlated well with CSW.

Prevention of Contrast‐Induced Nephropathy in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review

To evaluate the current prophylactic strategies against CIN in patients with STEMI treated by primary percutaneous coronary intervention. Contrast-induced nephropathy (CIN) is the third leading course of acute renal failure and a recognized complication to cardiac catheterization. CIN is associated with increased risk of cardiac adverse events and mortality, and recent studies point at the risk of developing a transient or persistent renal dysfunction. Patients with ST-elevation myocardial infarction treated by primary percutaneous coronary intervention have a markedly increased risk of developing CIN. At present no strategy is universally accepted in the prevention of CIN in the acute setting of primary percutaneous coronary intervention. We performed a systematic search in Pubmed and EMBASE and ended up including nine randomised clinical trials; six studies of N-acetylcysteine, one study of early and late hydration regimens, one study of recombinant human brain natriuretic peptide and one study comparing a low-osmolar contrast agent with an iso-osmolar contrast agent. Recombinant human brain natriuretic peptide and the regimens of hydration significantly reduced the incidence of CIN and administration of N-acetylcysteine in one of the six studies significantly reduced the occurrence of CIN. The iso-osmolar contrast agent was not proven to be superior to the low-osmolar contrast agent in terms of preventing CIN. Preliminary studies are promising but further studies are needed before any prevention strategy against CIN can be recommended in routine care of patients undergoing primary percutaneous coronary intervention for STEMI.

A Novel Bioassay for the Activity Determination of Therapeutic Human Brain Natriuretic Peptide (BNP)

BackgroundRecombinant human brain natriuretic peptide (rhBNP) is an important peptide-based therapeutic drug indicated for the treatment of acute heart failure. Accurate determination of the potency of therapeutic rhBNP is crucial for the safety and efficacy of the drug. The current bioassay involves use of rabbit aortic strips, with experiments being complicated and time-consuming and markedly variable in results. Animal-less methods with better precision and accuracy should be explored. We have therefore developed an alternative cell-based assay, which relies on the ability of BNP to induce cGMP production in HEK293 cells expressing BNP receptor guanylyl cyclase-A.Methodology/Principal FindingsAn alternative assay based on the measurement of BNP-induced cGMP production was developed. Specifically, the bioassay employs cells engineered to express BNP receptor guanylyl cyclase-A (GCA). Upon rhBNP stimulation, the levels of the second messager cGMP in these cells drastically increased and subsequently secreted into culture supernatants. The quantity of cGMP, which corresponds to the rhBNP activity, was determined using a competitive ELISA developed by us. Compared with the traditional assay, the novel cell-based assay demonstrated better reproducibility and precision.Conclusion/SignificanceThe optimized cell-based assay is much simpler, more rapid and precise compared with the traditional assay using animal tissues. To our knowledge, this is the first report on a novel and viable alternative assay for rhBNP potency analysis.

Recombinant human brain natriuretic peptide therapy combined with bone mesenchymal stem cell transplantation for treating heart failure in rats

This study aimed to investigate the effects of combined recombinant human brain natriuretic peptide (rhBNP) therapy and bone mesenchymal stem cell (BMSC) transplantation on cell survival in myocardial tissues and on heart function in a rat model of heart failure (HF). Rat BMSCs were isolated, amplified and adherent cultured in vitro. A rat model of HF was established via the intraperitoneal injection of doxorubicin (Adriamycin). The rats were randomly divided into normal, HF, BMSC, rhBNP and BMSC plus rhBNP groups. The BMSCs were administered once via tail vein injection and rhBNP was infused via the jugular vein. Echocardiography and polygraphy were used to evaluate heart function. An enzyme‑linked immunosorbent assay was used to detect the changes in brain natriuretic peptide (BNP) concentration prior to and following intervention. Western blot analysis was used to detect the expression of the myocardium‑specific proteins GATA-binding protein 4 (GATA-4), connexin 43 (Cx43) and cardiac troponin I (cTnI). The results of cardiac echocardiography and the hemodynamic data show that various indicators of left ventricular systolic function in the BMSC plus rhBNP group were significantly improved compared with those in the other groups (P<0.05). No significant differences in the improvement of cardiac function were observed between the BMSC and rhBNP groups (P>0.05). Following treatment, a significant difference in BNP levels was observed between the BMSC plus rhBNP and the BMSC groups (P<0.05). The GATA-4, Cx43 and cTnI expression levels in the BMSC plus rhBNP group were higher than those in the BMSC group. Compared with rhBNP treatment, BMSC transplantation alone does not significantly improve heart function. However, combining rhBNP therapy and BMSC transplantation increases the expression levels of GATA-4 and other proteins to improve cardiac systolic and diastolic function.

Abstract 325: Brain Natriuretic Peptide During Coronary Intervention Prevents Endothelial Dysfunction Post PCI via NP-cGMP Activation

Background: Contrast media (CM) administrated during percutaneous coronary intervention (PCI) is associated with endothelial dysfunction (ED) and systemic vascular injury. Brain natriuretic peptide (BNP) administration 24 hours post PCI decreases ED. Aims: To evaluate 1.The ability of human BNP (hBNP) infusion during PCI, to prevent ED in acute coronary syndrome's (ACS) patients post the PCI. 2. The effect of CM on human coronary microvascular endothelial cells (HCMEC).3. Explain ED by invitro study. Methods and results (in vivo): Non-ST elevation ACS patients who underwent PCI (111) were randomized into 2 groups: an hBNP group who received hBNP infusion during the procedure (n=44), and control group who received nitroglycerin (n=67). Flow mediated dilatation (FMD) (by ≥2.5%), BNP, corin, serum creatinine (sCr) and estimate Glomerular Filtration Rate (eGFR), before and 24 hr after operative were recorded, starting with the same baseline. The post PCI FMD and eGFR were significantly reduced in the control group (p=0.05, 0.002) but not in the hBNP group (p=0.16, 0.4). BNP, corin and sCr increased significantly in the control group (p=0.001, 0.003, 0.0002 respectively) but not in hBNP group (p=0.09, 0.07, 0.18). Methods and results (in vitro): HCMEC were treated with CM (10%) in the presence and absence of BNP. eNOS, corin and cGMP levels were measured by ELISA and the results were compared to untreated cells. In both treatments eNOS was significantly reduced (p=0.001) and corin was significantly increased (p=0.002). cGMP was not affected by CM treatment (p=0.278), but was increased significantly (p=0.001) by hBNP combination. cGMP immuno-flourescence staining of HCMEC showed distorted cellular cGMP appearance by CM treatment, that was corrected in the combination with hBNP with accentuated subsarcolemmal staining. Conclusions: CM reduces eNOS level in HCMEC. Therefore, reduced in NO-cGMP pathway's products, probably is the mechanism that induces ED in-vivo. BNP treatment reduces FMD diminution and kidney injury post PCI. A compensatory rise in corin that increases BNP as well as the hBNP administration, invivo and invitro, maintains cytosolic cGMP via NP-cGMP pathway, and compensates for NO-cGMP loss, (reduced sGC) and thus prevents ED.

Changes in the content of some cytokines during chronic heart failure

Aim. To determine the changes in the content of cytokines, systolic intraventricular and interventricular dyssynchrony in patients with chronic heart failure. Methods. The study included 223 patients (174 males, 49 females) who suffered a Q wave myocardial infarction of the left ventricle, with clinical manifestations of chronic heart failure with functional class III according to the classification of the New York Heart Association. Pro- and anti-inflammatory cytokines (tumor necrosis factor alpha, interleukin-6, -4, and -10, interferon-gamma) were studied in blood plasma by enzyme immunoassay. Dyssynchrony was studied by pulsed-wave Doppler investigation, M-mode measurements of the left ventricle and pulsed-wave mode of tissue Doppler investigation of the myocardium. Results. Noted was an elevation of levels of tumor necrosis factor alpha, interleukin-6, interferon gamma, in combination with a reduction in the content of interleukin-4 and -10 in all groups. The maximum increase in the content of tumor necrosis factor alpha and interleukin-6 was found in the group of eccentric hypertrophy and dilatation of the left ventricle. Positive correleation links of medium strength have been established between the levels of interleukin-6 and the degree of interventricular mechanical delay, and between systolic and diastolic myocardial stress. In the group with eccentric hypertrophy and dilation of the left ventricle the content of tumor necrosis factor alpha directly correlated with the time interval from the beginning of the Q wave on the electrocardiogram to the beginning of the oflow in the left ventricular outflow tract, as well as with the concentration of N-terminal fragment of the precursor of the human brain natriuretic peptide. During remodeling according to the type of eccentric hypertrophy without dilatation of the left ventricle observed were positive correlation links of medium strength between the content of the tumor necrosis factor alpha and the intraventricular mechanical delay, end-diastolic pressure in the left ventricle. In the group of concentric hypertrophy the content of the tumor necrosis factor alpha and interleukin-6 is positively associated with electrocardiographic interval from the Q wave to the beginning of the systolic Doppler artifact S. Conclusion. One of the factors, which contributes to the preservation of abnormal levels of tumor necrosis factor alpha and interleukin-6 in blood plasma is the intraventricular and interventricular dyssynchrony; the combination of dilatation, myocardial hypertrophy, systolic and diastolic left ventricular dysfunction, dyssynchrony and the toxic effects of proinflammatory cytokines on the myocardium contributes to progression of chronic heart failure.

Clinical study of recombinant human brain natriuretic peptide in patients with acute myocardial infarction complicating congestive heart failure

ObjectiveTo observe the efficacy and safety of recombinant human brain natriuretic peptide (rh-BNP) on patients with acute myocardial infarction complicating congestive heart failure.MethodsForty patients with acute myocardial infarction complication by...

Renin is activated in monochorionic diamniotic twins with birthweight discordance who do not have twin-to-twin transfusion syndrome

To assess renin, aldosterone, human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) levels in cord blood from monochorionic diamniotic (MD) twins with a birthweight (BW) discordance that do not satisfy the criteria of twin-to-twin transfusion syndrome (TTTS). Cord blood samples were obtained from 28 MD twins without TTTS. They were divided into two groups on the basis of BW discordance as follows: large (>7.5%) and small (7.5%). Cord blood renin, aldosterone, hANP and BNP levels were measured. Renin levels in MD twins with a large BW discordance were significantly higher than those in MD twins with a small BW discordance, with no significant differences in aldosterone, hANP and BNP levels. A significant correlation was found between renin levels and BW discordance. Renin is activated in MD twins with a BW discordance of >7.5%, even in non-TTTS.

Expression, purification, and characterisation of nesiritide using an E. coli expression system

Nesiritide, the recombinant human brain natriuretic peptide, is involved in the regulation of cardiovascular homeostasis and has been approved for treatment of patients with congestive heart failure. We prepared a synthetic cDNA construct of Nesiritide to generate a fusion protein with an affinity handle and 41 amino acid peptide of β-galactosidase. The fusion protein was expressed mainly in the inclusion bodies and accounted for approximately 20% of total cellular protein. After purification by Ni-IDA affinity chromatography and renaturation, the fusion protein was cleaved with purified recombinant enterokinase. Nesiritide was purified by pH precipitation/ion exchange chromatography followed by source phenyl chromatography to obtain protein with > 99% purity (determined by RPHPLC) and a mass of 3,464 Daltons. The potency (ED50) of the purified protein was equivalent to that of Natrecor (Innovator formulation). Analytical methods were developed to identify oxidised, reduced and other related impurities. The expression strategy described in this work allows the convenient generation of high yield Nesiritide and enabled ease of purification.

Application study of recombinant human brain natriuretie peptide in the treatment of acute decompensated heart failure

Objective To investigate therapeutic effect and safety of recombinant human brain natriuretic peptide(rhBNP)in the treatment of acute decompensated heart failure.Methods Selectire patients with acute decompensated heart failure were randomly divided into control group(n=30)and rhBNP group(n=30):control group received typical conventional therapy,and rhBNP group received lyophilized rhBNP on the basis of conventional therapy with primingloading dose of 1.5 μg/kg iv and following dose of physical signs in both groups were observed,and the changes of heart rate,breath,blood pressure,urinary volume during 24 hours,left ventricular ejection fraction,renal function.NT-proBNP in both groups were recorded before and after treatment.Results The differences in baseline characteristics between two groups weren't significant.The total effective rate(96.7%)in rhBNP group was higher than that in control group(73.3%)(P＜0.05).Heart rate,blood pressure,CVP,NT-proBNP,urinary volume during 24 hours,left ventriculat ejection fraction after and before treatment were(99±6)bpm,(121±8)/(80±4)mmHg,(8.15±1.89)cmH2O,(3426.95±590.02)pg/mL,(1.8±0.4)L,(58±8)%and(135±10)bpm,(169±18)/(105±11)mmHg,(15.07±3.71)cmH2O,(5 989.44±983.48)pg/mL,(1.0±0.2)L,(29±6)%respectively in rhBNP group,the differences were significant(P＜0.05). There was no aggravation on renal function.Conclusima rhBNP is safe and effective in the treatment of acute decompensated heart failure. Key words: Recombinant human brain natriuretic peptide; Acute decompensated heart failure; Therapeutic effect