Corrigendum: Interferon-induced transmembrane protein 3 in the hippocampus: a potential novel target for the therapeutic effects of recombinant human brain natriuretic peptide on sepsis-associated encephalopathy.

[This corrects the article DOI: 10.3389/fnmol.2023.1182005.].

Recombinant human brain natriuretic peptide attenuates ischemic brain injury in mice by inhibiting oxidative stress and cell apoptosis via activation of PI3K/AKT/Nrf2/HO-1 pathway.

Ischemic stroke followed by cerebral artery occlusion is a main cause of chronic disability worldwide. Recombinant human brain natriuretic peptide (rhBNP) has been reported to alleviate sepsis-induced cognitive dysfunction and brain I/R injury. However, the function and molecular mechanisms of rhBNP in ischemic brain injury have not been clarified. For establishment of an animal model of ischemic brain injury, C57BL/6 mice were treated with middle cerebral artery occlusion (MCAO) surgery for 1 h and reperfusion for 24 h. After subcutaneous injection of rhBNP into model mice, neurologic deficits were assessed by evaluating behavior of mice according to Longa scoring system, and TTC staining was utilized to determine the brain infarct size of mice. The levels of oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA), were detected in hippocampal tissues of mice by corresponding kits. Cell apoptosis in hippocampus tissues was examined by TUNEL staining. Protein levels of antioxidant enzymes (HO-1 and NQO1) in cerebral cortex, apoptotic markers (Bax, Bcl-2, and cleaved caspase), and PI3K/AKT pathway-associated factors in hippocampus were tested by western blot analysis. The results revealed that injection of rhBNP decreased neurologic deficit scores, the percent of brain water content, and infarct volume. Additionally, rhBNP downregulated MDA level, upregulated the levels of SOD, CAT, and GSH in hippocampus of mice, and increased protein levels of HO-1 and NQO1 in the cortex. Cell apoptosis in hippocampus tissues of model mice was inhibited by rhBNP which was shown as the reduced TUNEL-positive cells, the decreased Bax, cleaved caspase-3, and cleaved caspase-9 protein levels, and the enhanced Bcl-2 protein level. In addition, rhBNP treatment activated the PI3K/AKT signaling pathway and upregulated the protein levels of HO-1 and NRF2. Overall, rhBNP activates the PI3K/AKT/HO-1/NRF2 pathway to attenuate ischemic brain injury in mice after MCAO by suppression of cell apoptosis and oxidative stress.

Comprehensive nursing intervention improves quality of life and reduces hospitalization time and expense in elderly patients with severe heart failure undergoing rh-BNP treatment.

OBJECTIVE: This study was designed to explore the efficacy of comprehensive nursing intervention in elderly patients with severe heart failure (SHF) treated by recombinant human brain natriuretic peptide (rh-BNP). METHODS: A retrospective analysis was made on 131 patients with SHF treated with rh-BNP in Wuhan Asia Cardiology Hospital from May 2019 to May 2022. Of them, 71 patients who received routine nursing care between May 2019 and December 2021 were assigned to the control group, and 60 patients who received comprehensive nursing between January 2022 and May 2022 were assigned to the observation group. The changes in quality of life (QoL) before and after nursing and the occurrence of adverse events after nursing were counted and compared between the two groups. The two groups were compared reagarding changes in anxiety and depression scores before and after nursing, as well as hospitalization expenses and hospitalization time. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) of patients were determined. The nursing satisfaction of the two groups was evaluated. Additionally, logistic regression was carried out to analyze the risk factors for adverse events. RESULTS: The control group had lower QoL scores than the observation group after nursing (P < 0.0001). The control group got significantly higher self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores than the observation group (P < 0.0001). The control group showed lower levels of LVEDV and LVEF than the observation group (P < 0.0001). The control group experienced greatly longer hospitalization time than the observation group, and also had a higher hospitalization expense than the observation group (P < 0.001). The observation group expressed much higher nursing satisfaction than the control group (P=0.007). Additionally, according to multivariate logistic regression analysis, age, hypertension, and diabetes mellitus were independent risk factors for adverse events (P < 0.05). CONCLUSION: For elderly SHF patients treated by rh-BNP, comprehensive nursing intervention can contribute to higher QoL, shorter hospitalization time, lower hospitalization expense, and milder negative emotions, but did not correlate with short-term adverse cardiovascular events.

Interferon-induced transmembrane protein 3 in the hippocampus: a potential novel target for the therapeutic effects of recombinant human brain natriuretic peptide on sepsis-associated encephalopathy.

Objective: This study aims to explore whether interferon-induced transmembrane protein 3 (IFITM3) is involved in recombinant human brain natriuretic peptide (rhBNP)-mediated effects on sepsis-induced cognitive dysfunction in mice. Methods: The cellular localization and expression level of IFITM3 in the hippocampus were detected. The IFITM3 overexpression was achieved using an intracranial stereotactic system to inject an adeno-associated virus into the hippocampal CA1 region of mice. Field experiments, an elevated plus maze, and conditioned fear memory tests assessed the cognitive impairment in rhBNP-treated septic mice. Finally, in the hippocampus of septic mice, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining and Immunoblot were used to detect changes in the protein expression of cleaved Caspase-8 and cleaved Caspase-3 in apoptosis-related pathways, and toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) p65 in inflammatory pathways. Results: Fourteen days after cecal ligation and puncture (CLP) surgery, IFITM3 localized in the plasma membrane and cytoplasm of the astrocytes in the hippocampus of septic mice, partially attached to the perivascular and neuronal surfaces, but not expressed in the microglia. The expression of IFITM3 was increased in the astrocytes and neurons in the hippocampus of septic mice, which was selectively inhibited by the administration of rhBNP. Overexpression of IFITM3 resulted in elevated anxiety levels and long-term learning and memory dysfunction, completely abolished the therapeutic effect of rhBNP on cognitive impairment in septic mice, and induced an increase in the number of neuronal apoptosis in the hippocampal CA1 region. The expression levels of cleaved Caspase-3 and cleaved Caspase-8 proteins were significantly increased in the hippocampus, but the expression levels of TLR4 and NF-κB p65 were not increased. Conclusion: The activation of IFITM3 may be a potential new target for treating sepsis-associated encephalopathy (SAE), and it may be one of the key anti-apoptotic mechanisms in rhBNP exerting its therapeutic effect, providing new insight into the clinical treatment of SAE patients.

Effect of recombinant human brain natriuretic peptide on acute kidney injury after coronary artery bypass grafting: a retrospective comparative cohort study.

Background: Acute kidney injury (AKI) is a common complication of coronary artery bypass grafting (CABG) that results in worse prognosis. Studies have shown that recombinant human brain natriuretic peptide (rh-BNP) reduces renal injury. However, its treatment effects for AKI in patients underwent cardiac surgery are unclear. This study sought to explore the efficacy of rh-BNP in patients with AKI after bypass surgery. Methods: This study included patients with AKI diagnosed within 4 days after CABG during the period January 2016 to December 2020. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The clinical characteristics and outcomes were collected. Patients were divided into BNP and non-BNP groups according to whether rh-BNP was injected intravenously after the operation. Multivariable logistic regression was adjusted the confounding effects between clinical characteristics and rh-BNP. Propensity score matching (PSM) was used to perform a sensitivity analysis. Results: A total of 395 patients, including 56 and 339 patients in the BNP and non-BNP groups, respectively, were included in this study. The decreasing trend of postoperative serum creatinine levels (P<0.001) and postoperative urine volume (P=0.001) within 4 days of surgery were independent associated with rh-BNP. From PSM, 175 patients, including 44 and 131 patients in the BNP and non-BNP groups, respectively, were included in this study. The decreasing trend of postoperative serum creatinine levels in the BNP group was significantly stronger than that in the non-BNP group (0.04±0.28 vs. -0.16±0.36, P=0.001). The postoperative urine volume within 4 days of surgery of the BNP group was higher than that of the non-BNP group (11.3±2.8 vs. 9.11±2.66, P<0.001). The cumulative dosage of diuretics after the procedure did not differ between the BNP and non-BNP groups {60 [40, 80] vs. 60 [40, 120], P=0.852}. Conclusions: Rh-BNP can reduce creatinine levels and increases postoperative urine volume to improve renal function in patients.

Recombinant human brain natriuretic peptide ameliorates venous return function in congestive heart failure.

AIMS: Recombinant human brain natriuretic peptide (rh-BNP) is commonly used as a decongestive therapy. This study aimed to investigate the instant effects of rh-BNP on cardiac output and venous return function in post-cardiotomy patients with congestive heart failure (CHF). METHODS AND RESULTS: Twenty-four post-cardiotomy heart failure patients were enrolled and received a standard loading dose of rh-BNP. Haemodynamic monitoring was performed via a pulmonary artery catheter before and after the administration of rh-BNP. The cardiac output and venous return functions were estimated by depicting Frank-Starling and Guyton curves. After rh-BNP infusion, variables reflecting cardiac congestion and venous return function, such as pulmonary artery wedge pressure, mean systemic filling pressure (Pmsf) and venous return resistance index (VRRI), reduced from 15 ± 3 to 13 ± 3 mmHg, from 32 ± 7 to 28 ± 7 mmHg and from 6.7 ± 2.6 to 5.7 ± 1.8 mmHg min m2 /L, respectively. Meanwhile, cardiac index, stroke volume index, and the cardiac output function curve remained unchanged per se. The decline in Pmsf [-13% (-22% to -8%)] and VRRI [-12% (-25% to -5%)] was much greater than that in the systemic vascular resistance index [-7% (-14% to 0%)]. In the subgroup analysis of reduced ejection fraction (<40%) patients, the aforementioned changes were more significant. CONCLUSIONS: rh-BNP might ameliorate venous return rather than cardiac output function in post-cardiotomy CHF patients.

A meta-analysis of the clinical efficacy of rhBNP in treating patients with acute myocardial infarction and heart failure.

OBJECTIVE: To explore the clinical efficacy of rhBNP in patients with acute myocardial infarction (AMI) and heart failure (HF). METHODS: A systematic review and a meta-analysis were performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. On May 30, 2020, we consulted the electronic databases PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane using the keywords "acute coronary syndrome (ACS)", "brain natriuretic peptide (BNP)", and "acute myocardial infarction (AMI)". The quality of the data included in the study was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. The results of the clinical randomized controlled study reports were analyzed using Review Manager 5.1.0. RESULTS: A total of nine, clinical, randomized, controlled studies were included. The effective rate in the rhBNP group was significantly higher than it was in the control group (Z = 9.50, P < 0.00001). The patients in the rhBNP group showed remarkably shorter hospital stays (Z = 24.43, P < 0.00001) and markedly increased left ventricular ejection fractions (LVEF) (Z = 245.53, P < 0.00001). Compared with the LVEF in the control group, the LVEF in the rhBNP group was significantly increased (Z = 3.55, P = 0.0004), but the rate of cardiac hypotension (Z = 3.55, P = 0.0004) and the headache incidence rate in the rhBNP group (Z = 2.3, P = 0.04) were not elevated. The rhBNP group showed no increase in either the low heart rate (Z = 1.22, P = 0.22) or the rate of renal insufficiency (Z = 0.35, P = 0.73). CONCLUSION: The meta-analysis suggests that, compared with the conventional treatment of patients with AMI and HF, rhBNP can markedly improve the clinical efficacy and myocardial functions and shorten the hospital stays, without elevating the rate of adverse reactions, such as hypotension, headaches, low heart rate, and renal insufficiency.

Protective effects of recombinant human brain natriuretic peptide on the myocardial injury induced by acute carbon monoxide poisoning.

BACKGROUND: To investigate the protective effect of recombinant human brain natriuretic peptide (rhBNP) on myocardial injury after acute carbon monoxide poisoning (ACOP). METHODS: We retrospectively reviewed medical records of patients with ACOP and high risk of cardiac events admitted to our hospital, and grouped them into rhBNP group and control group according treatments they received. Patients in control group received conventional treatment while those in rhBNP group were treated with rhBNP intravenously for 72 hours on the basis of conventional treatment. Levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), serum creatine kinase MB fraction (CK-MB), aldosterone (ALD), angiotensin II (AT II), and endothelin-1 (ET-1) prior to and after treatment of rhBNP or conventional treatment were collected. Corrected QT dispersion (QTcd) results were calculated based on the electrocardiography data. The left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVS), left ventricular ejection fraction (LVEF), and stroke output (SV) were measured using color Doppler echocardiography. Major adverse cardiovascular events (MACEs) that occurred within 1 month after treatment were recorded. RESULTS: A total of 135 patients in the rhBNP group and 136 patients in the control group were enrolled. Baseline characteristics between the two groups were similar at admission. Levels of cTnI, CK-MB, and ET-1 in the rhBNP group were significantly lower than those in the control group at day 1, 2 and 3 after treatment (P<0.05). Compared with the control group, levels of QTcd, ALD and AT II in the rhBNP group were significantly lower at day 3 after treatment (P<0.05). After 7 days of treatment, the reduction of NT-proBNP in the rhBNP group was significantly greater than that in the control group at each day (P<0.05), and LVEF, SV and LVEDD in the rhBNP group were all greater than those in the control group. After 1 month of treatment, the incidence of MACEs in the rhBNP group was significantly lower than that in the control group. CONCLUSIONS: For patients with ACOP and high risk of cardiac events, early treatment of rhBNP can protect injured cardiomyocytes, prevent the injury of carbon monoxide on heart, and reduce the incidence of MACE.

Beneficial effects of early administration of recombinant human B-type natriuretic peptide in ST-elevation myocardial infarction patients receiving percutaneous coronary intervention treatment.

INTRODUCTION: We aimed to evaluate the clinical performance of early administration of recombinant human B-type natriuretic peptide (rhBNP) to ST-elevation myocardial infarction (STEMI) patients receiving percutaneous coronary intervention (PCI) treatment. METHODS: In total, 185 patients diagnosed with STEMI were enrolled and randomised into either the placebo-treated (n = 88) or rhBNP-treated (n = 97) group. Patients were given either saline or rhBNP ten minutes before PCI and monitored with various cardiac parameters, including accelerated idioventricular rhythm, frequent ventricular premature beat (FVPB), ventricular tachycardia, systolic blood pressure, thrombolysis in myocardial infarction (TIMI) 3 gradation, corrected TIMI frame count (cTFC) and myocardial blush grade (MBG) 3 classification. RESULTS: Our results revealed no difference in accelerated idioventricular rhythm between the two groups. However, FVPB and ventricular tachycardia were significantly decreased in rhBNP-treated patients compared to placebo-treated patients (p < 0.05). Moreover, the occurrence ratio of reperfusion-associated low blood pressure in rhBNP-treated patients was lower than in placebo-treated patients (p = 0.03), while no difference was observed in infarction-related arteries TIMI 3 blood flow between the two groups (p = 0.23). Importantly, measurement of post-reperfusion blood flow velocity via cTFC suggested that rhBNP treatment could significantly increase blood circulation (p = 0.003). After stent implantation, the acquisition rate of MBG 3 was higher in rhBNP-treated patients compared to placebo-treated patients (p = 0.071), although the difference was not significant. CONCLUSION: We concluded that early administration of rhBNP can ameliorate the severity of reperfusion injury for STEMI patients receiving PCI treatment.

A rapid reporter assay for recombinant human brain natriuretic peptide (rhBNP) by GloSensor technology.

Accurate determination of biological activity is essential in quality control of recombinant human brain natriuretic peptide (rhBNP). In previous study, we successfully developed a genetically modified cell line 293GCAC3-based ELISA assay for rhBNP. But ELISA procedure is still tedious, so this study was aimed to develop a rapid and simple bioassay for rhBNP using GloSensor technology, which provides a platform of flexible luciferase-based biosensors for real-time detection of signaling events in live cells, including cGMP production. A reporter cell line 293GCAGlo-G1 was constructed by transfecting pGloSensor™ 40 F plasmid into 293GCAC3. The reporter assay based on 293GCAGlo-G1 showed high precision with intra-assay CV being 8.3% and inter-assay CV being 14.1%; high accuracy with 80%, 100% and 120% recovery rate being 99.2%, 102.4% and 99.0% respectively; and great linearity with R2 of linear fitting equation being 0.99. Besides, no significant difference was found in test results of reporter assay and 293GCAC3-based ELISA assay (paired t test, p = 0.630). All these results suggested that the reporter assay was a viable assay for biological determination of rhBNP.

A rapid reporter assay for recombinant human brain natriuretic peptide (rhBNP) by GloSensor technology / 药物分析学报

Accurate determination of biological activity is essential in quality control of recombinant human brain natriuretic peptide (rhBNP). In previous study, we successfully developed a genetically modified cell line 293GCAC3-based ELISA assay for rhBNP. But ELISA procedure is still tedious, so this study was aimed to develop a rapid and simple bioassay for rhBNP using GloSensor technology, which provides a platform of flexible luciferase-based biosensors for real-time detection of signaling events in live cells, including cGMP production. A reporter cell line 293GCAGlo-G1 was constructed by transfecting pGloSensor?40 F plasmid into 293GCAC3. The reporter assay based on 293GCAGlo-G1 showed high precision with intra-assay CV being 8.3% and inter-assay CV being 14.1%; high accuracy with 80%, 100% and 120% recovery rate being 99.2%, 102.4% and 99.0% respectively; and great linearity with R2of linear fitting equation being 0.99. Besides, no significant difference was found in test results of reporter assay and 293GCAC3-based ELISA assay (paired t test, p＝0.630). All these results suggested that the reporter assay was a viable assay for biological determination of rhBNP.

Continuous administration of recombinant human B-type natriuretic peptide can improve heart and renal function in patients after cardiopulmonary bypass surgery.

BACKGROUND: Any cardiac surgery under cardiopulmonary bypass (CPB) will induce ischemia-reperfusion injury and systematic inflammatory response, which may lead to exacerbation. Conventional therapy strategy is to use inotropes, diuretics and vasodilator drugs, yet, the therapeutic effects of which need to be improved. Recombinant human B-type natriuretic peptide (rhBNP) has been shown to be efficacious in the treatment of acute decompensated heart failure and acute myocardial infarction. However, the effects of rhBNP on patients carried out CPB surgery is unknown. METHODS: We retrospect 357 patients carried out CPB surgery between Jan 1st 2014 and Dec 31st 2015 of our department. And according the use of rhBNP, these patients were divided into two groups: rhBNP group and control group. Patients in rhBNP group were received continuous intravenous rhBNP (0.0075-0.01 µg/kg/min) in 6 hours after CPB surgery, for a period of 72 h. Hemodynamic parameters were measured immediately after CPB surgery, and then at 2, 4, 8, 12 and 24 h after surgery. Blood samples were obtained immediately after surgery and thereafter once a day at 6:00 AM within the first 3 days after surgery. The daily urine volume as well as the time of tracheal intubation, ICU stay and chest drainage were also recorded. RESULTS: The baseline characteristics and heart functions were well balanced between two groups, and no patient died in the surgery. It showed significant differences in time-dependent changes in both groups of MAP (P<0.0001, within groups), MPAP (P<0.0001, within groups), PAWP (P<0.0001, within groups), CI (P<0.0001, within groups), SVRI (P<0.0001, within groups), serum BNP (P<0.0001, within groups), CK-MB (P<0.0001, within groups), troponin (P<0.0001, within groups) and creatinine (P<0.0001, within groups). It also showed significant differences in time-dependent changes between the two groups of MAP (P=0.04, between groups), PAWP (P=0.04, between groups), serum troponin (P<0.0001, between groups), serum creatinine (P<0.0001, between groups) and urine volume (P<0.0001, between groups). Interestingly, our results showed that patients in rhBNP group tended to wean off the respirator half a day later than those in control group (P=0.05), while no significant difference showed in both the length of chest drainage time and intensive care unit stay between the two groups. CONCLUSIONS: The administration of rhBNP can improve heart and renal function in patients underwent CPB surgery as well as accelerating the recovery from myocardial injury. But the prognosis of the patients who were administrated rhBNP did not improve in our study.

Impact of rhBNP infusion on early postoperative recovery after total cavo-pulmonary connection surgery / 中华胸心血管外科杂志

Objective To compare the effects of rhBNP on the discharge time and pleural effusion in children with total cavo-pulmonary connection, and to provide a more reasonable method for the clinical treatment of postoperative children. Meth-ods Retrospective analysis of Jan 2016 to Jan 2017 during the hospital 40 cases of complex congenital heart disease in children with total cavo-pulmonary connection clinical data, of which 5 cases due to postoperative thrombosis or postoperative venous pressure was too high and had a second Fontan surgery, the patients excluded from the inclusion criteria. 9 cases of children re-turned to the ward after surgery, such as cardiac, diuretic and other conventional treatment based on the application of unequal dose of rhBNP(3-11 days) for the rhBNP group, 26 cases of conventional treatment of children with conventional treatment group. By comparing the early postoperative survival rate, the number of days of hospital stay and the retention time of the tho-racic drainage between the two groups. Results There were no significant differences in the time of cardiopulmonary bypass, postoperative ventilator use time, ICU time and positive inotropic drug scores in all the two groups. All the patients underwent preoperative examination with total cavo-pulmonary connection were alive and healthy discharge. The median hospital stay was 18 days in the rhBNP group(11-33 days, mean 19. 2 days), and the median length of hospital stay was 28 days in the routine treatment group(9 to 95 days, mean 34. 4 days). The difference of hospitalization days between the two groups was statistically significant(P=0. 038). In the retention time of the thoracic drainage tube, the median thoracic drainage tube retention time was 14 days(9-27 days, mean 15. 6 days) in the rhBNP group and 23 days in the conventional treatment group(7-91 days, mean 30. 9(P=0. 046). All the patients had no adverse effects such as excessive fluid load, intractable hypotension and liver or kidney function injury. Conclusion RhBNP can be used safely in pediatric cardiac surgery. Compared with the convention-al treatment group, rhBNP has advantages in the early discharge time and the time of thoracic drainage tube removal in children with total cavo-pulmonary connection.

Effects of rhBNP after PCI on non-invasive hemodynamic in acute myocardial infarction patients with left heart failure.

OBJECTIVE: To investigate the effects of exogenous recombinant human brain natriuretic peptide (rhBNP) after primary percutaneous coronary intervention (PCI) on non-invasive hemodynamic in acute myocardial infarction patients with left ventricular failure. METHODS: A number of 96 acute myocardial infarction patients accompanied with heart failure after PCI hospitalized in the People's Hospital of Sanya during February 2012 to October 2015 were selected. They were randomly divided into the therapy group (n = 50) and control group (n = 46). On the basis of routine treatment, patients in the therapy group were treated with intravenous rhBNP (1.5 µg/kg was intravenous injection with uniform speed of 3 min, followed by continuous infusion 0.0075 µg/kg·min for 72 h), while the control group received conventional treatment. BioZ-2011 non-invasive hemodynamic real-time monitoring system was used to monitor the hemodynamic parameters changes and the leaves of plasma pro-BNP, serum creatinine, serum potassium, serum sodium and urine volume of each group before and after treating for 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 72 h. RESULTS: Patients in the therapy group showed no effect on heart rate, while after 30 min of intravenous injection of rhBNP, CO, CI, SV, and SI increased significantly and LVET and TFC reduced at the same time, which had certain effect on blood pressure (SBP/DBP). Compared with the control group, the therapy group showed a faster and more effective improvement on hemodynamics. CONCLUSIONS: Acute myocardial infarction patients complicated with left heart failure after primary PCI can significantly improve hemodynamics by treating with rhBNP.

Effect of rhBNP on renal function in STEMI-HF patients with mild renal insufficiency undergoing primary PCI.

This study aims to investigate the effect of recombinant human brain natriuretic peptide (rhBNP) on renal function and contrast-induced nephropathy (CIN) incidence in ST-segment elevation myocardial infarction and heart failure (STEMI-HF) patients with mild renal insufficiency undergoing primary percutaneous coronary intervention (PCI). A total of 116 participants were randomized into rhBNP (rhBNP, n = 57) and nitroglycerin group (NIT, n = 59), receiving intravenous rhBNP or nitroglycerin from admission to 72 h after PCI. Renal function was assessed by serum creatinine (SCr), estimated glomerular filtration rate (eGFR), Cystatin-C (Cys-C) and ß2-microglobulin before and after primary PCI, and calculated the incidence of CIN within 72 h after PCI. There were no significant differences in SCr, eGFR and ß2-microglobulin between the two groups (P > 0.05, respectively). Compared with the NIT group, the total urinary volume within 72 h was higher while the level of Cys-C at 24 and 72 h after PCI was lower in the rhBNP group. rhBNP was associated with a decline in the incidence of CIN (12.28 vs. 28.81 %, P < 0.05). No differences were detected in mortality and re-hospitalization in 3 months between the two groups. The incidence of renal injury was not different between rhBNP and nitroglycerin in STEMI-HF patients with mild renal insufficiency. However, infusion of rhBNP was associated with a decline in incidence of CIN.

Effects of rhBNP after PCI on non-invasive hemodynamic in acute myocardial infarction patients with left heart failure

Objective To investigate the effects of exogenous recombinant human brain natriuretic peptide (rhBNP) after primary percutaneous coronary intervention (PCI) on non-invasive hemodynamic in acute myocardial infarction patients with left ventricular failure. Methods A number of 96 acute myocardial infarction patients accompanied with heart failure after PCI hospitalized in the People's Hospital of Sanya during February 2012 to October 2015 were selected. They were randomly divided into the therapy group (n = 50) and control group (n = 46). On the basis of routine treatment, patients in the therapy group were treated with intravenous rhBNP (1.5 μg/kg was intravenous injection with uniform speed of 3 min, followed by continuous infusion 0.007 5 μg/kg·min for 72 h), while the control group received conventional treatment. BioZ-2011 non-invasive hemodynamic real-time monitoring system was used to monitor the hemodynamic parameters changes and the leaves of plasma pro-BNP, serum creatinine, serum potassium, serum sodium and urine volume of each group before and after treating for 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 72 h. Results Patients in the therapy group showed no effect on heart rate, while after 30 min of intravenous injection of rhBNP, CO, CI, SV, and SI increased significantly and LVET and TFC reduced at the same time, which had certain effect on blood pressure (SBP/DBP). Compared with the control group, the therapy group showed a faster and more effective improvement on hemodynamics. Conclusions Acute myocardial infarction patients complicated with left heart failure after primary PCI can significantly improve hemodynamics by treating with rhBNP.

Clinical Observation of rhBNP Combined with Levosimendan in the Treatment of Acute Heart Failure / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of rhBNP combined with levosimendan in the treatment of acute heart failure,and to investigated the effects of drug combination on serum UA and BNP levels. METHODS:68 patients with acute heart failure were randomly divided into observation group and control group,with 34 cases in each group. Both groups re-ceived routine treatment;control group was additionally given Levosimendan injection 5 ml added into 0.9% Sodium chloride in-jection 45 ml with persistent micropump injection:at pump rate of 12 μg/(kg·min)within first 1 h,and then at pump rate of 0.5μg/(kg·min)for consecutive 23 h;observation group was additionally given rhBNP 1.5 μg/kg for intravenous shock,and then giv-en consecutive intravenous injection of rhBNP at rate of 7.5 ng/(kg·min)continuous 3-7 days on the basis of control group. Clini-cal efficacy of 2 groups were observed,and serum levels of UA and BNP,heart function index,the safety of drug use were ob-served before and after treatment. RESULTS:After treatment,total effective rate of observation group(94.11%)was significantly higher than that of control group (70.59%),with statistical significance (P0.05). CONCLUSIONS:rhBNP combined with levosimendan have significant clinical efficacy and high safety in the treatment of acute heart failure.

Effects of rhBNP after PCI on non-invasive hemodynamic in acute myocardial infarction patients with left heart failure

OBJECTIVE@#To investigate the effects of exogenous recombinant human brain natriuretic peptide (rhBNP) after primary percutaneous coronary intervention (PCI) on non-invasive hemodynamic in acute myocardial infarction patients with left ventricular failure.@*METHODS@#A number of 96 acute myocardial infarction patients accompanied with heart failure after PCI hospitalized in the People's Hospital of Sanya during February 2012 to October 2015 were selected. They were randomly divided into the therapy group (n = 50) and control group (n = 46). On the basis of routine treatment, patients in the therapy group were treated with intravenous rhBNP (1.5 μg/kg was intravenous injection with uniform speed of 3 min, followed by continuous infusion 0.0075 μg/kg·min for 72 h), while the control group received conventional treatment. BioZ-2011 non-invasive hemodynamic real-time monitoring system was used to monitor the hemodynamic parameters changes and the leaves of plasma pro-BNP, serum creatinine, serum potassium, serum sodium and urine volume of each group before and after treating for 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 72 h.@*RESULTS@#Patients in the therapy group showed no effect on heart rate, while after 30 min of intravenous injection of rhBNP, CO, CI, SV, and SI increased significantly and LVET and TFC reduced at the same time, which had certain effect on blood pressure (SBP/DBP). Compared with the control group, the therapy group showed a faster and more effective improvement on hemodynamics.@*CONCLUSIONS@#Acute myocardial infarction patients complicated with left heart failure after primary PCI can significantly improve hemodynamics by treating with rhBNP.

Clinical Efficacy of rh-BNP Combined with Continuous Renal Replacement Therapy on Refractory Heart Failure in Cardiorenal Syndrome / 中国药师

Objective:To observe the clinical efficacy of rh-BNP combined with continuous renal replacement therapy on the re-fractory heart failure in cardiorenal syndrome. Methods:Totally 48 patients with refractory heart failure in cardiorenal syndrome in our hospital were selected and randomly divided into the observation group and the control group. The control group was received the con-ventional drug therapy combined with continuous renal replacement therapy, and the observation group was received rh-BNP therapy ad-ditionally. After 7 days, NT-ProBNP, heart rate, LVEF, SV, BUN, Scr and GFR of the two groups were compared, and the clinical efficacy of the two groups was evaluated. Results:After the treatment, all the observed indicators in the two groups were significantly improved than those before the treatment, and the improvement in the observation group was better than that in the control group ( P<0. 05). The total effective rate of the observation group was higher than that of the control group(91. 67% vs 79. 17%, P<0. 05). Conclusion:The combination of rh-BNP and continuous renal replacement therapy can improve heart and kidney function of the refrac-tory heart failure in cardiorenal syndrome with better efficacy.

Effects of rhBNP on myocardial fibrosis after myocardial infarction in rats.

PURPOSE: We aimed to observe the effects and mechanism of rhBNP treatment on myocardial fibrosis (MF) after myocardial infarction (MI). METHODS: SPF rats were separated into 3 groups: normal, MI (ligation of left coronary artery), and MI + rhBNP (recombinant human brain natriuretic peptide). Rats in MI + rhBNP group were given 30 µg/kg for 2 days before modeling and for 4 weeks after modeling. mRNA levels and the expression levels of TGF-ß1 (transforming growth factor) and CTGF (connective tissue growth factor) in 3 groups were analyzed using the RT-qPCR and western blotting analysis, respectively. Furthermore, myocardial volume fraction (CVF) was analyzed using the Sirius Red F3B (SR) while the percentage of type I and III collagen in 3 groups were analyzed using the immunohistochemical staining. RESULTS: Compared with the normal group, the levels of TGF-ß1, CTGF, CVF, type I and III collagen were higher in MI group. However, mRNA levels of TGF-ß1 and CTGF were significantly decreased in MI + rhBNP compared to MI groups. Expression of TGF-ß1 was lower while that of CTGF was higher in MI + rhBNP group than that in MI group. Besides, CVF, and type I and III collagen were lower in MI + rhBNP group compared with MI group. CONCLUSION: rhBNP could significantly decrease the TGF-ß1 and CTGF levels in post-MI so as to inhibit the type I and III collagen deposition in MF of post-MI. rhBNP will be benefit for the improvement of MF.