The Association between Echocardiographic Parameters of Heart Failure with Preserved Ejection Fraction and Fluid Status Biomarkers in Hemodialysis Patients.

Overhydration and cardiac function abnormalities are common in hemodialysis patients. The association of N-terminal prohormone for brain natriuretic peptide (NT-proBNP) and other fluid status biomarkers with echocardiographic parameters of heart failure with preserved ejection fraction (HFpEF) is scarcely investigated in this population. A total of 100 separate measurements performed in 50 dialysis patients (29 male, aged 60 ± 17 years) in NYHA class II/II and preserved left ventricle ejection fraction were analyzed. Plasma levels of NT-proBNP, mid-regional prohormone for atrial natriuretic peptide (MR-proANP) and copeptin (CPP) were measured. The E/e' ratio as an index of HFpEF and other echocardiographic parameters were calculated. An E/e' ratio >9 was associated with higher median right ventricular systolic pressure (RVSP) and LVMI values. Left atrium volume index (LAVI) as well as NT-proBNP and MR-proANP, but not CPP levels were significantly higher in this group. In a stepwise multivariate analysis, only CPP and IL-6 levels were found to be independently associated with the E/e' ratio in the study group, whereas NT-proBNP and MR-proANP were associated only with left heart structure parameters and LVEF. Of the analyzed biomarkers, only the CPP level was found to be independently associated with the E/e' ratio in maintenance hemodialysis patients.

Coexisting transthyretin and atrial natriuretic peptide amyloid on left atrium in transthyretin amyloid cardiomyopathy.

Atrial amyloidosis is primarily caused by atrial natriuretic peptide (ANP) amyloid deposition. The main precursor protein causing cardiac amyloidosis is transthyretin (TTR), also known as TTR amyloid cardiomyopathy (ATTR-CM). A 73-year-old man, who presented with external dyspnea, was diagnosed with decompensated heart failure due to atrial fibrillation and severe mitral regurgitation. Left ventricular hypertrophy and elevated levels of high-sensitivity cardiac troponin T indicated cardiac amyloidosis. 99mtechnetium pyrophosphate scintigraphy findings and cardiac magnetic resonance imaging in the absence of monoclonal proteins were consistent with those of ATTR-CM. The patient underwent mitral valve repair, a maze procedure, and left atrial appendage (LAA) excision. While the histological analysis of the sampled left ventricular tissue led to diagnosis of ATTR-CM, the histological analysis revealed the coexistence of ANP and TTR amyloid deposition in the resected LAA. We report a case of ATTR-CM in which TTR and ANP amyloid deposition coexisted in the surgically resected LAA, indicating that both TTR and ANP amyloid correlate with atrial amyloidosis development in ATTR-CM. Learning objectives: Atrial natriuretic peptide (ANP) and transthyretin (TTR) amyloids can coexist in the same atrium. Not only TTR amyloids but also ANP amyloids can be correlated with the development of atrial amyloidosis in TTR amyloid cardiomyopathy with subsequent increased risk of atrial fibrillation.

Sildenafil Effect on Atrial Natriuretic Peptide Level in Pulmonary Hypertensive Rats.

BACKGROUND: Pulmonary Hypertension (PH) leads to changes in pulmonary vascular architecture, hypertrophy of the right ventricle, and heart failure. Sildenafil is a drug that can modulate PH by inducing smooth muscle relaxation and vasodilation. AIMS: To investigate the ability of sildenafil to alleviate the monocritaline (MCT)-induced PH in rats and to estimate the role and its effect on the atrial natriuretic peptide (ANP) levels. METHODS: 28 adult male rats were divided randomly into four groups: Group A (control group; n=7). Group B (MCT-treated group; n=7) was given a single dose of MCT 60 mg/kg subcutaneously. Group C (The reversal group; n=7) received a single dose of MCT 60 mg/kg subcutaneously for three weeks and then sildenafil at 50 mg/kg/day, given daily for another three weeks. Group D (The prevention group; n=7) simultaneously received a single dose of MCT 60 mg/kg subcutaneously and sildenafil daily at 50 mg/kg for three weeks. RESULTS: The animals in the prevention group showed a significant decrease in ANP levels compared to the reversal and MCT-treated groups. This decrease was associated with a significant reduction in the Fulton index ratio in the prevention group compared to the reversal group. The nitric oxide levels were also significantly higher in the reversal group than in the control group. CONCLUSION: Preventive sildenafil treatment was associated with a significant decrease in ANP levels and reduced MCT-induced cardiac hypertrophy in rats.

Atrial Natriuretic Peptide Alleviates Motion Sickness Potentially through Regulating Endolymph Volume in the Inner Ear Increased by Arginine Vasopressin.

INTRODUCTION: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP). METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. RESULTS: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. CONCLUSION: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.

Effectiveness of Copeptin, MR-proADM and MR-proANP in Predicting Adverse Outcomes, Alone and in Combination with Traditional Severity Scores, a Secondary Analysis in COVID-19 Patients Requiring Intensive Care Admission.

Objective: To investigate whether copeptin, MR-proADM and MR-proANP, alone or integrated with the SOFA, MuLBSTA and SAPS II scores, are capable of early recognition of COVID-19 ICU patients at increased risk of adverse outcomes. Methods: For this predefined secondary analysis of a larger cohort previously described, all consecutive COVID-19 adult patients admitted between March and December 2020 to the ICU of a referral, university hospital in Northern Italy were screened, and clinical severity scores were calculated upon admission. A blood sample for copeptin, MR-proADM and MR-proANP was collected within 48 h (T1), on day 3 (T3) and 7 (T7). Outcomes considered were ICU and in-hospital mortality, bacterial superinfection, recourse to renal replacement therapy (RRT) or veno-venous extracorporeal membrane oxygenation, need for invasive mechanical ventilation (IMV) and pronation. Results: Sixty-eight patients were enrolled, and in-hospital mortality was 69.1%. ICU mortality was predicted by MR-proANP measured at T1 (HR 1.005, 95% CI 1.001-1.010, p = 0.049), although significance was lost if the analysis was adjusted for procalcitonin and steroid treatment (p = 0.056). Non-survivors showed higher MR-proADM levels than survivors at all time points, and an increase in the ratio between values at baseline and at T7 > 4.9% resulted in a more than four-fold greater risk of in-hospital mortality (HR 4.417, p < 0.001). Finally, when considering patients with any reduction in glomerular filtration, an early copeptin level > 23.4 pmol/L correlated with a more than five-fold higher risk of requiring RRT during hospitalization (HR 5.305, p = 0.044). Conclusion: Timely evaluation of MR-proADM, MR-proANP and copeptin, as well as changes in the former over time, might predict mortality and other adverse outcomes in ICU patients suffering from severe COVID-19.

Structural insight into hormone recognition by the natriuretic peptide receptor-A.

Atrial natriuretic peptide (ANP) plays a central role in the regulation of blood pressure and volume. ANP activities are mediated by natriuretic peptide receptor-A (NPR-A), a single-pass transmembrane receptor harboring intrinsic guanylate cyclase activity. This study investigated the mechanism underlying NPR-A-dependent hormone recognition through the determination of the crystal structures of the NPR-A extracellular hormone-binding domain complexed with full-length ANP, truncated mutants of ANP, and dendroaspis natriuretic peptide (DNP) isolated from the venom of the green Mamba snake, Dendroaspis angusticeps. The bound peptides possessed pseudo-two-fold symmetry, despite the lack of two-fold symmetry in the primary sequences, which enabled the tight coupling of the peptide to the receptor, and evidently contributes to guanylyl cyclase activity. The binding of DNP to the NPR-A was essentially identical to that of ANP; however, the affinity of DNP for NPR-A was higher than that of ANP owing to the additional interactions between distinctive sequences in the DNP and NPR-A. Consequently, our findings provide valuable insights that can be applied to the development of novel agonists for the treatment of various human diseases.

Atrial natriuretic peptide T2238C gene polymorphism and the risk of cardiovascular diseases: A meta­analysis.

The present study aimed to investigate the association between atrial natriuretic peptide (ANP) T2238C (rs5065) gene polymorphism and the risk of cardiovascular disease. Relevant literature was obtained by searching databases. The odds ratios (ORs) of the ANP T2238C locus genotype distribution in the case group of cardiovascular diseases and the control group of a non-cardiovascular population were pooled using R software. Sensitivity analysis was used to verify the stability of the results. Egger's linear regression test was used to assess the publication bias of the included literature. Studies were classified according to quality assessment score of the Newcastle-Ottawa scale, year, region, sample size and underlying disease for subgroup analysis, and meta-regression analysis was performed. A total of 12 studies comprising 45,619 patients were included. ANP rs5065 mutant gene C allele was a significant risk factor for myocardial infarction relative to T allele (OR=2.55, 95% CI=1.47-4.43, P=0.0008), CC+CT genotype was a significant risk factor for cerebrovascular events relative to TT (OR=1.14, 95% CI=1.04-1.26, P=0.0048) and the mutant CC genotype was a potential risk factor for the composite cardio-cerebral vascular events (CVE) relative to CT+TT (OR=1.40, 95% CI=0.96-2.04, P=0.081). In studies fulfilling the Hardy-Weinberg equilibrium, the CC genotype was a significant risk factor for the composite CVE relative to TT (OR=2.39, 95% CI=1.40-4.10, P=0.0018) and the CC genotype was a significant risk factor for composite CVE relative to CT+TT (OR=2.41, 95% CI=1.41-4.13, P=0.0015). The P-value of the Egger's test for publication bias was 0.436, which was not statistically significant. The results of the sensitivity analysis were relatively stable. Subgroup analysis indicated that the publication year was a potential source of heterogeneity. Regression analysis was performed for the recessive model in the composite CVE and the results showed that the study region (Europe) was one of the sources of heterogeneity (P=0.016). In conclusion, ANP 2238T/C mutation may increase the risk of myocardial infarction, cerebrovascular events and composite CVE.

MANP in Hypertension With Metabolic Syndrome: Proof-of-Concept Study of Natriuretic Peptide-Based Therapy for Cardiometabolic Disease.

Hypertension and metabolic syndrome frequently coexist to increase the risk for adverse cardiometabolic outcomes. To date, no drug has been proven to be effective in treating hypertension with metabolic syndrome. M-atrial natriuretic peptide is a novel atrial natriuretic peptide analog that activates the particulate guanylyl cyclase A receptor. This study conducted a double-blind, placebo-controlled trial in 22 patients and demonstrated that a single subcutaneous injection of M-atrial natriuretic peptide was safe, well-tolerated, and exerted pleiotropic properties including blood pressure-lowering, lipolytic, and insulin resistance-improving effects. (MANP in Hypertension and Metabolic Syndrome [MANP-HTN-MS]; NCT03781739).

Mass intraoperative endothelial glycocalyx shedding affects postoperative systemic inflammation response.

BACGROUND: Off-pump coronary artery bypass graft (OPCABG) has a high incidence of postoperative systemic inflammation response syndrome (SIRS), and perioperative endothelial glycocalyx layer (EGL) disruption can be one of the predisposing factors. We hypothesized that EGL shedding happened earlier in OPCABG which can influence on postoperative SIRS, and sevoflurane might preserve EGL better than propofol. METHODS: We randomly allocated 50 patients undergoing OPCABG to receive either sevoflurane-sufentanil or propofol-sufentanil anesthesia. Plasma syndecan-1, heparan sulfate (HS), atrial natriuretic peptide (ANP), IL-6, and cardiac troponin I (cTnI) were measured. Blood samples were collected at 6 timepoints: induction (T1), before grafting (T2), after grafting(T3), surgery done (T4), postoperative day1 (POD1,T5) and POD2 (T6). SIRS criteria and sequential organ failure assessment (SOFA) score were examined. RESULTS: There were neither differences of syndecan-1, HS, IL-6 nor of SIRS criteria or SOFA score between the sevoflurane and propofol groups. All patients were pooled as a single group for further statistical analyses, plasma syndecan-1 (P < 0.001) and IL-6 (P < 0.001) increased significantly as a function of time; syndecan-1 increasing correlated significantly with the duration of coronary graft anastomosis (r = 0.329, P = 0.026). Syndecan-1(T3) correlated significantly with ANP(T3) (r = 0.0.354, P = 0.016) and IL-6 (T5) (r = 0.570, P < 0.001). The maximum value of IL-6 correlated significantly with SIRS (r = 0.378, P = 0.010), the maximum value of SOFA score (r = 0.399, P = 0.006) and ICU days (r = 0.306, P = 0.039). The maximum value of SOFA score correlated significantly with the occurrence of SIRS (r = 0.568, P < 0.001) and ICU days (r = 0.338, P = 0.022). CONCLUSIONS: OPCABG intraoperative early EGL shedding caused of grafts anastomosis greatly affected postoperative SIRS and SOFA score, sevoflurane did not clinically preserve EGL better. TRIAL REGISTRATION: ChiCTR-IOR-17012535. Registered on 01/09/2017.

Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Literature Review.

Hospital-acquired pneumonia (HAP) and its subtype, ventilator-associated pneumonia (VAP), remain two significant causes of morbidity and mortality worldwide, despite the better understanding of pathophysiological mechanisms, etiology, risk factors, preventive methods (bundle of care principles) and supportive care. Prior detection of the risk factors combined with a clear clinical judgement based on clinical scores and dosage of different inflammatory biomarkers (procalcitonin, soluble triggering receptor expressed on myelloid cells type 1, C-reactive protein, mid-regional pro-adrenomedullin, mid-regional pro-atrial natriuretic peptide) represent the cornerstones of a well-established management plan by improving patient's outcome. This review article provides an overview of the newly approved terminology considering nosocomial pneumonia, as well as the risk factors, biomarkers, diagnostic methods and new treatment options that can guide the management of this spectrum of infections.

Therapeutic effect of adipose-derived stem cells injected into pericardial cavity in rat heart failure.

AIMS: There are few studies on the treatment of heart failure by injecting stem cells into the pericardial cavity. Can the cells injected into the pericardial cavity migrate through the epicardium to the myocardial tissue? Whether there is therapeutic effect and the mechanism of therapeutic effect are still unclear. This study investigated the therapeutic efficacy and evidence of cell migration of adipose-derived stem cells (ADSCs) injected into the pericardial cavity in rat heart failure. The aim of this study is to demonstrate the effectiveness and mechanism of treating heart failure by injecting stem cells into the pericardial cavity, laying an experimental foundation for a new approach to stem cell therapy for heart disease in clinical practice. METHODS AND RESULTS: The inguinal adipose tissue of male SD rats aged 4-6 weeks was taken, ADSCs were isolated and cultured, and their stem cell surface markers were identified. Forty rats aged 6-8 weeks were divided into sham operation group, heart failure group, and treatment group; there were 15 rats in the heart failure group and 15 rats in the treatment group. The heart failure model was established by intraperitoneal injection of adriamycin hydrochloride. The heart function of the three groups was detected by small animal ultrasound. The model was successful if the left ventricular ejection fraction < 50%. The identified ADSCs were injected into the pericardial cavity of rats in the treatment group. The retention of transplanted cells in pericardial cavity was detected by small animal in vivo imaging instrument, and the migration of transplanted cells into myocardial tissue was observed by tissue section and immunofluorescence. Western blotting and immunohistochemical staining were used to detect brain natriuretic peptide (BNP), α-smooth muscle actin (α-SMA), and C-reactive protein (CRP). ADSCs express CD29, CD44, and CD73. On the fourth day after injection of ADSCs into pericardial cavity, they migrated to myocardial tissue through epicardium and gradually diffused to deep myocardium. The cell density in the pericardial cavity remains at a high level for 10 days after injection and gradually decreases after 10 days. Compared with the heart failure group, the expression of BNP and α-SMA decreased (P < 0.05 and P < 0.001, respectively), and the expression of CRP in the treatment group was higher than that in the heart failure group (P < 0.0001). A small amount of BNP, α-SMA, and CRP was expressed in the myocardium of the sham operation group. After injection of ADSCs, interleukin-6 in myocardial tissue was significantly lower than that in heart failure myocardium (P < 0.01). After treatment, vascular endothelial growth factor A was significantly higher than that of heart failure (P < 0.01). CONCLUSIONS: Pericardial cavity injected ADSCs can penetrate the epicardium, migrate into the myocardium, and have a therapeutic effect on heart failure. Their mechanism of action is to exert therapeutic effects through anti-inflammatory, anti-fibrosis, and increased angiogenesis.

Differential Associations of A-/B-Type Natriuretic Peptides With Cardiac Structure, Function, and Prognosis in Heart Failure.

BACKGROUND: Natriuretic peptide (NP) elevations are prognostic in heart failure (HF), but relative atrial NP deficiency in acute HF has been suggested. OBJECTIVES: The authors compared plasma concentrations and relative strength of associations of A- and B-type NPs with cardiac structure/function and clinical outcomes in HF. METHODS: Midregional pro-atrial natriuretic peptide (MR-proANP), B-type natriuretic peptide (BNP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured in patients with compensated HF in a prospective, multicenter study. The primary outcome was a composite of HF-hospitalization or all-cause mortality. Secondary outcomes included individual primary outcome components and cardiovascular admission. RESULTS: Among 1,278 patients (age 60.1 ± 12.1 years, 82% men, left ventricular ejection fraction [LVEF] 34% ± 14%), median concentrations of MR-proANP were 990 pg/mL (Q1-Q3: 557-1,563 pg/mL), NT-proBNP 1,648 pg/mL (Q1-Q3: 652-3,960 pg/mL), and BNP 291 pg/mL (Q1-Q3: 103-777 pg/mL). No subpopulation with inappropriately low MR-proANP (relative to BNP/NT-proBNP) was observed. Clinical event rates were similar for biomarker tertiles. Increments in MR-proANP exhibited steeper associations with concurrent shifts in left ventricular size, diastolic indexes and LVEF than BNP/NT-proBNP at baseline and serially (P < 0.05), and lower odds of beneficial left ventricular reverse remodeling: OR: 0.35 (95% CI: 0.18-0.70). In single-biomarker models, MR-proANP(log10) was associated with the highest hazard (4 to 6 times) for each outcome. In multimarker models, independent associations were observed for the primary outcome (MR-proANP and NT-proBNP), HF-hospitalization and cardiovascular admission (MR-proANP only), and all-cause mortality (NT-proBNP only) (P < 0.05). The discriminative value of MR-proANP was superior to BNP/NT-proBNP (HF-hospitalization) and BNP (primary outcome) (P < 0.05). CONCLUSIONS: MR-proANP was not inappropriately low relative to concurrent BNP/NT-proBNP values. Proportional increments in MR-proANP were more pronounced than for B-peptides for given decrements in cardiac structure/function. MR-proANP offered greater independent predictive power overall.

Predictors of a Good Diuretic Response and Administration Methods for Carperitide in Patients With Acute Heart Failure.

PURPOSE: In Japan, carperitide has been recommended for the treatment of pulmonary congestion in patients with acute heart failure. Identifying useful indicators to support the decision to administer carperitide and the optimal timing of administration may lead to better improvement of pulmonary congestion. Therefore, we investigated the factors associated with good diuretic response to carperitide in patients with acute heart failure and the optimal timing of carperitide administration. METHODS: This retrospective cohort study investigated 293 hospitalized patients who were diagnosed with acute heart failure and treated with carperitide at the Department of Cardiology, Showa University Fujigaoka Hospital. The primary endpoint was the diuretic response to carperitide. Patients with urine output ≥100 mL/h were defined as the good diuretic response group, and those with a urine output <100 mL/h during the first 6 hours of carperitide administration were defined as the poor diuretic response group. Multivariate analysis was used to examine the predictors of good diuretic response. The relationship between the time from intravenous furosemide to carperitide administration and urine output was also investigated. FINDINGS: The patients' median age was 77 (range: 28-99) years, and 75.5% had New York Heart Association stage IV acute heart failure. The median urine output within 6 hours of carperitide administration was 104.5 (range: 6.6-1571.3) mL/h, and 118 patients (53.6%) showed a good diuretic response. Significant predictors of good diuretic response were age < 75 years [odds ratio (OR) 4.186; 95% confidence interval (CI), 2.129-8.230; P < 0.001], no prior use of loop diuretics (OR 2.155; 95% CI, 1.104-4.207; P = 0.024), blood urea nitrogen <20 mg/dL (OR 2.637; 95% CI, 1.340-5.190; P = 0.005), and white blood cell count <8.6 × 109/L (OR 3.162; 95% CI, 1.628-6.140; P = 0.001). The median urine output in the group with <2 hours between intravenous furosemide and carperitide administration was significantly higher than that in the group with an interval >6 hours [127.3; interquartile range (IQR), 77.6-216.2 mL/h vs. 66.2; IQR. 51.8-114.8 mL/h; P = 0.012). IMPLICATIONS: The 4 predictors (age, no prior use of loop diuretics, blood urea nitrogen, and white blood cell count) of good diuretic response are useful indicators to support decision-making for carperitide administration. Additionally, the administration of carperitide within 2 hours of intravenous furosemide may lead to the improvement of pulmonary congestion.

Effects of low-dose levothyroxine on atrial natriuretic peptide and c-type natriuretic peptide in children with neonatal hypothyroidism.

OBJECTIVE: This study was designed to explore the effects of low-dose levothyroxine (LT4) on levels of atrial natriuretic peptide (ANP) and c-type natriuretic peptide (CNP) in neonates with hypothyroidism (NH). METHODS: In this retrospective study, a total of 90 cases of NH screened out and confirmed by the First Affiliated Hospital of Zhejiang Chinese Medical University from October 2014 to February 2018 were selected as a study group. 80 healthy children who underwent physical examination during the same time period were enrolled as controls. Before and after treatment with LT4, the changes in the levels of serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) were observed, and the changes in the levels of ANP and CNP and their relationships to clinical efficacy were evaluated. Additionally, the growth and development of body and the scores of the China-Wechsler Younger Children Scale of Intelligence (C-WYCSI) were compared before and after the treatment, and the changes in the cardiac functions of children in the study group were evaluated. Independent risk factors for mental abnormality after treatment were analyzed by logistic regression. RESULTS: After treatment, TSH levels in patients declined, while the levels of T3, T4, free triiodothyronine (FT3), and FT4 increased, without significant differences between groups. After treatment, ANP levels in patients increased but CNP levels decreased. ANP levels were negatively correlated with clinical efficacy, but CNP levels were positively correlated with it. Ultrasonic cardiography showed the improved cardiac functions. After treatment, the growth and development of body and the C-WYCSI scores increased compared to those before treatment. First visit date, T3, FT4, TSH were independent risk factors for mental disorders in children. CONCLUSION: For children with NH, low-dose LT4 can correct the level of thyroid function, promote physical and mental development, and improve the levels of ANP and CNP.

Longitudinal Changes in Natriuretic Peptides and Reverse Cardiac Remodeling in Patients with Heart Failure Treated with Sacubitril/Valsartan Across the Left Ventricular Ejection Traction Spectrum.

Sacubitril/valsartan improves outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the relationship between longitudinal changes in natriuretic peptides and echocardiographic parameters in patients with HF treated with sacubitril/valsartan across the left ventricular ejection fraction (LVEF) range is not fully understood.In patients with HF treated with sacubitril/valsartan, comprehensive data on natriuretic peptides, including atrial natriuretic peptide (ANP), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), BNP, and echocardiography, were measured after 6 months of treatment. We assessed the change in natriuretic peptides and echocardiographic parameters in LVEF classification subgroups.Among 49 patients, the median ANP concentration increased from 55 pg/mL at baseline to 78 pg/mL (P < 0.001). The NT-proBNP concentration decreased from 250 pg/mL to 146 pg/mL (P < 0.001). No significant change was observed in the BNP concentration (P = 0.640). The trajectories of each natriuretic peptide in patients with LVEF > 40% (n = 22) were similar to those in individuals with LVEF ≤ 40% (n = 27). Regardless of LVEF classification, echocardiography at 6 months showed a significant improvement in LVEF, left ventricular end-diastolic volume, and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'). The reduction in natriuretic peptide concentration was related to LV reverse remodeling and decreased left and right atrial pressures assessed by E/e' and inferior vena cava diameter.Sacubitril/valsartan induced an increase in ANP, a reduction in NT-proBNP, and no change in plasma BNP, regardless of LVEF. It caused LV reverse remodeling, and the natriuretic peptide concentration changes were associated with structural and functional echocardiographic parameters.

[Effects of moxibustion of "biaoben acupoint combination" on heart rate variability, atrial natriuretic peptide in the model rats of IBS-D complicated with anxiety].

OBJECTIVE: To compare the effects on the heart rate variability (HRV) and the expression of the atrial natriuretic peptide (ANP) in the model rats of irritable bowel syndrome with predominant diarrhea (IBS-D) rats complicated with anxiety between moxibustion of "biaoben acupoint combination" and that of "conventional acupoint combination". METHODS: Of 50 healthy SPF female SD rats, aged 3 months, 8 rats were selected randomly as a blank group, and the rest rats were prepared to be the model of IBS-D complicated with anxiety. Twenty-four rats after successfully modeled were randomized into a model group, a conventional acupoint combination group (convention group) and a biaoben acupoint combination group (biaoben group), 8 rats in each one. In the convention group, moxibustion was delivered at "Tianshu" (ST 25), "Zusanli"(ST 36) and "Shangjuxu"(ST 37); and in the biaoben group, moxibustion was applied to "Neiguan" (PC 6), "Zusanli" (ST 36), and "Guanyuan" (CV 4). One session of moxibustion took 20 min, once daily, for 14 days in total. Before and after intervention, the body mass and fecal moisture content were compared in the rats of each group; using abdominal wall withdrawal reflex, the visceral hypersensitivity was evaluated; with elevated plus maze (EPM) and light-dark box (LDB), the anxiety conditions were assessed. After intervention, HRV was compared among groups, the ultrastructure of intestinal mucosa was observed under the transmission electron microscope in the rats of each group, and ANP expression in the myocardial tissue was detected using Western blot method and immunofluorescence. RESULTS: Before the intervention, compared with the blank group, the body mass and visceral pain threshold of rats were reduced in the model group, the convention group and the biaoben group (P<0.05), fecal moisture content and AWR scores (at the dilatation pressure of 40, 60 and 80 mm Hg, 1 mm Hg ≈ 0.133 kPa) were elevated (P<0.05); and time in the open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). After the intervention, compared with the blank group, in the model group, the body mass, visceral pain threshold, standard diviation of NN intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were dropped (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 40, 60 and 80 mm Hg), LF/HF and ANP expression were increased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). When compared with the model group, in the convention group and the biaoben group, the body mass, visceral pain threshold, SDNN and RMSSD were increased (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 60 and 80 mm Hg), LF/HF and ANP expression were dropped (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). In the biaoben group, compared with the convention group, the body mass, visceral pain threshold, SDNN and RMSSD were elevated (P<0.05), fecal moisture content, AWR score (the dilation pressure of 80 mm Hg), LF/HF and ANP expression were decreased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). The epithelial cells of the intestinal mucosa showed a normal morphology in the blank group, the tight junction of the cells was disrupted and the junction was loose in the model group; the tight junction was imperfect in the convention group, but it was intact in the biaoben group. CONCLUSION: Compared with the conventional acupoint combination, moxibustion of biaoben acupoint combination is more effective on the symptoms of IBS-D complicated with anxiety in the model rats. The effect mechanism may be related to attenuating anxiety-like negative emotions, positively regulating HRV, stabilizing IBS-D intestinal mucosal barrier and down-regulating the expression of ANP in myocardium.

Effects of liraglutide on ANP secretion and cardiac dynamics.

To observe the effects of liraglutide (analog of glucagon-like peptide 1 (GLP-1)) on atrial natriuretic peptide (ANP) secretion and atrial dynamics, an ex vivo isolated rat atrial perfusion model was used to determine atrial ANP secretion and pulse pressure. DPP-4-/- mice were also established in vivo. ANP levels were determined by radioimmunoassay; GLP-1 content was determined by Elisa. The expression levels of GLP-1 receptor (GLP-1R), PI3K/AKT/mTOR, piezo 1, and cathepsin K were analyzed by Western blot. In the clinical study, patients with acute coronary syndrome (ACS) had low levels of plasma GLP-1 but relatively high levels of plasma ANP. In ex vivo (3.2 nmol/L) and in vivo (30 µg/kg) models, liraglutide significantly decreased ANP levels and atrial pulse pressure. Exendin9-39 alone (GLP-1R antagonist) reversibly significantly increased ANP secretion, and the reduction effect of liraglutide on the secretion of ANP was significantly alleviated by Exendin9-39. Exendin9-39 demonstrated slightly decreased atrial pulse pressure; however, combined liraglutide and Exendin9-39 significantly decreased atrial pulse pressure. Ly294002 (PI3K/AKT inhibitor) inhibited the increase of ANP secretion by liraglutide for a short time, while Ly294002 didn't counteract the decrease in pulse pressure by liraglutide in atrial dynamics studies. Liraglutide increased the expression of GLP-1R and PI3K/AKT/mTOR in isolated rat atria and the hearts of mice in vivo, whereas Exendin9-39 reversibly reduced the expression of GLP-1R and PI3K/AKT/mTOR. Piezo 1 was significantly decreased in wild type and DPP-4-/- mouse heart or isolated rat atria after being treated with liraglutide. Cathepsin K expression was only decreased in in vivo model hearts. Liraglutide can inhibit ANP secretion while decreasing atrial pulse pressure mediated by GLP-1R. Liraglutide probably plays a role in the reduction of ANP secretion via the PI3K/AKT/mTOR signaling pathway. Piezo 1 and cathepsin K may be involved in the liraglutide mechanism of reduction.