Human Atrial Natriuretic Peptide Research Articles

A-Type Natriuretic Peptide Alters the Impact of Azithromycin on Planktonic Culture and on (Monospecies and Binary) Biofilms of Skin Bacteria Kytococcus schroeteri and Staphylococcus aureus.

It has been established that the human atrial natriuretic peptide is able to alter the effect of azithromycin on Kytococcus schroeteri H01 and Staphylococcus aureus 209P monospecies and binary biofilms. The effect of the hormone depends on the surface type and cultivation system, and it may have both enhancing and counteracting effects. The antagonistic effect of the hormone was observed mostly on hydrophobic surfaces, whereas the additive effect was observed on hydrophilic surfaces like glass. Also, the effect of the hormone depends on the antibiotic concentration and bacterial species. The combination of azithromycin and ANP led to an amplification of cell aggregation in biofilms, to the potential increase in matrix synthesis, and to a decrease in S. aureus in the binary community. Also, ANP, azithromycin, and their combinations caused the differential expression of genes of resistance to different antibiotics, like macrolides (mostly increasing expression in kytococci), fluoroquinolones, aminoglycosides, and others, in both bacteria.

Unveiling the potential role of natriuretic peptide receptor a isoforms in fine-tuning the cGMP production and tissue-specific function

Atrial natriuretic peptide (ANP) is a peptide hormone that regulates blood pressure and volume. ANP interacts with natriuretic peptide receptor-A (NPR-A) to lower the blood pressure through vasodilation, diuresis and natriuresis. Previously, we designed two human ANP analogues, one with exclusively diuretic function (DGD-ANP) and the other with exclusively vasodilatory function (DRD-ANP). Although both ANP analogues interact with NPR-A, their ability to produce cGMP was different. Three alternatively spliced isoforms of NPR-A were previously identified in rodents. Here, we evaluated the putative human isoforms for their cGMP production independently and in combination with WT NPR-A in various percentages. All three NPR-A isoforms failed to produce cGMP in the presence of ANP, DGD-ANP, or DRD-ANP. Co-expression of isoforms with WT NPR-A were found to significantly impair cGMP production. Considering the differential tissue expression levels of all three spliced isoforms in rodents have previously been demonstrated, the existence of these non-functional receptor isoforms may act as negative regulator for ANP/NPR-A activation and fine-tune cGMP production by WT NPR-A to different degree in different tissues. Thus, NPR-A isoforms potentially contribute to tissue-specific functions of ANP.

Seasonal variation in predialysis systolic blood pressure and cardiovascular events in patients on maintenance hemodialysis.

Predialysis systolic blood pressure (SBP) in patients on hemodialysis (HD) consistently followed a seasonal pattern, reaching a peak in winter and nadir in summer, similar to blood pressure in the general population. However, the relationship between seasonal variations in predialysis SBP and clinical outcomes is still under-investigated in Japanese patients on HD. This retrospective cohort study included 307 Japanese patients undergoing HD for >1 year in three dialysis clinics and evaluated the association between the standard deviation (SD) of predialysis SBP and clinical outcomes, including major adverse cardiovascular events (MACEs; cardiovascular death, nonfatal myocardial infarction or unstable angina, stroke, heart failure, and other severe cardiovascular events requiring hospitalization) with 2.5 years follow-up. The SD of predialysis SBP was 8.2 (6.4-10.9) mmHg. In the model fully adjusted for the SD of predialysis SBP, predialysis SBP, age, sex, HD vintage, Charlson comorbidity index, ultrafiltration rate, renin-angiotensin system inhibitors, corrected calcium, phosphorus, human atrial natriuretic peptide, C-reactive protein, albumin, hemoglobin, body mass index, normalized protein catabolism rate, and intradialytic SBP decline, Cox regression analyses showed that a higher SD of predialysis SBP (per 10 mmHg) was significantly associated with increased MACE risk (hazard ratio [HR], 1.89; 95% confidence interval [95% CI], 1.07-3.36) and all-cause hospitalization (HR, 1.57; 95% CI, 1.07-2.30). Therefore, greater seasonal variations in predialysis SBP were associated with worse clinical outcomes, including MACEs and all-cause hospitalization. Whether interventions to reduce seasonal variations in predialysis SBP will improve the prognosis of Japanese patients on HD must be investigated further.

#5277 THE EVALUATION OF FLUID VOLUME AND PROGNOSIS IN HEMODIALYSIS PATIENTS UTILIZING PLASMA HUMAN ATRIAL NATRIURETIC PEPTIDE

Abstract Background and Aims Volume overload leads to the development of heart failure, which contributes to the high mortality in patients on hemodialysis. The post-dialysis plasma level of human atrial natriuretic peptide (hANP) reflects the fluid volume in patients on hemodialysis. The threshold hANP level is reportedly 100 pg/mL; however, the clinical usefulness of the threshold hANP level for volume control has not been sufficiently studied. Method We conducted a single-center, retrospective, observational study that included 156 hemodialysis patients without atrial fibrillation. First, we examined the usefulness of the threshold hANP level (100 pg/mL) for predicting hypoxemia due to congestion in a short-term observational study from December 30, 2015 to January 5, 2016. Subsequently, we conducted a 5-year follow-up study wherein the outcomes were hospitalization due to acute heart failure (AHF), development of cardiovascular diseases (CVD), and all-cause death. Finally, we collected echocardiography data to investigate the relationship between cardiac function and hANP. Results Our short-term observational study showed that patients with an hANP level ≥ 100 pg/mL developed hypoxemia due to congestion (odds ratio, 3.52; 95% confidence interval, 1.06–11.71; P = 0.040). At the 5-year follow-up, patients with an hANP level ≥ 100 pg/mL had significantly higher rates of hospitalization due to AHF, CVD, and all-cause death based on the log-rank test (P = 0.003, P = 0.019, P < 0.001, respectively). Analysis of echocardiography data showed that the presence of reduced left ventricular ejection fraction and left ventricular diastolic disfunction were significantly associated with high plasma hANP levels. However, the threshold hANP level (100 pg/mL) remained independently associated with hospitalization due to AHF after adjusting for cardiac disfunctions in the multivariable model. Conclusion The hANP level is indicative of both fluid volume and cardiac dysfunction. In clinical practice, we suggest utilizing hANP as an easily accessible measure to identify high-risk patients for developing AHF initially. If the hANP level exceeds 100 mg/dL, we propose to perform echocardiography and consider reducing the DW. In clinical practice, the plasma hANP level could serve as a valuable indicator for assessing the risk of developing AHF and managing fluid volume.

The natriuretic peptide receptor agonist osteocrin disperses Pseudomonas aeruginosa biofilm

Biofilms are highly tolerant to antimicrobials and host immune defense, enabling pathogens to thrive in hostile environments. The diversity of microbial biofilm infections requires alternative and complex treatment strategies. In a previous work we demonstrated that the human Atrial Natriuretic Peptide (hANP) displays a strong anti-biofilm activity toward Pseudomonas aeruginosa and that the binding of hANP by the AmiC protein supports this effect. This AmiC sensor has been identified as an analog of the human natriuretic peptide receptor subtype C (h-NPRC). In the present study, we evaluated the anti-biofilm activity of the h-NPRC agonist, osteocrin (OSTN), a hormone that displays a strong affinity for the AmiC sensor at least in vitro. Using molecular docking, we identified a pocket in the AmiC sensor that OSTN reproducibly docks into, suggesting that OSTN might possess an anti-biofilm activity as well as hANP. This hypothesis was validated since we observed that OSTN dispersed established biofilm of P. aeruginosa PA14 strain at the same concentrations as hANP. However, the OSTN dispersal effect is less marked than that observed for the hANP (−61% versus −73%). We demonstrated that the co-exposure of P. aeruginosa preformed biofilm to hANP and OSTN induced a biofilm dispersion with a similar effect to that observed with hANP alone suggesting a similar mechanism of action of these two peptides. This was confirmed by the observation that OSTN anti-biofilm activity requires the activation of the complex composed by the sensor AmiC and the regulator AmiR of the ami pathway. Using a panel of both P. aeruginosa laboratory reference strains and clinical isolates, we observed that the OSTN capacity to disperse established biofilms is highly variable from one strain to another. Taken together, these results show that similarly to the hANP hormone, OSTN has a strong potential to be used as a tool to disperse P. aeruginosa biofilms.

Reversal of the detrimental effects of social isolation on ischemic cerebral injury and stroke-associated pneumonia by inhibiting small intestinal γδ T-cell migration into the brain and lung

Social isolation (ISO) is associated with an increased risk and poor outcomes of ischemic stroke. However, the roles and mechanisms of ISO in stroke-associated pneumonia (SAP) remain unclear. Adult male mice were single- or pair-housed with an ovariectomized female mouse and then subjected to transient middle cerebral artery occlusion. Isolated mice were treated with the natriuretic peptide receptor A antagonist A71915 or anti-gamma-delta (γδ) TCR monoclonal antibody, whereas pair-housed mice were treated with recombinant human atrial natriuretic peptide (rhANP). Subdiaphragmatic vagotomy (SDV) was performed 14 days before single- or pair-housed conditions. We found that ISO significantly worsened brain and lung injuries relative to pair housing, which was partially mediated by elevated interleukin (IL)-17A levels and the migration of small intestine-derived inflammatory γδ T-cells into the brain and lung. However, rhANP treatment or SDV could ameliorate ISO-exacerbated post-stroke brain and lung damage by reducing IL-17A levels and inhibiting the migration of inflammatory γδ T-cells into the brain and lung. Our results suggest that rhANP mitigated ISO-induced exacerbation of SAP and ischemic cerebral injury by inhibiting small intestine-derived γδ T-cell migration into the lung and brain, which could be mediated by the subdiaphragmatic vagus nerve.

Taipan Natriuretic Peptides Are Potent and Selective Agonists for the Natriuretic Peptide Receptor A.

Cardiovascular ailments are a major cause of mortality where over 1.3 billion people suffer from hypertension leading to heart-disease related deaths. Snake venoms possess a broad repertoire of natriuretic peptides with therapeutic potential for treating hypertension, congestive heart failure, and related cardiovascular disease. We now describe several taipan (Oxyuranus microlepidotus) natriuretic peptides TNPa-e which stimulated cGMP production through the natriuretic peptide receptor A (NPR-A) with higher potencies for the rat NPR-A (rNPR-A) over human NPR-A (hNPR-A). TNPc and TNPd were the most potent, demonstrating 100- and 560-fold selectivity for rNPR-A over hNPR-A. In vivo studies found that TNPc decreased diastolic and systolic blood pressure (BP) and increased heart rate (HR) in conscious normotensive rabbits, to a level that was similar to that of human atrial natriuretic peptide (hANP). TNPc also enhanced the bradycardia due to cardiac afferent stimulation (Bezold-Jarisch reflex). This indicated that TNPc possesses the ability to lower blood pressure and facilitate cardiac vagal afferent reflexes but unlike hANP does not produce tachycardia. The 3-dimensional structure of TNPc was well defined within the pharmacophoric disulfide ring, displaying two turn-like regions (RMSD = 1.15 Å). Further, its much greater biological stability together with its selectivity and potency will enhance its usefulness as a biological tool.

Assessing fluid volume and determining outcomes of acute heart failure using plasma human atrial natriuretic peptide

BackgroundThe post-dialysis plasma level of human atrial natriuretic peptide (hANP) reflects the fluid volume in patients on hemodialysis. The threshold hANP level is reportedly 100 pg/mL; however, the clinical usefulness of the threshold hANP level for volume control has not been sufficiently studied.MethodsWe conducted a single-center, retrospective, observational study that included 156 hemodialysis patients without atrial fibrillation. First, we examined the usefulness of the threshold hANP level (100 pg/mL) for predicting hypoxemia due to congestion in a short-term observational study from December 30, 2015 to January 5, 2016. Subsequently, we conducted a 5-year follow-up study wherein the outcomes were hospitalization due to acute heart failure (AHF), development of cardiovascular diseases (CVD), and all-cause death. Finally, we collected echocardiography data to investigate the relationship between cardiac function and hANP.ResultsOur short-term observational study showed that patients with an hANP level ≥ 100 pg/mL developed hypoxemia due to congestion (odds ratio, 3.52; 95% confidence interval, 1.06–11.71; P = 0.040). At the 5-year follow-up, patients with an hANP level ≥ 100 pg/mL had significantly higher rates of hospitalization due to AHF, CVD, and all-cause death based on the log-rank test (P = 0.003, P = 0.019, P < 0.001, respectively). Cardiac disfunctions were significantly associated with the high hANP level.ConclusionsThe hANP level is indicative of both fluid volume and cardiac dysfunction. A threshold hANP level of 100 pg/mL can serve as a predictive marker for AHF and a practical indicator for volume control.

Association between Intra- and Extra-Cellular Water Ratio Imbalance and Natriuretic Peptides in Patients Undergoing Hemodialysis

Natriuretic peptides are associated with malnutrition and volume overload. Over-hydration cannot simply be explained by excess extracellular water in patients undergoing hemodialysis. We assessed the relationship between the extracellular and intracellular water (ECW/ICW) ratio, N-terminal pro-B-type natriuretic peptide (NT-proBNP), human atrial natriuretic peptide (hANP), and echocardiographic findings. Body composition was examined by segmental multi-frequency bioelectrical impedance analysis in 368 patients undergoing maintenance dialysis (261 men and 107 women; mean age, 65 ± 12 years). Patients with higher ECW/ICW ratio quartiles tended to be older, were on dialysis longer, and had higher post-dialysis blood pressure and lower body mass index, ultrafiltration volume, serum albumin, blood urea nitrogen, and creatinine levels (p < 0.05). The ECW/ICW ratio significantly increased with decreasing ICW, but not with ECW. Patients with a higher ECW/ICW ratio and lower percent fat had significantly higher natriuretic peptide levels. After adjusting for covariates, the ECW/ICW ratio remained an independent associated factor for natriuretic peptides (β = 0.34, p < 0.001 for NT-proBNP and β = 0.40, p < 0.001 for hANP) and the left ventricular mass index (β = 0.20, p = 0.002). The ICW-ECW volume imbalance regulated by decreased cell mass may explain the reserve capacity for fluid accumulation in patients undergoing hemodialysis.

ODP139 Association between serum soluble (pro)renin receptor level and worsening of cardiac function in hemodialysis patients: A prospective observational study

Abstract A total of 258 maintenance HD patients were recruited and serum s(P)RR concentration was measured. Background factors in patients who survived (S group) and patients who died (D group) during the 12-month follow-up period and relationships between serum s(P)RR level and changes in cardiac function during the follow-up period in the S group were investigated. The median serum s(P)RR value at baseline was29.8 ng/ml. Twenty-four patients died during the follow-up period. Cardiothoracic ratio, human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), and E over e-prime were significantly higher in the D group. In the S group, changes in hANP or BNP were significantly greater in the higher serum s(P)RR group than in the lower serum s(P)RR group. High serum s(P)RR level was significantly correlated with changes in BNP, independent of other factors. High serum s(P)RR level was associated with increases in BNP, independent of other risk factors, suggesting that an increased expression of (P)RR may be associated with a progression of heart failure in HD patients and that serum s(P)RR concentration could be used as a biomarker for selecting patients requiring intensive care. Presentation: No date and time listed

VP.59 A single-arm, open-label, multicenter study of tranilast for advanced heart failure in patients with muscular dystrophy

The transient receptor potential cation channel subfamily V member 2 (TRPV2) is a stretch-sensitive calcium channel. Myocytes' damage induces TRPV2 expression on the sarcolemma, which causes calcium influx into the cytoplasm, and triggers degeneration. TRPV2 inhibition was effective in animal models of cardiomyopathy and muscular dystrophy (MD). Our pilot study showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide (BNP) levels in two MD patients with advanced heart failure. Then, we planned a study to evaluate the safety and efficacy of tranilast for heart failure of MD patients. Subjects were MD patients whose serum BNP levels exceeded 100 pg/mL despite receiving standard therapy. Tranilast was administered orally at 100 mg thrice daily. The primary endpoint was the change in log (BNP) (⊿log [BNP]) at 6 months from baseline. The null hypothesis was determined based on a previous carvedilol study that resulted in a mean population ⊿log [BNP] of 0.18. TRPV2 expression on the mononuclear cell (MNC) surface, cardiac events, left ventricular fractional shortening (FS), human atrial natriuretic peptide (hANP), creatine kinase, and pinch strength were also assessed. Because of the poor general condition of many patients, among 18 patients included, 13 patients could be treated according to the protocol throughout the 6-month period. There were no serious adverse events related to tranilast except diarrhea, a known adverse effect. TRPV2 expression on the MNC surface was elevated at baseline and reduced after treatment. BNP, hANP, and FS remained stable. In the per-protocol set group, ⊿log [BNP] was -0.2 and significantly lower than that in the null hypothesis. In conclusion, tranilast is safe and effectively inhibits TRPV2 expression, even in MD patients with advanced heart failure. To evaluate the efficacy of tranilast in preventing heart failure, motor impairment, and respiratory failure, we are planning a study for mild MD patients.

The Correlations of Human Atrial Natriuretic Peptide on Cardiac Function and Hemodynamics in Pediatric Septic Shock.

PurposeWe aimed to determine the correlations of human Atrial Natriuretic Peptide (ANP) on cardiac function and hemodynamics in pediatric septic shock.Patients and MethodsWe conducted an observational and prospective study on 30 children with septic shock. Measurement of the level of human atrial natriuretic peptide was determined in the serum of patients. Cardiac power (CP) is a cardiac function parameter measured with cardiac output (cardiovascular flow) and mean arterial (intravascular) pressure. Cardiac output and mean arterial pressure were monitored using pressure recording analytical methods (PRAM). Hemodynamic status was represented by a vasoactive inotropic score.ResultsThirty pediatric septic shock patients fulfilled the eligibility criteria. The human ANP level was not significantly different in pediatric septic shock on three days of examination. Cardiac power was significantly different in pediatric septic shock on three days of examination. There was a correlation between human ANP and cardiac power on day 3 and human ANP and VIS on day 2.ConclusionThere was a significant correlation between human ANP level and cardiac power on day 3 and ANP level and VIS on day 2. The cardiac power on day 3 and VIS on 48 hours can be alternatives to evaluate the hemodynamic status and cardiac function concerning human ANP in pediatric septic shock.

Tranilast for advanced heart failure in patients with muscular dystrophy: a single-arm, open-label, multicenter study

BackgroundThe transient receptor potential cation channel subfamily V member 2 (TRPV2) is a stretch-sensitive calcium channel. TRPV2 overexpression in the sarcolemma of skeletal and cardiac myocytes causes calcium influx into the cytoplasm, which triggers myocyte degeneration. In animal models of cardiomyopathy and muscular dystrophy (MD), TRPV2 inhibition was effective against heart failure and motor function. Our previous pilot study showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide (BNP) levels in two MD patients with advanced heart failure. Thus, this single-arm, open-label, multicenter study aimed to evaluate the safety and efficacy of tranilast for heart failure.MethodsThe study enrolled MD patients with advanced heart failure whose serum BNP levels were > 100 pg/mL despite receiving standard cardioprotective therapy. Tranilast was administered orally at 100 mg, thrice daily. The primary endpoint was the change in log (BNP) (Δlog [BNP]) at 6 months from baseline. The null hypothesis was determined based on a previous multicenter study of carvedilol results in a mean population Δlog (BNP) of 0.18. TRPV2 expression on peripheral blood mononuclear cell surface, cardiac events, total mortality, left ventricular fractional shortening, human atrial natriuretic peptide, cardiac troponin T, and creatine kinase, and pinch strength were also assessed.ResultsBecause of the poor general condition of many patients, only 18 of 34 patients were included and 13 patients could be treated according to the protocol throughout the 6-month period. However, there were no serious adverse events related to tranilast except diarrhea, a known adverse effect, and the drug was administered safely. TRPV2 expression on the mononuclear cell surface was elevated at baseline and reduced after treatment. Cardiac biomarkers such as BNP, human atrial natriuretic peptide, and fractional shortening remained stable, suggesting a protective effect against the progression of heart failure. In the per protocol set group, Δlog [BNP] was − 0.2 and significantly lower than that in the null hypothesis.ConclusionsTranilast is safe and effective in inhibiting TRPV2 expression, even in MD patients with advanced heart failure. Further trials are needed to evaluate the efficacy of tranilast in preventing myocardial damage, heart failure, motor impairment, and respiratory failure.Clinical trial registration The study was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000031965, URL: http://www.umin.ac.jp/ctr/) [March 30, 2018] and the Japan Registry of Clinical Trials (jRCT, registration number: jRCTs031180038, URL: https://jrct.niph.go.jp/) [November 12, 2021]. Patient registration was started in December 19, 2018.

Pseudomonas aeruginosa Biofilm Dispersion by the Human Atrial Natriuretic Peptide.

Pseudomonas aeruginosa biofilms cause chronic, antibiotic tolerant infections in wounds and lungs. Numerous recent studies demonstrate that bacteria can detect human communication compounds through specific sensor/receptor tools that modulate bacterial physiology. Consequently, interfering with these mechanisms offers an exciting opportunity to directly affect the infection process. It is shown that the human hormone Atrial Natriuretic Peptide (hANP) both prevents the formation of P. aeruginosa biofilms and strongly disperses established P. aeruginosa biofilms. This hANP action is dose‐dependent with a strong effect at low nanomolar concentrations and takes effect in 30–120 min. Furthermore, although hANP has no antimicrobial effect, it acts as an antibiotic adjuvant. hANP enhances the antibiofilm action of antibiotics with diverse modes of action, allowing almost full biofilm eradication. The hANP effect requires the presence of the P. aeruginosa sensor AmiC and the AmiR antiterminator regulator, indicating a specific mode of action. These data establish the activation of the ami pathway as a potential mechanism for P. aeruginosa biofilm dispersion. hANP appears to be devoid of toxicity, does not enhance bacterial pathogenicity, and acts synergistically with antibiotics. These data show that hANP is a promising powerful antibiofilm weapon against established P. aeruginosa biofilms in chronic infections.

Role of the new bioimpedance monitoring device (Seca®) in assessing dry weight in hemodialysis patients.

In recent years, bioimpedance analysis has come to be widely used in clinical practice for dialysis patients, but there is not sufficient consensus on its significance. We aimed to examine the merits of performing bioimpedance analysis in addition to conventional evaluation methods for dry weight such as measuring human atrial natriuretic peptide (hANP), blood pressure, and cardiothoracic ratio in patients on chronic hemodialysis. Body composition of 78 hemodialysis patients was performed by using a new and more accurate segmental multifrequency bioimpedance analysis device (Seca® medical body composition analyzer 525, Seca GmbH & Co. KG, Hamburg, Germany). Laboratory data including hANP at post-dialysis and demographic profile were collected. Statistical analysis was performed with SPSS software. Mean age of the patients was 66.9 ± 12.6years and 80.8% were males. Mean value of hANP and the ratio of extracellular water to total body water (ECW/TBW) were 61.4 ± 36.4pg/mL and 46.1 ± 3.9%, respectively. The calculated ECW/TBW cutoff point for hANP > 50pg/mL was 45.0%, with sensitivity of 74.4% and specificity of 64.7%. Patients with an ECW/TBW of more than 45% and hANP value of > 50pg/mL had a higher blood pressure and cardiothoracic ratio on chest X-ray examination. Our results suggest that the ratio of extracellular water to total body water of more than 45% and hANP value of ≥ 50pg/mL were overhydrated in chronic hemodialysis patients. Whether monitoring levels of these parameters has a role in the outcome including patients' survival and cardiovascular events requires further study.

Arabidopsis thaliana Plant Natriuretic Peptide Active Domain Forms Amyloid-like Fibrils in a pH-Dependent Manner.

Plant natriuretic peptides (PNPs) are hormones that have been extracted from many different species, with the Arabidopsis thaliana PNP (AtPNP-A) being the most studied among them. AtPNP-A is a signaling molecule that consists of 130 residues and is secreted into the apoplast, under conditions of biotic or abiotic stress. AtPNP-A has distant sequence homology with human ANP, a protein that forms amyloid fibrils in vivo. In this work, we investigated the amyloidogenic properties of a 34-residue-long peptide, located within the AtPNP-A sequence, in three different pH conditions, using transmission electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy, Congo red and Thioflavin T staining assays. We also utilize bioinformatics tools to study its association with known plant amyloidogenic proteins and other A. thaliana proteins. Our results reveal a new case of a pH-dependent amyloid forming peptide in A. thaliana, with a potential functional role.

Experience Verification of 63 Cases of Liver Transplantation Anesthesia Management

Background: We reviewed the intraoperative management of previous liver transplantation (LT) cases to identify an optimal anesthetic method, which may affect patient outcomes and lead to faster postoperative recovery for future recipients. Methods: This single-center retrospective study reviewed 63 patients who underwent LT, including 51 living donor LT (LDLT), seven deceased donor LT (DDLT), and five simultaneous liver-kidney transplantation patients. We examined the patients’ backgrounds, intraoperative management (anesthetic method, water balance, and catecholamine dosage), and postoperative courses (hospitalization period, length of intensive care unit stay, renal function). Results: All patients received general anesthesia using inhalational anesthetics, either sevoflurane or desflurane, and both drugs were administered similarly. Rocuronium was administered at its usual dose despite liver failure. All patients undergoing preoperative dialysis due to acute kidney injury were successfully withdrawn from dialysis after surgery. The albumin infusion volume was 32% of the total infusion and transfusion volume. The five-year survival rate was 88% and graft failure occurred in one case. Conclusion: The anesthetic management of LT is currently conducted empirically in our institution, and we could not identify an optimal anesthetic method. However, we drew some conclusions. First, the use of human atrial natriuretic peptide as a drug infusion and appropriate transfusion management was expected to restore renal function. Second, the infusion volume of albumin was high. Third, the usual dose of rocuronium was required because excessive bleeding may cause unstable plasma drug concentration. Our results will be useful in future multi-institutional studies or meta-analyses and further improving the outcomes of future transplant recipients.

Serum syndecan-1 concentration in hospitalized patients with heart failure may predict readmission-free survival.

Syndecan-1 is found in the endothelial glycocalyx and is released into the bloodstream during stressed conditions, including severe diseases such as acute kidney injury, chronic kidney disease, and cardiovascular disease. This study investigated the prognostic value of serum syndecan-1 concentration in patients with heart failure upon admission. Serum syndecan-1 concentration was analyzed in 152 patients who were hospitalized for worsening heart failure from September 2017 to June 2018. The primary outcome of the study was readmission-free survival, defined as the time from the first admission to readmission for worsened heart failure or death from any cause, which was assessed at 30 months after discharge from the hospital. The secondary outcome of the study was survival time. Blood samples and echocardiogram data were analyzed. Univariate and multivariable time-dependent Cox regression analyses adjusted for age, creatinine levels, and use of antibiotics were conducted. The serum syndecan-1 concentration was significantly associated with readmission-free survival. Subsequently, the syndecan-1 concentration may have gradually decreased with treatment. The administration of human atrial natriuretic peptide and antibiotics may have modified the relationship between readmission-free survival and serum syndecan-1 concentration (p = 0.01 and 0.008, respectively). Serum syndecan-1 concentrations, which may indicate injury to the endothelial glycocalyx, predict readmission-free survival in patients with heart failure.

RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota\u2013brain axis

BackgroundAtrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment.MethodsLPS (5 mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0 mg/kg) was injected intravenously 24 h before and/or 10 min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14 days before LPS injection or 28 days before fecal microbiota transplantation (FMT). ANA-12 (0.5 mg/kg) was administrated intraperitoneally 30 min prior to rhANP treatment.ResultsLPS (5.0 mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24 h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment.ConclusionsOur results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis.

Inhibitors of Neutral Peptidase

There are several circulated hormones that control intravascular blood volume which are secreted from cardiac tissue, such as atrial natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP). These peptides will be elevated in case of heart failure (HF), and because of their diuretic, natriuretic, vasodilating effects as well as suppressing renin production they will work as compensated for HF. The natriuretic peptides system has critical effect against renin – angiotensin – aldosterone system (RAAS). A suggested therapeutic approach was discussed in HF treatment via performing human recombinant ANP and BNP, but it’s requiring more clinical trials to evaluate the quality of this approach compared to conventional treatment.