Acute myocardial infarction therapy: in vitro and in vivo evaluation of atrial natriuretic peptide and triphenylphosphonium dual ligands modified, baicalin-loaded nanoparticulate system.

BACKGROUND: Myocardial infarction (MI) is one of the most common ischemic heart diseases. It is very essential to explore new types of cardioprotective drugs delivery systems in this area. OBJECTIVE: The aim of the present study was to investigate the protective effect of baicalin (BA) and puerarin (PU) against acute MI rat models. BA and PU co-loaded nanoparticulate system were developed to improve bioavailability of the drugs, to prolong retention time in vivo and to enhance the protective effect. METHODS: In the present study, ANP and TPP contained ligands were synthesized. ANP/TPP-BN-LPNs were prepared and its physico-chemical properties were evaluated. The MI therapy efficiency of ANP/TPP-BN-LPNs was assessed in rats after intravenous injection. Single ligand contained LPNs, no ligand contained LPNs, and BN solution formulations were also prepared and used for the comparison. RESULTS: ANP/TPP-BN-LPNs were uniform and spheroidal particles. The size of ANP/TPP-BN-LPNs was 98.5 ± 2.9 nm, with a zeta potential of -19.5 ± 1.9 mV. The dual ligands modified LPNs exhibited significantly improved therapeutic efficiency compared with the single ligand modified LPNs and other systems. In vivo infarct therapy studies in rats proved that ANP/TPP-BN-LPNs were a promising system for efficient delivery of cardiovascular drugs for the treatment of cardiovascular diseases. CONCLUSIONS: ANP/TPP-BN-LPNs could be used as a long-circulating and heart-targeting drug delivery system.

First-in-Human Study of MANP: A Novel ANP (Atrial Natriuretic Peptide) Analog in Human Hypertension.

[Figure: see text].

Phase I Study of the Administration of Low-dose Perioperative Human Atrial Natriuretic Peptide in Patients With Resectable Colorectal Cancer.

BACKGROUND/AIM: The aim of this single center, non-randomized, open-label, uncontrolled, interventional trial was to determine the feasibility of continuous administration of low-dose human atrial natriuretic peptide (hANP) perioperatively during curative operation for colorectal cancer patients without history of acute heart failure. PATIENTS AND METHODS: The study included three males and two females ranging from 27 to 70 years old. Continuous intravenous injection of hANP solution was started before surgery. The primary endpoint was safety of hANP administration, and the secondary endpoints were perioperative changes in ANP, b-type natriuretic peptide, electrocardiogram (ECG), and lung function. RESULTS: The American Society of Anaesthesiologists physical status was 1, 2, and 3 in three, one, and one patient, respectively. Grade 2 hypotension was observed in one case. No marked changes were observed between pre- and post-operation in all cases. CONCLUSION: Perioperative low-dose hANP administration is feasible and safe in patients with curative colorectal cancer.

Effect of low-dose atrial natriuretic peptide in critically ill patients with acute kidney injury: a retrospective, single-center study with propensity-score matching.

BACKGROUND: Acute kidney injury (AKI) is a major comorbidity in critically ill patients. Low-dose atrial natriuretic peptide (ANP) has been shown to effectively prevent acute kidney injury (AKI), especially in cardiovascular surgery patients. However, its treatment effects for AKI in critically ill patients are unclear. METHODS: This single-center, retrospective, observational study included patients with AKI diagnosed within 7 days after intensive care unit (ICU) admission during the period January 2010 to December 2017. We conducted a propensity-matched analysis to estimate the treatment effect of low-dose carperitide (a recombinant human ANP) on the clinical outcomes. The primary outcome was a composite of death, renal replacement therapy dependence, or no recovery from AKI (defined as an increase of the serum creatinine level to ≥200% of baseline) at hospital discharge. RESULTS: During the study period, 4479 adult patients were admitted to the ICU. We identified 1374 eligible patients with AKI diagnosed within 7 days after ICU admission. Among these patients, 346 (25.2%) were treated with low-dose carperitide, with an average dose of 0.019 µg kg- 1 min- 1. The primary outcome occurred more often in the treatment group than in the control group (29.7% versus 23.4%, respectively; p = 0.022). After propensity score matching, characteristics of 314 patients from each group were well- balanced. Significant difference of the primary outcome, as seen with the full cohort, was no longer obtained; no benefit of carperitide was detected in the matched cohort (29.0% versus 25.2%; p = 0.281). CONCLUSIONS: Low-dose ANP showed no treatment effect in general critically ill patients who developed AKI.

Predictors of responders for low-dose carperitide monotherapy in patients with acute heart failure.

Human atrial natriuretic peptide, known as carperitide, is approved for early relief of dyspnea in patients with acute heart failure (AHF). However, the diuretic effect of carperitide is sometimes insufficient for controlling volume overload. We investigated predictors for the carperitide response in patients with AHF. Forty-seven patients (age: 74 ± 10 years; left ventricular ejection fraction: 42.0% ± 15.9%) with AHF were enrolled and treated with carperitide monotherapy at a dose of 0.0125 µg/kg/min. Patients without sufficient diuresis (< 60 ml/h) or improvement of symptoms by 4 h after carperitide administration, despite increasing to twice the dose of carperitide and adding another agent, were defined as non-responders. Twenty-four (51%) patients were defined as responders and treated with low-dose carperitide monotherapy on the first day. Multiple logistic regression analysis showed that the response to carperitide monotherapy was independently predicted by serum creatinine levels and systolic blood pressure (SBP) on admission. The area under the receiver-operating characteristic curve for predicting the response to carperitide by SBP was 0.808 (95% confidence interval [0.686-0.930], sensitivity: 83.3%, specificity: 65.2%, cutoff value: 135 mmHg). Four (8.5%) patients developed asymptomatic transient hypotension. Worsening renal function occurred within 3 days of admission in three (6.4%) patients who received low-dose carperitide therapy. SBP and serum creatinine levels on admission might be useful for predicting the diuretic response to low-dose carperitide monotherapy in patients with AHF. Initial use of low-dose carperitide therapy does not have adverse effects on renal function.

Hormonal regulation of thirst in the amphibious ray-finned fish suggests the requirement for terrestrialization during evolution.

Thirst has evolved for vertebrate terrestrial adaptation. We previously showed that buccal drying induced a series of drinking behaviours (migration to water-taking water into the mouth-swallowing) in the amphibious mudskipper goby, thereby discovering thirst in ray-finned fish. However, roles of dipsogenic/antidipsogenic hormones, which act on the thirst center in terrestrial tetrapods, have remained unclear in the mudskipper thirst. Here we examined the hormonal effects on the mudskipper drinking behaviours, particularly the antagonistic interaction between angiotensin II (AngII) and atrial natriuretic peptide (ANP) which is important for thirst regulation in mammalian 'forebrain'. Expectedly, intracerebroventricular injection of ANP in mudskippers reduced AngII-increased drinking rate. ANP also suppressed the neural activity at the 'hindbrain' region for the swallowing reflex, and the maintenance of buccopharyngeal water due to the swallowing inhibition may attenuate the motivation to move to water. Thus, the hormonal molecules involved in drinking regulation, as well as the influence of buccopharyngeal water, appear to be conserved in distantly related species to solve osmoregulatory problems, whereas hormonal control of thirst at the forebrain might have been acquired only in tetrapod lineage during evolution.

Rosiglitazone treatment restores renal responsiveness to atrial natriuretic peptide in rats with congestive heart failure.

The thiazolidinedione (TZD) class of Peroxisome proliferator-activated receptor gamma agonists has restricted clinical use for diabetes mellitus due to fluid retention and potential cardiovascular risks. These side effects are attributed in part to direct salt-retaining effect of TZDs at the renal collecting duct. A recent study from our group revealed that prolonged rosiglitazone (RGZ) treatment caused no Na+/H2 O retention or up-regulation of Na+ transport-linked channels/transporters in experimental congestive heart failure (CHF) induced by surgical aorto-caval fistula (ACF). The present study examines the effects of RGZ on renal and cardiac responses to atrial natriuretic peptide (ANP), Acetylcholine (Ach) and S-Nitroso-N-acetylpenicillamine (SNAP-NO donor). Furthermore, we assessed the impact of RGZ on gene expression related to the ANP signalling pathway in animals with ACF. Rats subjected to ACF (or sham) were treated with either RGZ (30 mg/kg/day) or vehicle for 4 weeks. Cardiac chambers pressures and volumes were assessed invasively via Miller catheter. Kidney excretory and renal hemodynamic in response to ANP, Ach and SNAP were examined. Renal clearance along with cyclic guanosine monophosphate (cGMP), gene expression of renal CHF-related genes and ANP signalling in the kidney were determined. RGZ-treated CHF rats exhibited significant improvement in the natriuretic responses to ANP infusion. This 'sensitization' to ANP was not associated with increases in neither urinary cGMP nor in vitro cGMP production. However, RGZ caused down-regulation of several genes in the renal cortex (Ace, Nos3 and Npr1) and up-regulation of ACE2, Agtrla, Mme and Cftr along down-regulation of Avpr2, Npr1,2, Nos3 and Pde3 in the medulla. In conclusion, CHF+RGZ rats exhibited significant enhancement in the natriuretic responses to ANP infusion, which are known to be blunted in CHF. This 'sensitization' to ANP is independent of cGMP signalling, yet may involve post-cGMP signalling target genes such as ACE2, CFTR and V2 receptor. The possibility that TZD treatment in uncomplicated CHF may be less detrimental than thought before deserves additional investigations.

Effect of intravenous carperitide versus nitrates as first-line vasodilators on in-hospital outcomes in hospitalized patients with acute heart failure: Insight from a nationwide claim-based database.

BACKGROUNDS: Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide. Despite of negative impacts of nesiritide on clinical outcomes for acute heart failure (AHF), carperitide has been used for around a half of Japanese AHF patients as a vasodilator based on limited evidences. We sought to determine the effect of carperitide compared to nitrates in the early care for AHF patients treated with vasodilators. METHODS AND RESULTS: We conducted a cohort study of patients admitted with AHF to 808 hospitals from April 2012 to March 2014. Patients were extracted from 1,422,703 hospitalizations according to ICD-10 heart failure codes. Patients who had sepsis or mechanical supports during hospitalization were excluded. Outcomes were in-hospital death, length of hospitalization and cost of hospitalization. Among 76,924 patients, 45,595 were in patients treated with either carperitide or nitrates during the first 2 days (carperitide; 33,386, nitrates; 12,209). After application of inverse probability of treatment weighting with variables including demographics, comorbidities and treatments, there was perfect balance in both groups. Patients who were treated with carperitide had substantially higher covariate adjusted in-hospital mortality (HR 1.49 95%CI 1.35-1.64), longer length of hospitalization (Coefficients 0.062 95%CI 0.048 to 0.076) and greater cost of hospitalization (Coefficients 0.024 95%CI 0.010 to 0.037) compared to those treated with nitrates. CONCLUSIONS: In Japanese AHF patients during their early inpatient care, carperitide use was significantly associated with worse outcomes when compared to nitrates use, suggesting the routine use of carperitide might not be recommended as a first-line vasodilator for AHF.

High doses of ANP and BNP exacerbate lipolysis in humans and the lipolytic effect of BNP is associated with cardiac triglyceride content in pigs.

Drugs facilitating the cardioprotective effects of natriuretic peptides are introduced in heart failure treatment. ANP and BNP also stimulate lipolysis and increase circulating concentrations of free fatty acids (FFAs); an aspect, however, thought to be confined to primates. We examined the lipolytic effect of natriuretic peptide infusion in healthy young men and evaluated the effect in a porcine model of myocardial ischemia and reperfusion. Six young healthy normotensive men underwent infusion with ANP, BNP, or CNP for 20 min. Blood samples were collected before, during, and after infusion for measurement of FFAs. In a porcine model of myocardial ischemia and reperfusion, animals were infused for 3 h with either BNP (n = 7) or saline (n = 5). Blood samples were collected throughout the infusion period, and cardiac tissue was obtained after infusion for lipid analysis. In humans, ANP infusion dose-dependently increased the FFA concentration in plasma 2.5-10-fold (baseline vs. 0.05 µg/kg/min P < 0.002) and with BNP 1.6-3.5-fold (P = 0.001, baseline vs. 0.02 µg/kg/min) 30 min after initiation of infusion. Infusion of CNP did not affect plasma FFA. In pigs, BNP infusion induced a 3.5-fold increase in plasma FFA (P < 0.0001), which remained elevated throughout the infusion period. Triglyceride content in porcine right cardiac ventricle tissue increased ∼5.5 fold in animals infused with BNP (P = 0.02). Natriuretic peptide infusion has similar lipolytic activity in human and pig. Our data suggest that short-term infusion increases the cardiac lipid content, and that the pig is a suitable model for studies of long-term effects mediated by natriuretic peptides.

Randomized double-blind clinical studies of ularitide and other vasoactive substances in acute decompensated heart failure: a systematic review and meta-analysis.

AIMS: Acute decompensated heart failure (ADHF) has a poor prognosis and limited treatment options. No direct comparisons between ularitide-a synthetic natriuretic peptide being evaluated in ADHF-and other vasoactive substances are available. The aim of this meta-analysis was to determine haemodynamic effect sizes from randomized double-blind trials in ADHF. METHODS AND RESULTS: Eligible studies enrolled patients with ADHF requiring hospitalization and haemodynamic monitoring. Patients received 24-48 h of infusion with a vasoactive substance or comparator. Primary outcome measure was pulmonary artery wedge pressure (PAWP). Treatment effects were quantified as changes from baseline using mean differences between study drug and comparator. Results were analysed using random-effects (primary analysis) and fixed-effects meta-analyses. Twelve randomized, double-blind studies were identified with data after 3, 6, and 24 h of treatment (n = 622, 644, and 644, respectively). At 6 h, significant PAWP benefits for ularitide over placebo were seen (Hedges' g effect size, -0.979; P < 0.0001). On meta-analysis, treatment difference between ularitide and pooled other agents was statistically significant (-0.501; P = 0.0303). Effect sizes were numerically higher with ularitide than other treatments at 3 and 24 h. After 6 h, a significant difference in effect size between ularitide and all other treatments was observed for right atrial pressure (Hedges' g, -0.797 for ularitide and -0.304 for other treatments; P = 0.0274). CONCLUSIONS: After 6 h, ularitide demonstrated high effect sizes for PAWP and right atrial pressure. Improvements in these parameters were greater with ularitide vs. pooled data for other vasoactive drugs.

Effects of early diuretic response to carperitide in acute decompensated heart failure treatment: A single-center retrospective study.

BACKGROUND: Diuretic response is a strong predictor of outcome for admitted patients of acute decompensated heart failure (ADHF). However, little is known about the effects of early diuretic response to carperitide. METHODS: We retrospectively analyzed records of 85 patients hospitalized for ADHF who received carperitide as initial treatment and <40 mg furosemide during the early period. The eligible patients were divided into good diuretic responder (GR) group and poor diuretic responder (PR) group on the basis of median urinary volume. RESULTS: The PR group demonstrated older age, lower body mass index (BMI), lower estimated glomerular filtration rate, and higher blood urea nitrogen (BUN) level, left ventricular ejection fraction, and ß-blockers prescribed at baseline than the GR group. The incidence of worsening renal function (WRF) was significantly higher in the PR group than in the GR group. There was no correlation between early intravenous furosemide dose and urinary volume (Spearman correlation, ρ = 0.111, p = 0.312). Multivariate analysis showed that the statistically significant independent factors associated with poor diuretic response to carperitide were BMI (Odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.68-0.94, p = 0.004) and BUN (OR = 1.07, 95%CI 1.01-1.15, p = 0.018). Kaplan-Meier analysis indicated a lower event-free rate in the PR group than in the GR group (log-rank, p = 0.007). CONCLUSIONS: BMI and BUN levels on admission were significant determinants of early poor diuretic response to carperitide. Early poor diuretic response to carperitide was associated with future poor outcomes.

Guanylyl Cyclase A in Both Renal Proximal Tubular and Vascular Endothelial Cells Protects the Kidney against Acute Injury in Rodent Experimental Endotoxemia Models.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Natriuretic peptides are used, based on empirical observations, in intensive care units as antioliguric treatments. We hypothesized that natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A, a receptor for natriuretic peptides, in proximal tubules and endothelial cells. METHODS: Normal Sprague-Dawley rats and mice lacking guanylyl cyclase A in either endothelial cells or proximal tubular cells were challenged with lipopolysaccharide and assessed for oliguria and intratubular flow rate by intravital imaging with multiphoton microscopy. RESULTS: Recombinant atrial natriuretic peptide efficiently improved urine volume without changing blood pressure after lipopolysaccharide challenge in rats (urine volume at 4 h, lipopolysaccharide: 0.6 ± 0.3 ml · kg · h; lipopolysaccharide + fluid resuscitation: 4.6 ± 2.0 ml · kg · h; lipopolysaccharide + fluid resuscitation + atrial natriuretic peptide: 9.0 ± 4.8 ml · kg · h; mean ± SD; n = 5 per group). Lipopolysaccharide decreased glomerular filtration rate and slowed intraproximal tubular flow rate, as measured by in vivo imaging. Fluid resuscitation restored glomerular filtration rate but not tubular flow rate. Adding atrial natriuretic peptide to fluid resuscitation improved both glomerular filtration rate and tubular flow rate. Mice lacking guanylyl cyclase A in either proximal tubules or endothelium demonstrated less improvement of tubular flow rate when treated with atrial natriuretic peptide, compared with control mice. Deletion of endothelial, but not proximal tubular, guanylyl cyclase A augmented the reduction of glomerular filtration rate by lipopolysaccharide. CONCLUSIONS: Both endogenous and exogenous natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A in proximal tubules and endothelial cells.

Rationale and Design of Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF).

BACKGROUNDS: Despite current therapies, acute heart failure (AHF) remains a major public health burden with high rates of in-hospital and post-discharge morbidity and mortality. Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide that promotes vasodilation with increased salt and water excretion, which leads to reduction of cardiac filling pressures. A previous open-label randomized controlled study showed that carperitide improved long-term cardiovascular mortality and heart failure (HF) hospitalization for patients with AHF, when adding to standard therapy. However, the study was underpowered to detect a difference in mortality because of the small sample size. METHODS: Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF) is a multicenter, randomized, open-label, controlled study designed to evaluate the efficacy of intravenous carperitide in hospitalized patients with AHF. Patients hospitalized for AHF will be randomly assigned to receive either intravenous carperitide (0.02 µg/kg/min) in addition to standard treatment or matching standard treatment for 72 h. The primary end point is death or rehospitalization for HF within 2 years. A total of 260 patients will be enrolled between 2013 and 2018. CONCLUSION: The design of LASCAR-AHF will provide data of whether carperitide reduces the risk of mortality and rehospitalization for HF in selected patients with AHF.

A potent and selective natriuretic peptide receptor-3 blocker 11-mer peptide created by hybridization of musclin and atrial natriuretic peptide.

The natriuretic peptide (NP) system is a critical endocrine, autocrine, and paracrine system and has been investigated for potential use against cardiovascular and metabolic diseases. The clearance of NPs is regulated by the proteolysis of neutral endopeptidase (NEP) and by endocytosis via natriuretic peptide receptor-3 (NPR3). A linear NPR3-selective peptide, [Cha8]-ANP(7-16)-NH2 (1), showed potent binding affinity for NPR3 but poor predicted chemical stability due to its free thiol group. A 12-mer peptide (9) without a thiol group was designed by the hybridization of two NPR3-binding peptides: a linear ANP fragment peptide analog and musclin, a murine member of the bHLH family of transcription factors, possessed high binding affinity and strict selectivity for NPR3. To increase the proteolytic resistance of 9, amino acid substitutions at the cleavage sites led to hydroxyacetyl-[d-Phe5,d-Hyp7,Cha8,d-Ser9,Hyp11,Arg(Me)14]-ANP(5-15)-NHCH3 (23), showing high and selective binding affinity for NPR3 over NPR1 and excellent stability in mouse serum. Compound 23 increased intracellular cGMP concentrations in primary cultured adipocytes, and continuous administration induced substantial plasma cGMP elevation in mice, suggesting its potential to clarify the physiological role of NPR3 and its therapeutic application.

The impact of carperitide usage on the cost of hospitalization and outcome in patients with acute heart failure: High value care vs. low value care campaign in Japan.

BACKGROUND: The usefulness of carperitide in patients with acute heart failure (AHF) has not been confirmed; carperitide is expensive, and thus, its routine use has not been shown to add much value in clinical settings. We analyzed the impact of carperitide usage on the outcome and cost of hospitalization in AHF patients. METHODS: Data obtained from the Diagnosis Procedure Combination (DPC) database from July 2014 until June 2015 from 371 hospitals were analyzed. Emergent patients with acute heart failure (ICD code I50* and DPC code 050130) who did not undergo any surgical procedures were enrolled. We compared the outcomes and cost between the carperitide group and non-carperitide group using propensity score matched analysis. RESULTS: In 37,891 heart failure patients (52.2% male; 79.2±11.9years), 13,421 pairs were selected according to the propensity score matching. In-hospital death occurred more frequently in the carperitide group (n=997; 7.4%) than in the non-carperitide group (n=844; 6.3%; p<0.01). Carperitide use was also related with higher costs of hospitalizations, and total dose of carperitide administered during hospitalization decreased with the increasing case volume (p<0.01). On the other hand, carperitide usage was frequently recognized in hospitals with larger annual case volumes (32.1%, Q1; 37.3%, Q2; 40.7%, Q3, p-value<0.01). CONCLUSIONS: Carperitide usage negatively affected patient outcomes and cost of hospitalization. In hospitals with lower annual case volume, clinicians should pay attention to the total dose and duration of carperitide. On the other hand, in hospitals with larger annual case volumes, clinicians should pay attention to the thresholds/indications to prescribe carperitide in AHF patients.

A multicenter randomized controlled trial of surgery alone or surgery with atrial natriuretic peptide in lung cancer surgery: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative cancer recurrence is a major problem following curative surgery. In a previous retrospective study of lung cancer surgery, we reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduced postoperative recurrence. We demonstrated that ANP inhibited the adhesion of cancer cells to vascular endothelium as a vasoprotective action. The objective of this study is to evaluate the effects of ANP on the incidence of postoperative cancer recurrence in lung cancer surgery. METHODS/DESIGN: The present study is a multicenter, randomized trial with two parallel groups of patients with lung cancer comparing surgery alone and surgery with ANP administration for 3 days during the perioperative period. A total of 500 patients will be enrolled from 10 Japanese institutions. The primary endpoint is 2-year relapse-free survival (RFS). The secondary endpoints are 2-year cancer-specific RFS, 5-year RFS, overall survival, the incidence of postoperative complications, and the completion rate of ANP treatment. DISCUSSION: The principal question addressed in this trial is whether ANP with its vasoprotective action can reduce cancer recurrence following lung cancer surgery. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000018480 . Registered on 31 July 2015.

Low-dose carperitide (α-human A-type natriuretic peptide) alleviates hemoglobin concentration decrease during prolonged oral surgery: a randomized controlled study.

PURPOSE: Surgical injury stimulates the renin-angiotensin-aldosterone system (RAAS) and causes antidiuresis, leading to postoperative oliguria. Carperitide (α-human A-type natriuretic peptide) is a cardiac peptide hormone secreted from the atrium. This peptide hormone enhances diuresis by suppressing the RAAS. In our experience, carperitide alleviates decreased hemoglobin (Hb) concentration during elective surgery. In the current study, we investigated the relationship between low-dose carperitide (0.01 µg/kg/min) and Hb concentration during oral surgery. METHODS: Patients (ASA-PS: I-II, 40-80 years old) undergoing oral maxillofacial surgery (duration of operation >8 h) were enrolled in this study. Patients were divided into two groups: the carperitide group received carperitide at 0.01 µg/kg/min and the control group received normal saline. Body fluid water [including total body water (TBW), extracellular water (ECW), and intracellular water (ICW)], urine volume, and chemical parameters such as Hb concentration, PaO2, and serum electrolytes were evaluated every 2 h. RESULTS: In the carperitide group (n = 15), Hb decreased from 12.6 ± 1.1 to 10.8 ± 1.5 g/dl, while it decreased from 12.6 ± 1.4 to 9.5 ± 1.3 g/dl in the control group (n = 15) (p < 0.05). Urine volume (2557.3 ± 983.5 mL) in the carperitide group was significantly more than it was in the control group (1108.8 ± 586.4 mL; p < 0.001). There were no significant differences in clinical characteristics, body fluid water, PaO2, and serum electrolytes between the two groups. In addition, there were no perioperative clinical respiratory and hemodynamic complications in the groups. CONCLUSION: The Hb concentration in the group administered low-dose carperitide at 0.01 µg/kg/min remained higher than that in the control group during surgery. Administration of low-dose carperitide may therefore reduce the risk of blood transfusion during surgery.

Effect of carperitide on in-hospital mortality of patients admitted for heart failure: propensity score analyses.

Although a previous randomized study showed that the use of atrial natriuretic peptide (carperitide) improved the long-term prognosis of patients with heart failure, its effect on short-term prognosis remains unclear. We retrospectively identified patients who were admitted to our tertiary-care center with acute decompensated heart failure (ADHF) between April 2009 and December 2013.We divided the eligible patients into two groups: patients who started receiving carperitide on the day of admission (carperitide group) and those who did not receive carperitide during hospitalization (control group). We compared the in-hospital mortality between the two groups using propensity scores derived from 40 baseline variables. We identified 879 eligible patients (mean age, 75.2 years; male, 56.7%), including 336 (38.2%) in the carperitide group and 543 (61.8%) in the control group. One-to-one propensity score matching created 177 pairs. Although the unmatched analysis found a significantly lower in-hospital mortality in the carperitide group than in the control group (3.3% vs. 7.9%, respectively, p = 0.005), the propensity score-matched analysis found no significant difference in in-hospital mortality between the two groups [4.0% vs. 5.1%, p = 0.609; risk difference, -1.1%, 95% confidence interval (CI), -5.5-3.2%]. Logistic regression analysis with adjustment for propensity scores also found no significant association between carperitide use and in-hospital mortality (adjusted odds ratio, 0.61; 95% CI, 0.29 to 1.28; p = 0.605). The present retrospective study showed that carperitide use as the initial treatment was not significantly associated with lower in-hospital mortality in patients with ADHF.

Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.

Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3 mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48 h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3 g/dl at 7 days after admission. When DAL was defined as ≥0.3 g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.