Atrial natriuretic peptide (ANP) modulates stress-induced autophagy in endothelial cells.

Atrial natriuretic peptide (ANP), a cardiac hormone involved in the regulation of water/sodium balance and blood pressure, is also secreted by endothelial cells, where it exerts protective effects in response to stress. Autophagy is an intracellular self-renewal process involved in the degradation of dysfunctional cytoplasmic elements. ANP was recently reported to act as an extracellular regulator of cardiac autophagy. However, its role in the regulation of endothelial autophagy has never been investigated. Here, we tested the effects of ANP in the regulation of autophagy in human umbilical vein endothelial cells (HUVECs). We found that ANP rapidly increases autophagy and autophagic flux at physiological concentrations through its predominant pathway, mediated by natriuretic peptide receptor type A (NPR-A) and protein kinase G (PKG). We further observed that ANP is rapidly secreted by HUVEC under stress conditions, where it mediates stress-induced autophagy through autocrine and paracrine mechanisms. Finally, we found that the protective effects of ANP in response to high-salt loading or tumor necrosis factor (TNF)-α are blunted by concomitant inhibition of autophagy. Overall, our results suggest that ANP acts as an endogenous autophagy activator in endothelial cells. The autophagy mechanism mediates the protective endothelial effects exerted by ANP.

Deletion of AT1a receptors selectively in the proximal tubules alters the hypotensive and natriuretic response to ANP via NPRA/cGMP/NO Signaling.

In the kidney, vasoactive peptide hormones angiotensin II (Ang II), via AT1a receptors, and atrial natriuretic peptide (ANP), via NPRA receptors, reportedly play counteracting roles to regulate proximal tubule Na+ reabsorption and maintain blood pressure homeostasis. However, how AT1a and NPRA receptors interact in the proximal tubules and whether deletion of AT1 (AT1a) receptors selectively in the proximal tubules alters the hypotensive and natriuretic effects of ANP) have not been studied previously. The present study used a novel mouse model with proximal tubule-specific knockout of AT1a receptors to test the hypothesis that deletion of AT1a receptors selectively in the proximal tubules augments the hypotensive and natriuretic responses to ANP. Basal blood pressure was about 16 ± 3 mmHg lower, fractional proximal tubule Na+ reabsorption was significantly lower, whereas 24 h urinary Na+ excretion was significantly higher in PT-Agtr1a-/- than in wild-type mice (P<0.01). Infusion of ANP for 2 weeks (0.5 mg/kg/day, i.p.) further significantly decreased blood pressure and increased the natriuretic response in PT-Agtr1a-/- mice by inhibiting proximal tubule Na+ reabsorption (P<0.01). These augmented hypotensive and natriuretic responses to ANP in PT-Agtr1a-/- mice were associated with increased plasma and kidney cGMP levels (P<0.01), kidney cortical NPRA and NPRC mRNA expression (P<0.01), total and phosphorylated endothelial nitric oxide synthase (eNOS) (P<0.01), and urinary nitric oxide (NO) excretion (P<0.01). Taken together, the results of the present study support important physiological roles of Ang II/AT1a and ANP/NPRA signaling pathways in the proximal tubules to regulate proximal tubule reabsorption and maintain blood pressure homeostasis.

Natriuretic peptides and soluble ST2 improves echocardiographic diagnosis of elevated left ventricular filling pressures.

Elevated filling pressure of the left ventricle (LV) defines diastolic dysfunction. The gold standard for diagnosis is represented by the measurement of LV end-diastolic pressure (LVEDP) during cardiac catheterization, but it has the disadvantage of being an invasive procedure. This study aimed to investigate the correlation between LVEDP and cardiac serum biomarkers such as natriuretic peptides (mid-regional pro-atrial natriuretic peptide [MR-proANP], B-type natriuretic peptide [BNP], and N-terminal prohormone BNP [NT-proBNP]), soluble ST2 (sST2), galectin-3 and mid-regional pro-adrenomedullin (MR-proAMD). Consecutive patients hospitalized in a tertiary center and undergoing left cardiac catheterization were included in the study. Diastolic dysfunction was considered present if the end-expiratory LVEDP was ≥ 15 mmHg. Cardiac biomarkers were determined from pre-procedural peripheral venous blood samples. A total of 110 patients were included, of whom 76 (69.0%) were males, with a median age of 65 (55-71) years. Median LVEDP was 13.5 (8-19) mmHg and diastolic dysfunction was present in 50 (45.4%) of the patients. LVEDP correlated with BNP (p < 0.0001, r = 0.39 [0.20-0.53]), NT-proBNP (p < 0.0001, r = 0.40 [0.22-0.55]), MR-proANP (p = 0.001, r = 0.30 [0.11-0.46]), sST2 (p < 0.0001, r = 0.47 [0.30-0.60]), but not with MR-proAMD (p = 0.77) or galectin-3 (p = 0.76). In the final stepwise multivariable binary logistic regression model, diastolic dysfunction was predicted by NT-proBNP, mitral average E/e', sST2, atrial fibrillation, and left atrium reservoir strain. BNP, NT-proBNP, MR-proANP, and sST2 had predictive value for diastolic dysfunction. In contrast, galectin-3 and MR-proAMD were not associated with increased filling pressures. Furthermore, NT-proBNP and sST2 significantly improved diastolic dysfunction prediction in the final multivariable model.

Endothelial glycocalyx degradation in critically ill foals.

BACKGROUND: Endothelial glycocalyx (EG) degradation occurs in septic humans and EG products can be used as biomarkers of endothelial injury. Information about EG biomarkers and their association with disease severity is lacking in hospitalized foals. OBJECTIVES: Measure serum syndecan-1 (SDC-1), heparan sulfate (HS), angiopoietin-2 (ANG-2), aldosterone (ALD), and plasma atrial natriuretic peptide (ANP) concentrations and to determine their association with disease severity and death in hospitalized foals. ANIMALS: Ninety foals ≤3 days old. METHODS: Prospective, multicenter, longitudinal study. Foals were categorized into hospitalized (n = 74; 55 septic; 19 sick nonseptic) and 16 healthy foals. Serum ([SDC-1], [HS], [ANG-2], [ALD]) and plasma (ANP) were measured over 72 hours using immunoassays. RESULTS: Serum ([SDC-1], [HS], [ANG-2], [ALD]) and plasma (ANP) were significantly higher in hospitalized and septic than healthy foals (P < .05). Serum (ANG-2) and plasma (ANP) were significantly higher in hospitalized nonsurvivors than in survivors (P < .05). On admission, hospitalized foals with serum (HS) > 58.7 ng/mL had higher odds of nonsurvival (odds ratio [OR] = 6.1; 95% confidence interval [CI] = 1.02-36.7). Plasma (ANP) >11.5 pg/mL was associated with the likelihood of nonsurvival in hospitalized foals (OR = 7.2; 95% CI = 1.4-37.4; P < .05). Septic foals with serum (ANG-2) >1018 pg/mL on admission had higher odds of nonsurvival (OR = 6.5; 95% CI =1.2-36.6; P < .05). CONCLUSION AND CLINICAL IMPORTANCE: Critical illness in newborn foals is associated with EG degradation and injury, and these biomarkers are related to the severity of disease on admission and the outcome of sick foals.

Cholecystokinin regulates atrial natriuretic peptide secretion through activation of NOX4-Sirt1-LEF1 signaling in beating rat hypoxic atria.

The mammalian cardiac myocytes not only synthesize and secrete atrial natriuretic peptide (ANP), but also express cholecystokinin (CCK) and its receptors (CCK1R and CCK2R). However, atrial CCK expression patterns and its effects on ANP secretion during hypoxia are unclear. Therefore, this study is aimed to investigate the effect of hypoxia on the expression levels of CCK and its receptors, as well as the underlying mechanisms involved in regulating hypoxia-induced ANP secretion in isolated beating atria. The results of this study showed that acute hypoxia significantly upregulated expression of CCK and CCK1R as well as CCK2R through activation of hypoxia-inducible factor 1α-apelin signaling. Endogenous CCK induced by hypoxia markedly upregulated the expression of silent information regulator factor 2-related enzyme 1 (Sirt1) and its downstream nuclear factor erythroid­2­related factor 2 (Nrf2) via the activation of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), leading to increase of activating T cell factor (TCF) 3 and TCF4/ lymphoid enhancer factor (LEF) 1, ultimately promoting hypoxia-induced ANP secretion. In addition, siRNA-mediated knockdown of LEF1 dramatically attenuated hypoxia-induced increase of ANP expression in HL-1 atrial myocytes. These results indicated endogenous CCK induced by hypoxia promoted hypoxia-induced ANP secretion by activation of NOX4-Sirt1-TCF3/4-LEF1 signaling pathway.

Matairesinol blunts adverse cardiac remodeling and heart failure induced by pressure overload by regulating Prdx1 and PI3K/AKT/FOXO1 signaling.

BACKGROUND: Pathological cardiac remodeling is a critical process leading to heart failure, characterized primarily by inflammation and apoptosis. Matairesinol (Mat), a key chemical component of Podocarpus macrophyllus resin, exhibits a wide range of pharmacological activities, including anti-hydatid, antioxidant, antitumor, and anti-inflammatory effects. PURPOSE: This study aims to investigate whether Matairesinol alleviate cardiac hypertrophy and remodeling caused by pressure overload and to elucidate its mechanism of action. METHODS: An in vitro pressure loading model was established using neonatal rat cardiomyocytes treated with angiotensin Ⅱ, while an in vivo model was created using C57 mice subjected to transverse aortic constriction (TAC). To activate the PI3K/Akt/FoxO1 pathway, Ys-49 was employed. Moreover, small interfering RNA (siRNA) and short hairpin RNA (shRNA) were utilized to silence Prdx1 expression both in vitro and in vivo. Various techniques, including echocardiography, wheat germ agglutinin (WGA) staining, HE staining, PSR staining, and Masson trichrome staining, were used to assess cardiac function, cardiomyocyte cross-sectional area, and fibrosis levels in rats. Apoptosis in myocardial tissue and in vitro was detected by TUNEL assay, while reactive oxygen species (ROS) content in tissues and cells was measured using DHE staining. Furthermore, the affinity of Prdx1 with Mat and PI3K was analyzed using computer-simulated molecular docking. Western blotting and RT-PCR were utilized to evaluate Prdx1 levels and proteins related to apoptosis and oxidative stress, as well as the mRNA levels of cardiac hypertrophy and fibrosis-related indicators. RESULTS: Mat significantly alleviated cardiac hypertrophy and fibrosis induced by TAC, preserved cardiac function, and markedly reduced cardiomyocyte apoptosis and oxidative damage. In vitro, mat attenuated ang Ⅱ - induced hypertrophy of nrvms and activation of neonatal rat fibroblasts. Notably, activation of the PI3K/Akt/FoxO1 pathway and downregulation of Prdx1 expression were observed in TAC mice; however, these effects were reversed by Mat treatment. Furthermore, Prdx1 knockdown activated the PI3K/Akt/FoxO1 pathway, leading to exacerbation of the disease. Molecular docking indicated that Molecular docking indicated that Mat upregulated Prdx1 expression by binding to it, thereby inhibiting the PI3K/Akt/FoxO1 pathway and protecting the heart by restoring Prdx1 expression levels. CONCLUSION: Matairesinol alleviates pressure overload-induced cardiac remodeling both in vivo and in vitro by upregulating Prdx1 expression and inhibiting the PI3K/Akt/FoxO1 pathway. This study highlights the therapeutic potential of Matairesinol in the treatment of cardiac hypertrophy and remodeling, providing a promising avenue for future research and clinical application.

Evaluation of plasma atrial natriuretic peptide concentration in healthy bottlenose dolphins (Tursiops truncates).

There are currently no standard methods for diagnosing cardiac diseases in dolphins. These diseases may consequently be overlooked and go undiagnosed. The presence and severity of cardiac diseases in humans can be determined using blood tests. Atrial natriuretic peptide (ANP) used in human cardiac examinations has low species specificity. There have already been reports of homology between dolphin and human ANP; however, its potential for clinical application in dolphins has not been tested. This study was conducted to establish a reference for ANP levels in healthy bottlenose dolphins. Healthy bottlenose dolphins (seven females; estimated to be 7-30 years of age) at an aquarium in Japan were sampled. Each animal was tested for ANP at least three times, and the mean value and standard deviation were calculated to be 43.4 ± 19.2 pg/mL. In humans, patients with high plasma ANP levels have a poor prognosis. In veterinary medicine, cutoff values for the diagnosis of mitral regurgitation and heart failure in dogs have been established and used to predict prognosis. The results of the present study may contribute to the health management of bottlenose dolphins, particularly in the early detection and treatment of cardiac diseases.

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.

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.

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.