ABSTRACT
BACKGROUND: Stroke is a common complication of hypertension, but the predictive value of metabolic syndrome parameters' variability on stroke risk in individuals with hypertension remains unclear. Therefore, our objective was to investigate the relationship between metabolic syndrome parameters' variability and the risk of total stroke and its subtypes in hypertensive patients. METHODS: This prospective cohort study included 17,789 individuals with hypertension from the Kailuan study since 2006. Metabolic syndrome parameters, including waist circumference (WC), fasting blood glucose (FBG), systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), were collected at three follow-up visits in the 2006, 2008, and 2010 surveys. We assess the variability utilizing the coefficient of variation (CV), standard deviation (SD), average real variation (ARV), and variability independent of the mean (VIM), with CV initially assessed. Participants were categorized based on the number of high-variability metabolic syndrome parameters (0, 1, 2, ≥ 3). Stroke cases were identified by reviewing medical records. The associations between variability in metabolic syndrome parameters and the risk of total stroke and its subtypes were analyzed using Cox proportional hazard regression models. RESULTS: During a median follow-up of 9.32 years, 1223 cases of stroke were recorded. Participants with ≥ 3 high-variability metabolic syndrome parameters had an increased risk of total stroke (HR: 1.29, 95%CI 1.09-1.52), as well as an increased risk of ischemic stroke (HR: 1.31, 95%CI 1.05-1.63) compared to those without high-variability parameters. The study also examined variability in each metabolic syndrome parameter, and significant associations with an increased risk of total stroke were observed for variability in SBP (HR: 1.24, 95%CI 1.05-1.46) and HDL-C (HR: 1.34, 95%CI 1.09-1.64). CONCLUSIONS: Long-term fluctuations in metabolic syndrome parameters significantly increase the risk of total stroke, especially ischemic stroke. Maintaining low variability in metabolic syndrome parameters could benefit health, and hypertensive individuals must be regularly monitored.
Subject(s)
Biomarkers , Blood Glucose , Blood Pressure , Hypertension , Metabolic Syndrome , Stroke , Humans , Metabolic Syndrome/epidemiology , Metabolic Syndrome/diagnosis , Metabolic Syndrome/blood , Female , Male , Middle Aged , Hypertension/epidemiology , Hypertension/diagnosis , Hypertension/physiopathology , Prospective Studies , Risk Factors , Incidence , Risk Assessment , Aged , Stroke/epidemiology , Stroke/diagnosis , Blood Glucose/metabolism , Time Factors , Biomarkers/blood , China/epidemiology , Prognosis , Triglycerides/blood , Waist Circumference , Cholesterol, HDL/blood , AdultABSTRACT
Metabolic factors are major and controllable risk factors for cardiovascular diseases (CVD), and few studies have described this burden. We aim to assess it from 1990 to 2019 and predict the trends through 2034. Global Burden of Disease (GBD) provides data on sex, age, and socio-demographic index (SDI) levels. Numbers, age-standardized death rates (ASDR) and estimated annual percentage change (EAPC) were used. Future trends were estimated by NORDPRED model. The deaths cases of metabolic-related CVD increased from 8.61 million (95% UI: 7.91-9.29) to 13.71 million (95% UI: 12.24-14.94) globally. The ASDR continued to decline globally (EAPC = -1.36). The burden was heavier in male and middle-aged people and elderly people. CVD-related ASDR caused by high systolic blood pressure (SBP) had a downward trend globally (EAPC = -1.45), while trends of high body mass index (BMI) (EAPC = 1.29, 1.97, 0.92) and fasting plasma glucose (FPG) (EAPC = 0.95, 1.08, 0.46) were increasing in the middle, low-middle, and low SDI regions, respectively. Compared to 2015-2019, cumulative deaths will increase by 27.85% from 2030 to 2034, while ASDR will decrease 10.47%. The metabolic-related CVD burden remained high globally and deaths will continue to rise in the future. Men, middle-aged and elderly people were focus of concern. High SBP was globally well-managed over the past 30 years, but the CVD burden due to high BMI and FPG remained high. Exceptional initiatives are needed to regarding interventions targeting high BMI and FPG in middle and lower SDI regions.
ABSTRACT
Hypertension, diabetes, and hyperlipidemia significantly impact chronic diseases and mortality. Magnesium is an essential nutrient for maintaining critical physiological functions, and magnesium deficiency is often associated with adverse health outcomes. In a cross-sectional study of US adults, we aimed to explore dietary magnesium intake and its association with the prevalence of hypertension, diabetes, and hyperlipidemia in US adults over 20 years of age in NHANES 2007-2018. We obtained data on 24,171 samples of hypertension, 9950 samples of diabetes, and 12,149 samples of hyperlipidemia. We used multivariable logistic regression models adjusted for multiple sociodemographic, anthropometric, and lifestyle factors, with participants subdivided into five groups based on quintiles of daily dietary magnesium. After adjusting for the major lifestyle and dietary variables, an independent and significant inverse relationship between dietary magnesium and hypertension, diabetes, and hyperlipidemia was observed. Compared with the lowest quintile of magnesium intake, the prevalence of hypertension, diabetes, and hyperlipidemia was significantly reduced in the highest magnesium quintile. The OR of hypertension in the highest quintile was 0.66 (95% CI: 0.51-0.87; P trend < 0.001), the OR of diabetes was 0.56 (95% CI: 0.39-0.81; P trend < 0.001), and the OR of hyperlipidemia was 0.68 (95% confidence interval: 0.53-0.86; P trend = 0.007). In the subgroup analysis, most of the inverse relationships persisted. Our findings highlight the potential of magnesium-rich foods to prevent hypertension, diabetes, and hyperlipidemia in US adults. This article summarizes and discuss recent findings on: 1) A high dietary magnesium intake was associated with a lower prevalence of hypertension; 2) An inverse relationship between dietary magnesium with diabetes hyperlipidemia; 3) Monitoring and management of magnesium was important.
Subject(s)
Diabetes Mellitus , Hyperlipidemias , Hypertension , Adult , Humans , Magnesium , Hyperlipidemias/epidemiology , Nutrition Surveys , Cross-Sectional Studies , Diabetes Mellitus/epidemiology , Diet , Hypertension/epidemiology , Risk FactorsABSTRACT
Streptococcus thermophilus FUA329, a urolithin A-producing bacterium, is isolated from human breast milk. The complete genome sequence of FUA329 did not contain any plasmids and at least 20 proteins were related to extreme environment resistance. Phenotypic assay results demonstrated that FUA329 was susceptible to 12 kinds of antibiotics and did not exhibit any hemolytic or nitrate reductase activity. Three free radical scavenging assays revealed that FUA329 have high antioxidant capability. FUA329 exhibited a cell surface hydrophobicity of 52.58 ± 1.17% and an auto-aggregation rate of 18.69 ± 2.48%. Moreover, FUA329 demonstrated a survival rate of over 60% in strong acid and bile salt environments, indicating that FUA329 may be stable colonization in the gastrointestinal tract. Additionally, we firstly found 3 potential proteins and 11 potential genes of transforming ellagic acid to urolithins in FUA329 genome. The above results indicate that FUA329 has credible safety and probiotic properties, as well as the potential to be developed as a new generation of urolithin A-producing probiotics.
Subject(s)
Milk, Human , Probiotics , Female , Humans , Animals , Streptococcus thermophilus/genetics , Streptococcus thermophilus/metabolism , Milk/microbiology , Genomics , Probiotics/metabolismABSTRACT
BACKGROUND: Few studies examined the associations of household fuel combustion with incident diabetes. The current study emphasizes the association of domestic fuel combustion with diabetes among middle- and older- Chinese. METHODS: The data was extracted from a national and prospective cohort, the China Health and Retirement Longitudinal Study (CHARLS), which enrolled adults ≥ 45 years. A total of 4610 and 5570 participants were involved in heating and cooking-related analyses. Multivariable logistic models were conducted to assess the association of domestic fuel combustion for heating and cooking with diabetes. Furthermore, we also examined whether it differed from switching fuel types. Subgroup and interaction analyses were performed based on covariates to examine the robustness and find potential effect modifiers. RESULTS: After about 5-year follow-up, 592 and 716 diabetes were diagnosed in heating and cooking-related analyses. Compared to cleaner fuel users, those who used solid fuel for heating [OR (95 % CI):1.32 (1.05-1.66)] maintained higher risks of incident diabetes. In addition, participants who were exposed to solid fuel for both heating and cooking [OR (95 % CI):1.55 (1.17-2.06)] might have further elevated diabetic risk. Those risks are likely to be attenuated if people switched cooking fuel from solid to cleaner [OR (95 % CI): 0.68 (0.53-0.89)]. CONCLUSIONS: Home solid fuel use for heating is associated with an increased risk of incident diabetes. If solid fuel was concurrently used for both cooking and heating, those risks might be further elevated. Interestingly, as compared to solid fuel users, the participants switching cooking fuel types from solid to cleaner presented reduced diabetic risk.
Subject(s)
Air Pollution, Indoor , Diabetes Mellitus , Middle Aged , Humans , Aged , Cohort Studies , Prospective Studies , Longitudinal Studies , Air Pollution, Indoor/adverse effects , Coal/adverse effects , China/epidemiology , Cooking , Diabetes Mellitus/etiology , Diabetes Mellitus/chemically inducedABSTRACT
Myrosinase can hydrolyze glucosinolates to generate isothiocyanates, which have cancer prevention and anti-cancer properties. The main sources of myrosinase are cruciferous plants. To further improve the efficiency of isothiocyanates preparation, it is necessary to explore novel sources of myrosinases. In this study, we described a bacterium, Shewanella baltica Myr-37, isolated from marine mud, capable of producing a novel myrosinase (Smyr37) with a molecular weight of 100 kDa. The crude enzyme of Smyr37 showed the highest activity at 50 °C and pH 8.0. The sinigrin- and glucoraphanin-hydrolyzing activities of Smyr37 were 6.95 and 5.87 U/mg, respectively. Moreover, when the reaction temperature was 40 °C and pH was 7.0, the crude enzyme of Smyr37 could efficiently degrade glucoraphanin into sulforaphane within 25 min with a yield of 0.57 mg/mL. The corresponding conversion efficiency of sulforaphane from glucoraphanin was 89%. In summary, S. baltica Myr-37 myrosinase Smyr37, a novel myrosinase, can be used in the preparation of isothiocyanates.
Subject(s)
Brassica , Shewanella , Brassica/metabolism , Glucosinolates/metabolism , Glycoside Hydrolases/metabolism , Isothiocyanates/metabolism , Oximes , Shewanella/metabolism , SulfoxidesABSTRACT
The molecules at the surface of a liquid have different organization and dynamics from those in the bulk, potentially altering the rate of crystal nucleation and polymorphic selection, but this effect remains poorly understood. Here we demonstrate that nucleation at the surface of a pure liquid, d-arabitol, is vastly enhanced, by 12 orders of magnitude, and selects a different polymorph. The surface effect intensifies with cooling and can be inhibited by a dilute, surface-active second component. This phenomenon arises from the anisotropic molecular packing at the interface and its similarity to the surface-nucleating polymorph. Our finding is relevant for controlling the crystallization and polymorphism in any system with a significant interface such as nanodroplets and atmospheric water.
Subject(s)
Crystallization , Anisotropy , Phase TransitionABSTRACT
Chitin deacetylase (CDA) inhibitors were developed as novel antifungal agents because CDA participates in critical fungal physiological and metabolic processes and increases virulence in soilborne fungal pathogens. However, few CDA inhibitors have been reported. In this study, 150 candidate CDA inhibitors were selected from the commercial Chemdiv compound library through structure-based virtual screening. The top-ranked 25 compounds were further evaluated for biological activity. The compound J075-4187 had an IC50 of 4.24 ± 0.16 µM for AnCDA. Molecular docking calculations predicted that compound J075-4187 binds to the amino acid residues, including active sites (H101, D48). Furthermore, compound J075-4187 inhibited food spoilage fungi and plant pathogenic fungi, with minimum inhibitory concentration (MIC) at 260 µg/ml and minimum fungicidal concentration (MFC) at 520 µg/ml. Therefore, compound J075-4187 is a good candidate for use in developing antifungal agents for fungi control.
Subject(s)
Amidohydrolases , Antifungal Agents , Amidohydrolases/metabolism , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Biological Assay , Chitin/metabolism , Microbial Sensitivity Tests , Molecular Docking SimulationABSTRACT
In this study, chitin deacetylase from Microbacterium esteraromaticum MCDA02 (MeCDA) was purified by ammonium sulfate precipitation, anion exchange chromatography, and superdex column chromatography. The molecular weight of purified MeCDA was approximately 26 kDa. The optimum pH and temperature of purified MeCDA were 8.0 and 30 °C, respectively. The enzyme activity is enhanced by metal ions K+ and Sr+ and inhibited by Co2+, Cd2+, and EDTA. The degree of deacetylation through enzymatic modification of MeCDA was removed an average of 32.75% of the acetyl groups for É-chitin by acid-base titration. Meanwhile, MeCDA can catalyze the hydrolytic cleavage of the acetamido bond in GlcNAc units within chitin oligomers and polymers. Hence, the MeCDA is a potent chitin decomposer to catalyze chitin and chitin oligosaccharides deacetylation to prepare chitosan and chitosan oligosaccharide. This is a value-added utilization of chitin based biological resources.
Subject(s)
Chitin , Chitosan , Amidohydrolases/chemistry , Chitin/chemistry , Chitosan/chemistry , Microbacterium , Oligosaccharides/chemistryABSTRACT
Urolithin A, a metabolite of ellagic acid, has many beneficial biological activities for people. Strains capable of producing urolithin A from ellagic acid have the hope of becoming the next-generation probiotics. However, only a few species of these strains have been reported. In this study, FUA329, a strain capable of converting ellagic acid to urolithin A in vitro, was isolated from the breast milk of healthy Chinese women. The results of morphological observation, physiological and biochemical tests, and 16S rRNA gene sequence analysis confirmed that the strain FUA329 was Streptococcus thermophilus. In addition, the S. thermophilus FUA329 growth phase is consistent with the degradation of ellagic acid, and urolithin A was produced in the stationary phase, with a maximum concentration of 7.38 µM at 50 h. The corresponding conversion efficiency of urolithin A from ellagic acid was 82%. In summary, S. thermophilus FUA329, a novel urolithin A-producing bacterium, would be useful for the industrial production of urolithin A and may be developed as a next-generation probiotic.
ABSTRACT
As a symptomatic predementia stage with progressive cognitive decline, mild cognitive impairment (MCI) is common with aging. How changes in self-reported sleep duration affect MCI risk in the older adults remains unclear. Participants aged ≥ 65 years and enrolled at least two waves in the Chinese Longitudinal Healthy Longevity Survey were included in present longitudinal study. Changes in sleep duration were calculated as the difference between two waves and categorized into five groups: decreased >2 h, decreased 0-2h, stable, increased 0-2 h, and increased >2 h. MCI was measured by the Chinese version of the Mini-Mental State Examination. Generalized estimating equation model and restricted cubic spline function was applied to investigate the association. Among 9,005 participants (mean age, 81.19 years; 4,391 male), 2,877 developed MCI. Comparing with individuals with stable sleep duration, MCI risk [odds ratio (95% confidence intervals)] was: 1.15 (0.99-1.34) for decreased >2 h, 0.99 (0.87-1.13) for decreased 0-2h, 1.09 (0.95-1.24) for increased 0-2 h, and 1.57 (1.36-1.81) for increased >2 h, respectively. Similar patterns were observed among subgroup analyses by sex, age, and sleep quality at baseline. For participants with long sleep duration at baseline (>8h), further increased >2 h was associated with higher MCI risk [2.23 (1.55-3.21)]. Either in the whole or subgroup population, a U-shaped association was observed (Pnon-linearity<0.05). In conclusion, changes in self-reported sleep duration were associated with MCI risk in a U-shaped pattern. Strategies that shifting sleep duration into normal range and keeping it stable are essential to prevent MCI in clinical practice.
Subject(s)
Cognitive Dysfunction/physiopathology , Self Report , Sleep/physiology , Aged , Aged, 80 and over , China , Female , Humans , Longitudinal Studies , Male , Risk FactorsABSTRACT
Objective To investigate the effects of inorganic arsenic exposure on the differentiation of renal CD4+T lymphocytes and the possible mechanism. Methods Female C57BL/6 mice were randomly divided into control group, (2.5, 5, 10) mg/kg NaAsO2 exposure groups, 10 mice in each group. As was administered once intragastrically for 24 hours, and control mice were treated with normal saline. Real-time fluorescence quantitative PCR was used to detect T helper type 1 (Th1) cell-specific transcription factor T-box expressed in T cells (T-bet) and IFN-γ, Th2 cell-specific transcription factor GATA-binding protein 3 (GATA3) and interleukin 4 (IL-4), Th17 cell-specific transcription factor retinoic acid related orphan nuclear receptor γt (ROR-γt) and cytokine IL-22, regulatory T cells (Tregs)-specific transcription factor forkhead box P3 (FOXP3) and cytokine transforming growth factor-ß (TGF-ß) mRNA levels. We used commercial kits to detect catalase (CAT) activity and total antioxidant capacity (T-AOC) in serum as well as renal malondialdehyde (MDA) and superoxide dismutase (SOD). Results Compared with the control group, the body mass, renal mass and kidney index of the mice in all arsenic-treated groups have no significant changes. The levels of the master transcription factors T-bet, GATA3, ROR-γt and FOXP3 as well as related cytokines IFN-γ, IL-4, IL-22 and TGF-ß of Th1, Th2, Th17 cells and Tregs decreased in the arsenic-treated groups. Serum CAT activity and T-AOC level in the arsenic-treated mice dropped greatly. In addition, arsenic markedly increased renal MDA level while decreased SOD activity. Conclusion Inorganic arsenic exposure can suppress renal T cell subpopulation function and induce renal oxidative injure.
Subject(s)
Arsenic/toxicity , Kidney/drug effects , Oxidative Stress , T-Lymphocytes, Regulatory/drug effects , Th1 Cells/drug effects , Th2 Cells/drug effects , Animals , Cytokines/metabolism , Female , Forkhead Transcription Factors/metabolism , GATA3 Transcription Factor/metabolism , Kidney/immunology , Mice , Mice, Inbred C57BLABSTRACT
As the industries advances at a fast pace, efficient and simultaneous removal of both heavy metals and organics from aqueous is essential to protecting public human health and environment. In this work, we used pyrite as reductant and catalyst for simultaneously reducing Cr(VI) and activating persulfate (PS) to degrade acid orange 7 (AO7). The results indicated that the simultaneous removal rate of AO7 and Cr(VI) by pyrite-PS was up to 100% within 60 min under acidic conditions. However, There was a competitive relationship between PS activation and Cr(VI) reduction for robbing Fe2+. At beginning of the reaction, the limited Fe2+ firstly activated persulfate rather than reduce Cr(VI). The effect of dosage of pyrite and PS on Cr(VI) reduction was more significant than that on AO7 degradation. Increased pyrite dosages from 1g·L-1 to 6 g L-1 resulted in enhanced Cr(VI) removal, and excessive PS (more than 0.4 g L-1) was not beneficial to Cr(VI) removal. Electron paramagnetic resonance (EPR) spectroscopy and radical scavenger studies demonstrated that sulfate (SO4-·), singlet oxygen (1O2) and superoxide radical (·O2-) were the crucial reactive oxygen species (ROS) in the pyrite-PS system rather than hydroxyl radical (·OH). This study showed that the pyrite-PS system could simultaneously remove AO7 and Cr(VI), which provided a new idea for the actual wastewater treatment.
Subject(s)
Water Pollutants, Chemical , Water , Azo Compounds , Benzenesulfonates , Chromium , Iron , Oxidation-Reduction , Sulfides , Wastewater , Water Pollutants, Chemical/analysisABSTRACT
OBJECTIVE: The aim of this study was to investigate the anatomical imaging characteristics of posterior ethmoid cells (PEs) expanding towards the inferolateral region of the sphenoid sinus (SS). METHODS: This study included a total of 278 inpatients (556 sides) whose paranasal sinus computed tomography (CT) scans were reviewed and collected from May 2018 to February 2019. The anatomical imaging characteristics of PEs expanding towards the inferolateral region of the SS were observed. RESULTS: PEs expanding towards the inferolateral region of the SS formed an inferolateral spheno-ethmoid cell (ISEC). ISECs were observed on three sides (0.54%; 3/556) in three cases (1.08%; 3/278). All of the ISECs were present unilaterally on the right side of the SS. The ISECs originated from the most posterior ethmoid cell; they were first located at the medial aspect of the orbital apex, pneumatized continually backward to the inferomedial wall of the orbital apex, and then extended into the lateral region of the SS. The ISECs further extended laterally, inferiorly and posteriorly beyond the sphenoid body into the greater wing and/or pterygoid process. CONCLUSION: An ISEC is a rare variation of ethmoid air cells. Preoperative recognition of ISECs is essential to achieve safe and effective endoscopic sinus surgery because of the important anatomical location.
Subject(s)
Anatomic Variation , Ethmoid Sinus/anatomy & histology , Sphenoid Sinus/anatomy & histology , Adolescent , Adult , Aged , Ethmoid Sinus/diagnostic imaging , Female , Humans , Male , Middle Aged , Retrospective Studies , Sphenoid Sinus/diagnostic imaging , Tomography, X-Ray Computed , Young AdultABSTRACT
Acute pulmonary embolism (APE) with cardiac arrest (CA) is associated with a high mortality rate. Even upon return of the spontaneous circulation (ROSC), APECA survivors are prone to myocardial cell apoptosis, a key cellular mechanism that induces heart failure. A recent study by our group discovered a postresuscitation imbalance in the serum angiotensinconverting enzyme (ACE)2/ACE axis of the reninangiotensin system (RAS), as well as regressive cardiac function in a porcine model of APECA. However, it has remained elusive how this imbalance in the ACE2/ACE axis affects myocardial cell apoptosis. In the present study, western blot and immunohistochemical analyses demonstrated that the RAS was only activated in the left myocardium, as evidenced by a decreased ACE2/ACE ratio following APECA and ROSC, but not the right myocardium. Ultrastructural analysis confirmed myocardial apoptosis in the left and right myocardium. Furthermore, Bcell lymphoma 2 (Bcl2)associated X protein (Bax) and caspase3 levels were elevated and Bcl2 levels were decreased in the left myocardium following APECA and ROSC. Treatment with the ACE inhibitor captopril for 30 min after initiation of ROSC prevented the increase in Bax and the decrease in Bcl2 in the left myocardium compared with that in salinetreated pigs. Captopril also inhibited the activation of extracellular signalregulated kinase (ERK)1/2 in the left myocardium. The results of the present study suggest that an imbalance in the ACE2/ACE axis has an important role in myocardial apoptosis following APECA, which may be attributed to decreased ERK1/2 activation. In addition, it was indicated that captopril prevents apoptosis in the left myocardium after ROSC.
Subject(s)
Apoptosis , Heart Arrest/enzymology , Heart Arrest/etiology , Myocardium/enzymology , Myocardium/pathology , Peptidyl-Dipeptidase A/metabolism , Pulmonary Embolism/complications , Acute Disease , Angiotensin-Converting Enzyme 2 , Animals , Apoptosis/drug effects , Captopril/pharmacology , Disease Models, Animal , Enzyme Activation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Myocardium/ultrastructure , Renin-Angiotensin System/drug effects , Signal Transduction/drug effects , SwineABSTRACT
Acute pulmonary embolism (APE) is frequently reported in patients with cardiac arrest (CA) in emergency care. Pneumocyte apoptosis is commonly observed in the lungs following an APE. An important pathological mechanism evoking apoptosis during a lipopolysaccharideinduced acute lung injury is the angiotensinconverting enzyme 2 (ACE2)/ACE imbalance. The present study uses a porcine model to examine the antiapoptotic effects of captopril on APECA and the return of spontaneous circulation (ROSC). Pigs were randomly assigned into four groups: Control, APECA, ROSCsaline, and ROSCcaptopril. Surviving pigs were euthanized at 6 h and lungs were isolated for analysis using several biochemical assays. Compared with the control group, the ACE2/ACE ratio was lower in the APECA and ROSC pigs. In addition, APECA pigs had higher Bcl2associated X protein (Bax) and cleaved caspase3 levels, and lower Bcell lymphoma2 (Bcl2) level compared to control pigs. Captopril treatment reduced lung apoptosis, as demonstrated by lower TUNELpositive cells, higher Bcl2, and lower cleaved caspase3 protein levels in the lung. Notably, the ACE2/ACE ratio was positively correlated with Bcl2 protein levels and Bcl2/Bax ratio. In conclusion, captopril has a protective effect against lung apoptosis following ROSC and that maintaining the balance of the ACE2/ACE axis is important for inhibiting pulmonary apoptosis during APE.
Subject(s)
Acute Lung Injury/drug therapy , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Captopril/pharmacology , Heart Arrest/drug therapy , Peptidyl-Dipeptidase A/genetics , Pulmonary Embolism/drug therapy , Acute Lung Injury/chemically induced , Acute Lung Injury/genetics , Acute Lung Injury/pathology , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Angiotensin-Converting Enzyme 2 , Animals , Apoptosis/drug effects , Caspase 3/genetics , Caspase 3/metabolism , Disease Models, Animal , Female , Gene Expression Regulation , Heart Arrest/chemically induced , Heart Arrest/genetics , Heart Arrest/pathology , Lipopolysaccharides , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Peptidyl-Dipeptidase A/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Pulmonary Embolism/chemically induced , Pulmonary Embolism/genetics , Pulmonary Embolism/pathology , Signal Transduction , SwineABSTRACT
Acute pulmonary embolism (APE) has a very high mortality rate, especially at cardiac arrest and even after the return of spontaneous circulation (ROSC). This study investigated the protective effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on postresuscitation hemodynamics, in a porcine model of cardiac arrest established by APE. Twenty-nine Beijing Landrace pigs were infused with an autologous thrombus leading to cardiac arrest and subjected to standard cardiopulmonary resuscitation and thrombolysis. Ten resuscitated pigs were randomly and equally apportioned to receive either captopril (22.22 mg/kg) infusion or the same volume saline, 30 min after ROSC. Hemodynamic changes and ACE-Ang II-angiotensin II type 1 receptor (AT1R) and ACE2/Ang-(1-7)/Mas receptor axis levels were determined. APE was associated with a decline in mean arterial pressure and a dramatic increase in pulmonary artery pressure and mean right ventricular pressure. After ROSC, captopril infusion was associated with significantly lower mean right ventricular pressure and systemic and pulmonary vascular resistance, faster heart rate, and higher Ang-(1-7) levels, ACE2/ACE, and Ang-(1-7)/Ang II, compared with the saline infusion. The ACE2/Ang-(1-7)/Mas pathway correlated negatively with external vascular lung water and pulmonary vascular permeability and positively with the right cardiac index. In conclusion, in a pig model of APE leading to cardiac arrest, captopril infusion was associated with less mean right ventricular pressure overload after resuscitation, compared with saline infusion. The reduction in systemic and pulmonary vascular resistance associated with captopril may be by inhibiting the ACE-Ang II-AT1R axis and activating the ACE2/Ang-(1-7)/Mas axis.