ABSTRACT
Obesity-related hypertension (OH) is accompanied by obvious endothelial dysfunction, which contributes to increased peripheral vascular resistance and hypertension. Adrenomedullin (ADM), a multifunctional active peptide, is elevated in obese humans. The OH rats induced by high fat diet (HFD) for 28 weeks and the human umbilical vein endothelial cells (HUVECs)-treated by palmitic acid (PA) were used to investigate the effects of ADM on endothelial dysfunction and the underlying mechanisms. Vascular reactivity was assessed using mesenteric arteriole rings, and the protein expression levels were examined by Western blot analysis. Compared with the control rats, OH rats exhibited hypertension and endothelial dysfunction, along with reduced eNOS protein expression and Akt activation, and increased protein expression of proinflammatory cytokines and ROS levels. Four-week ADM administration improved hypertension and endothelial function, increased eNOS protein expression and Akt activation, and attenuated endothelial inflammation and oxidative stress in OH rats. In vitro experiment, the antagonism of ADM receptors with ADM22-52 and the suppression of Akt signaling with A6730 significantly blocked ADM-caused increase of NO content and activation of eNOS and Akt, and inhibited the anti-inflammatory and anti-oxidant effect of ADM in PA-stimulated HUVECs. These data indicate that endothelial dysfunction in OH rats is partially attributable to the decreased NO level, and the increased inflammation and oxidative stress. ADM improves endothelial function and exerts hypotensive effect depending on the increase of NO, and its anti-inflammatory and anti-oxidant effect via receptor-Akt pathway.
Subject(s)
Adrenomedullin , Endothelium, Vascular , Human Umbilical Vein Endothelial Cells , Hypertension , Nitric Oxide Synthase Type III , Obesity , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Signal Transduction , Animals , Adrenomedullin/pharmacology , Adrenomedullin/metabolism , Male , Obesity/complications , Obesity/metabolism , Hypertension/metabolism , Hypertension/physiopathology , Rats , Proto-Oncogene Proteins c-akt/metabolism , Humans , Human Umbilical Vein Endothelial Cells/drug effects , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Endothelium, Vascular/metabolism , Signal Transduction/drug effects , Nitric Oxide Synthase Type III/metabolism , Diet, High-Fat/adverse effects , Oxidative Stress/drug effects , Receptors, Adrenomedullin/metabolism , Peptide FragmentsABSTRACT
Adrenomedullin (ADM) is a novel cardiovascular peptide with anti-inflammatory and antioxidant properties. Chronic inflammation, oxidative stress and calcification play pivotal roles in the pathogenesis of vascular dysfunction in obesity-related hypertension (OH). Our study aimed to explore the effects of ADM on the vascular inflammation, oxidative stress and calcification in rats with OH. Eight-week-old Sprague Dawley male rats were fed with either a Control diet or a high fat diet (HFD) for 28 weeks. Next, the OH rats were randomly subdivided into two groups as follows: (1) HFD control group, and (2) HFD with ADM. A 4-week treatment with ADM (7.2 µg/kg/day, ip) not only improved hypertension and vascular remodeling, but also inhibited vascular inflammation, oxidative stress and calcification in aorta of rats with OH. In vitro experiments, ADM (10 nM) in A7r5 cells (rat thoracic aorta smooth muscle cells) attenuated palmitic acid (PA, 200 µM) or angiotensin II (Ang II, 10 nM) alone or their combination treatment-induced inflammation, oxidative stress and calcification, which were effectively inhibited by the ADM receptor antagonist ADM22-52 and AMP-activated protein kinase (AMPK) inhibitor Compound C, respectively. Moreover, ADM treatment significantly inhibited Ang II type 1 receptor (AT1R) protein expression in aorta of rats with OH or in PA-treated A7r5 cells. ADM improved hypertension, vascular remodeling and arterial stiffness, and attenuated inflammation, oxidative stress and calcification in OH state partially via receptor-mediated AMPK pathway. The results also raise the possibility that ADM will be considered for improving hypertension and vascular damage in patients with OH.
Subject(s)
Adrenomedullin , Anti-Inflammatory Agents , Antioxidants , Hypertension , Obesity , Animals , Male , Rats , Adrenomedullin/pharmacology , Adrenomedullin/therapeutic use , AMP-Activated Protein Kinases , Calcinosis/complications , Hypertension/drug therapy , Hypertension/etiology , Hypertension/metabolism , Inflammation/complications , Obesity/complications , Rats, Sprague-Dawley , Vascular Remodeling , Antioxidants/pharmacology , Antioxidants/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic useABSTRACT
BACKGROUND: Hypothalamic paraventricular nucleus (PVN) is an important central site for the control of the adipose afferent reflex (AAR) that increases sympathetic outflow and blood pressure in obesity-related hypertension (OH). METHOD: In this study, we investigated the effects of nitric oxide (NO) and cardiovascular bioactive polypeptide adrenomedullin (ADM) in the PVN on AAR and sympathetic nerve activity (SNA) in OH rats induced by a high-fat diet. RESULTS: The results showed that ADM, total neuronal NO synthase (nNOS) and phosphorylated-nNOS protein expression levels in the PVN of the OH rats were down-regulated compared to the control rats. The enhanced AAR in OH rats was attenuated by PVN acute application of NO donor sodium nitroprusside (SNP), but was strengthened by the nNOS inhibitor nNOS-I, guanylyl cyclase inhibitor (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) and gamma-aminobutyric acid A type receptor (GABAA) antagonist Bicuculline. Moreover, PVN ADM microinjection not only decreased basal SNA but also attenuated the enhanced AAR in OH rats, which were effectively inhibited by ADM receptor antagonist ADM22-52, nNOS-I, ODQ or Bicuculline pretreatment. Bilateral PVN acute microinjection of ADM also caused greater increases in NO and cyclic guanosine monophosphate (cGMP) levels, and nNOS phosphorylation. Adeno-associated virus vectors encoding ADM (AAV-ADM) transfection in the PVN of OH rats not only decreased the elevated AAR, basal SNA and blood pressure (BP), but also increased the expression and activation of nNOS. Furthermore, AAV-ADM transfection improved vascular remodeling in OH rats. CONCLUSION: Taken together, our data highlight the roles of ADM in improving sympathetic overactivation, enhanced AAR and hypertension, and its related mechanisms associated with receptors mediated NO-cGMP-GABAA pathway in OH condition.
Subject(s)
Hypertension , Paraventricular Hypothalamic Nucleus , Rats , Animals , Paraventricular Hypothalamic Nucleus/metabolism , Adrenomedullin , Nitric Oxide/metabolism , Rats, Sprague-Dawley , Receptors, GABA/metabolism , Bicuculline/metabolism , Bicuculline/pharmacology , Obesity/complications , Reflex/physiology , Blood Pressure/physiology , Nitric Oxide Synthase Type I/metabolism , Nitric Oxide Synthase Type I/pharmacology , gamma-Aminobutyric Acid/metabolism , gamma-Aminobutyric Acid/pharmacology , Sympathetic Nervous SystemABSTRACT
This study aimed to determine whether adrenomedullin (ADM, 7.2 µg/kg/day, ip), an important endogenous active peptide, has a protective role in cardiac remodeling and function in obesity-related hypertension (OH) rats. A high-fat diet (HFD) was used to induce OH for 20 weeks. H9c2 cells incubated with palmitate (PA, 200 µM) to mimic high free fatty acid in obesity were used as an in vitro model. In OH rats, ADM not only decreased body weight (BW) and blood pressure (BP) but also improved systemic inflammation and oxidative stress. Moreover, ADM still had a greater inhibitory effect on local inflammation and oxidative stress in the hearts of OH rats, and the same anti-inflammatory and antioxidant effects were also confirmed in PA-treated H9c2 cells. The ADM receptor antagonist or Akt inhibitor effectively attenuated the inhibitory effects of ADM on inflammation and oxidative stress in PA-stimulated H9c2 cells. Furthermore, ADM application effectively normalized heart function, and hematoxylin-eosin and Masson staining and collagen volume fraction results showed that ADM improved cardiac remodeling in hearts of OH rats. ADM attenuated cardiac inflammation and oxidative stress via the receptor-Akt pathway, which involves the improvement of cardiac remodeling and function in OH rats.
ABSTRACT
AIMS: White adipose tissue (WAT) dysfunction has been associated with adipose tissue low-grade inflammation and oxidative stress leading to insulin resistance (IR). Adrenomedullin (ADM), an endogenous active peptide considered as an adipokine, is associated with adipocytes function. METHODS: We evaluated the protective effects of ADM against IR in 3T3-L1 adipocytes treated by palmitic acid (PA) and in visceral white adipose tissue (vWAT) of obese rats fed with high-fat diet. RESULTS: We found that endogenous protein expressions of ADM and its receptor in PA-treated adipocytes were markedly increased. PA significantly induced impaired insulin signaling by affecting phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) axis and glucose transporter-4 (GLUT-4) levels, whereas ADM pretreatment enhanced insulin signaling PI3K/Akt and GLUT-4 membrane protein levels, decreased pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß) and IL-6 levels, and improved oxidative stress accompanied with reduced reactive oxygen species (ROS) levels and increased anti-oxidant enzymes manganese superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx1) and catalase (CAT) protein expressions. Furthermore, ADM treatment not only improved IR in obese rats, but also effectively restored insulin signaling, and reduced inflammation and oxidative stress in vWAT of obese rats. CONCLUSIONS: This study demonstrates a prevention potential of ADM against obesity-related metabolic disorders, due to its protective effects against IR, inflammation and oxidative stress in adipocytes.
Subject(s)
Insulin Resistance , Proto-Oncogene Proteins c-akt , Adipocytes/metabolism , Adrenomedullin/metabolism , Adrenomedullin/pharmacology , Animals , Inflammation/metabolism , Insulin/metabolism , Obesity/metabolism , Palmitic Acid/pharmacology , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinase/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RatsABSTRACT
BACKGROUND: Arterial medial calcification (AMC) is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes and chronic kidney disease. Here, we tested whether hydrogen sulfide (H2S) can prevent AMC in rats with diabetic nephropathy (DN). METHODS: DN was induced by a single injection of streptozotocin and high-fat diet (45% kcal as fat) containing 0.75% adenine in Sprague-Dawley rats for 8 weeks. RESULTS: Rats with DN displayed obvious calcification in aorta, and this was significantly alleviated by Sodium Hydrosulfide (NaHS, a H2S donor, 50 µmol/kg/day for 8 weeks) treatment through decreasing calcium and phosphorus content, ALP activity and calcium deposition in aorta. Interestingly, the main endogenous H2S generating enzyme activity and protein expression of cystathionine-γ-lyase (CSE) were largely reduced in the arterial wall of DN rats. Exogenous NaHS treatment restored CSE activity and its expression, inhibited aortic osteogenic transformation by upregulating phenotypic markers of smooth muscle cells SMα-actin and SM22α, and downregulating core binding factor α-1 (Cbfα-1, a key factor for bone formation), protein expressions in rats with DN when compared to the control group. NaHS administration also significantly reduced Stat3 activation, cathepsin S (CAS) activity and TGF-ß1 protein level, and improved aortic elastin expression. CONCLUSIONS: H2S may have a clinical significance for treating AMC in people with DN by reducing Stat3 activation, CAS activity, TGF-ß1 level and increasing local elastin level.
Subject(s)
Aorta/drug effects , Aortic Diseases/prevention & control , Diabetic Nephropathies/drug therapy , Hydrogen Sulfide/pharmacology , Tunica Media/drug effects , Vascular Calcification/prevention & control , Animals , Aorta/metabolism , Aorta/pathology , Aortic Diseases/etiology , Aortic Diseases/metabolism , Aortic Diseases/pathology , Cathepsins/metabolism , Diabetic Nephropathies/complications , Diabetic Nephropathies/metabolism , Disease Models, Animal , Elastin/metabolism , Male , Rats, Sprague-Dawley , STAT3 Transcription Factor/metabolism , Transforming Growth Factor beta1/metabolism , Tunica Media/metabolism , Tunica Media/pathology , Vascular Calcification/etiology , Vascular Calcification/metabolism , Vascular Calcification/pathologyABSTRACT
Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to improve glycemic control. This study was designed to investigate the effects of SGLT2i dapagliflozin (dapa) on cardiomyopathy induced by isoproterenol (ISO) and its potential mechanisms. Fifty male Sprague Dawley rats were randomly assigned to the control (n=10) and the ISO (2.5 mg/kg/day)-treated groups (n=40). After 2 weeks, the 28 surviving rats with obvious left ventricular dysfunction in the ISO group were randomized into three medication groups, including the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan group (S/V, n=9), the dapa group (n=9), and the ISO group (n=10) for 4 weeks. Next, electrical programmed stimulation was performed in all the groups to evaluate their susceptibility to ventricular arrhythmias (VAs). Compared to the ISO rats, the dapa administration not only effectively reduced the cumulative risk of death, the myocardial fibrosis, the plasma angiotensin II levels and its functional receptor AT1R protein expressions in the heart, and the proinflammatory cytokine levels in the cardiac tissue of the ISO-treated rats, but it also improved their cardiac function and inhibited oxidative stress. These effects were similar to S/V. However, dapa showed a greater efficacy than S/V in reducing the left ventricular end-diastolic volumes, lowing the heart rates and VAs, and decreasing the body weights and plasma glucose levels. The mechanisms by which dapa exerts protective effects on cardiomyopathy may be related to its indirect antioxidant capacity and direct hypoglycemic action.
ABSTRACT
Accumulating evidence has demonstrated that circular RNAs (circRNAs) are involved in the pathogenesis of cancer, including that of esophageal squamous cell carcinoma (ESCC). The current study aimed to investigate the role of hsa_circ_0000700 in ESCC. hsa_circ_0000700, miR-1229, and related functional gene expression was measured by RT-qPCR. To characterize the functions of hsa_circ_0000700 and miR-1229, ESCC cells were infected with hsa_circ_0000700-specific siRNA, miR-1229 mimics, and an inhibitor alone or in combination. Cell Counting Kit-8 (CCK8), colony formation, EdU, flow cytometry, and Transwell assays were employed to evaluate cell proliferation, apoptosis, and migration. Luciferase reporter and RNA immunoprecipitation assays were used to confirm the targeting relationship between hsa_circ_0000700 and miR-1229. Finally, a competing endogenous RNAs (ceRNA) network was built for hsa_circ_0000700, and miR-1229 targets were analyzed by bioinformatics. circ_0000700 expression was significantly upregulated in ESCC cell lines. Actinomycin D and RNase R treatment confirmed that circ_0000700 was more stable than its linear CDH9 mRNA form. Moreover, a cytoplasmic and nuclear fractionation assay suggested that circ_0000700 was mainly distributed in the cytoplasm of ECA-109 and TE-1 cells. In vitro, the proliferative and migratory capacities of ECA-109 and TE-1 cells were inhibited by knocking down circ_0000700 expression. Additionally, miR-1229 silencing reversed the circ_0000700-specific siRNA-induced attenuation of malignant phenotypes. Mechanistically, circ_0000700 was identified as a sponge of miR-1229 and could activate PRRG4, REEP5, and PSMB5 indirectly to promote ESCC progression. In summary, our results suggest that hsa_circ_0000700 functions as an oncogenic factor by sponging miR-1229 in ESCC.
ABSTRACT
OBJECTIVE: Adrenomedullin (ADM) possesses therapeutic potential for inflammatory diseases. Consequently, the effects of ADM on inflammation in visceral white adipose tissue (vWAT) of obese rats or in adipocytes were explored in this study. METHODS: Male rats were fed a high-fat diet for 12 weeks to induce obesity, and obese rats were implanted with osmotic minipumps providing constant infusion of ADM (300 ng/kg per hour) and continued to be fed a high-fat diet for 4 weeks. RESULTS: When compared with the control group, endogenous protein expression of ADM and ADM receptors in vWAT and in lipopolysaccharide (LPS)-treated adipocytes was markedly increased. ADM significantly decreased the protein expression of the inflammatory mediators TNFα, IL-1ß, cyclooxygenase-2, and inducible nitric oxide synthase in vWAT of obese rats and in adipocytes stimulated by LPS. It also inhibited the activation of the inflammatory signaling pathways MAPK and NF-κB induced by LPS in adipocytes. These effects of ADM in adipocytes were inhibited by the administration of ADM receptor antagonist and cAMP-dependent protein kinase (PKA) activation inhibitor. CONCLUSIONS: ADM can inhibit inflammation in WAT in obesity, which may be mediated by the activation of ADM receptors and PKA.
Subject(s)
Adipose Tissue, White/metabolism , Adrenomedullin/metabolism , Inflammation Mediators/metabolism , 3T3 Cells , Adipocytes/metabolism , Animals , C-Reactive Protein/analysis , Cyclooxygenase 2/metabolism , Diet, High-Fat , Inflammation/metabolism , Interleukin-1beta/metabolism , Male , Mice , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Obesity/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Adrenomedullin/antagonists & inhibitors , Signal Transduction , Tumor Necrosis Factor-alpha/bloodABSTRACT
Inflammation plays a critical role in the development of neurodegenerative diseases. Adrenomedullin 2 (AM2), a member of the calcitonin gene-related peptide family, has been known to have anti-inflammatory effects. Here, we evaluated the anti-inflammatory effects of AM2 in LPS-activated microglia and BV2 cells. The endogenous mRNA and protein expressions of AM2, calcitonin receptor-like receptor (CLR), receptor activity-modifying proteins (RAMPs) including RAMP1, RAMP2 and RAMP3 and the production of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by RT-PCR and Western blot. Our results revealed that LPS (1 µg/mL) significantly stimulated CLR, RAMP1, RAMP2 and RAMP3 protein expressions in BV2 microglia cells, but AM2 had a significant decrease. However, the mRNA levels of AM2, CLR, and RAMP1/2/3 were all markedly increased. LPS also induced obvious increases in mRNA and protein levels of the inflammatory mediators (TNF-α, IL-1ß, COX2 and iNOS). More importantly, AM2 (10 nM) administration effectively inhibited the mRNA and protein expressions of these mediators induced by LPS and increased the cAMP content in LPS-stimulated BV2 cells. Furthermore, the antagonism with AM2 receptor antagonist IMD17-47, adrenomedullin (AM) receptor antagonist by AM22-52 or the inhibition of protein kinase A (PKA) activation by P1195 effectively prevented the inhibitory role of AM2 in LPS-induced production of the above inflammatory mediators. In conclusion, AM2 inhibits LPS-induced inflammation in BV2 microglia cells that may be mainly through AM receptor-mediated cAMP-PKA pathway. Our results indicate AM2 plays an important protective role in microglia inflammation, suggesting therapeutic potential for AM2 in neuroinflammation diseases caused by activated microglia.
Subject(s)
Inflammation/metabolism , Microglia/metabolism , Signal Transduction , Animals , Cells, Cultured , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Inflammation Mediators/metabolism , Lipopolysaccharides/administration & dosage , Rats, Sprague-Dawley , Receptors, Cyclic AMP/metabolismABSTRACT
BACKGROUND: The adipose afferent reflex (AAR), a sympatho-excitatory reflex, can promote the elevation of sympathetic nerve activity (SNA) and blood pressure (BP). Inflammation in the paraventricular nucleus (PVN) involves sympathetic abnormality in some cardiovascular diseases such as hypertension. This study was designed to explore the effects of tumor necrosis factor alpha (TNFα) in the PVN on the AAR and SNA in rats with obesity-related hypertension (OH) induced by a high-fat diet for 12 weeks. METHODS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded in anesthetized rats, and their responses to capsaicin (CAP) stimulation of the right inguinal white adipose tissue were used to evaluate the AAR. RESULTS: Compared to the control rats, the systolic blood pressure (SBP), plasma norepinephrine (NE, indicating SNA) and TNFα levels, TNFα mRNA and protein levels, reactive oxygen species (ROS) content and NADPH oxidase activity in the PVN were significantly elevated in rats with OH. TNFα in the PVN markedly enhanced sympathoexcitation and AAR. Moreover, the enhancement of AAR caused by TNFα can be significantly strengthened by the pretreatment of diethyldithiocarbamate (DETC), a superoxide dismutase inhibitor, but attenuated by TNF-α receptor antagonist R-7050, superoxide scavenger PEG-SOD and NADPH oxidase inhibitor apocynin (Apo) in rats with OH. Acute microinjection of TNF-α into the PVN significantly increased the activity of NADPH oxidase and ROS levels in rats with OH, which were effectively blocked by R-7050. Furthermore, our results also showed that the increased levels of ROS, TNFα and NADPH oxidase subunits mRNA and protein in the PVN of rats with OH were significantly reversed by pentoxifylline (PTX, 30 mg/kg daily ip; in 10% ethanol) application, a cytokine blocker, for a period of 5 weeks. PTX administration also significantly decreased SBP, AAR and plasma NE levels in rats with OH. CONCLUSIONS: TNFα in the PVN modulates AAR and contributes to sympathoexcitation in OH possibly through NADPH oxidase-dependent ROS generation. TNFα blockade attenuates AAR and sympathoexcitation that unveils TNFα in the PVN may be a possible therapeutic target for the intervention of OH.
Subject(s)
Adipose Tissue/metabolism , Diet, High-Fat , Obesity/metabolism , Paraventricular Hypothalamic Nucleus/metabolism , Tumor Necrosis Factor-alpha/metabolism , Adipose Tissue, White/pathology , Adiposity , Animals , Body Weight , Inflammation/metabolism , Male , NADPH Oxidases/metabolism , Neurons, Afferent/metabolism , Norepinephrine/blood , Rats , Rats, Inbred SHR , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Sympathetic Nervous System/pathology , Systole , Tumor Necrosis Factor-alpha/bloodABSTRACT
OBJECTIVE: To study the prevalence of atrial fibrillation (AF) and the relation with its risk factors in China. METHODS: A total of 19 363 participants (8635 males and 10 728 females) aged â35 years in geographically dispersed urban and rural regions of China were included in this cross-sectional survey. All participants received questionnaire, physical and blood examination. Echocardiography were performed for AF patients found in the survey. RESULTS: Of the 19 363 participants, 199 were diagnosed with AF. The estimated age-standardized prevalence of AF was 0.78% in men and 0.76% in women. The prevalence of AF in participants aged <60 years was 0.41% in men and 0.43% in women, and was 1.83% in both men and women aged â60 years. About 19.0% of males and 30.9% of females with AF were diagnosed with valve disease. Age- and sex-adjusted multivariable logistic regression analysis revealed that myocardial infarction, left ventricular hypertrophy (LVH), obesity, and alcohol consumption were associated with a increased risk of AF(P<0.05). CONCLUSION: The age standardized prevalence of AF is 0.77% in the participants enrolled in the present study. The number of AF cases aged â35 years is 5.26 million according to 2010 Chinese Census. Most risk factors for AF, identified mainly in Western countries, are also detected in China.
Subject(s)
Atrial Fibrillation/epidemiology , Adult , China/epidemiology , Female , Humans , Male , Prevalence , Risk Factors , Rural Population , Urban PopulationABSTRACT
BACKGROUND: Non-valvular atrial fibrillation is associated with an increased risk of ischemic stroke; however, the appropriate intensity of anticoagulation therapy for Chinese patients has not been determined. The purpose of this study was to compare the safety and the efficacy of standard-intensity warfarin therapy, low-intensity warfarin therapy, and aspirin therapy for the prevention of ischemic events in Chinese patients with non-valvular atrial fibrillation (NVAF). METHODS: A total of 786 patients from 75 Chinese hospitals were enrolled in this study and randomized into three therapy groups: standard-intensity warfarin (international normalized ratio (INR) 2.1 to 2.5) group, low-intensity warfarin (INR 1.6 to 2.0) group and aspirin (200 mg per day) group. All patients were evaluated by physicians at 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after randomization to obtain a patient questionnaire, physical examination and related laboratory tests. RESULTS: The annual event rates of ischemic stroke, transient ischemic attack (TIA) or systemic thromboembolism were 2.6%, 3.1% and 6.9% in the standard-intensity warfarin, low-intensity warfarin and aspirin groups, respectively (P = 0.027). Thromboembolic event rates in both warfarin groups were significantly lower than that in the aspirin group (P = 0.018, P = 0.044), and there was no significant difference between the two warfarin groups. Severe hemorrhagic events occurred in 15 patients, 7 (2.6%) in the standard-intensity warfarin group, 7 (2.4%) in the low-intensity warfarin group and 1 (0.4%) in the aspirin group. The severe hemorrhagic event rates in the warfarin groups were higher than that in the aspirin group, but the difference did not reach statistical significance (P = 0.101). The mild hemorrhagic and total hemorrhagic event rates in the warfarin groups (whether in the standard-intensity warfarin group or low-intensity warfarin group) were much higher than that in the aspirin group with the annual event rates of total hemorrhages of 10.2%, 7.6% and 2.2%, respectively, in the 3 groups (P = 0.001). Furthermore, there was no significant difference in all cause mortality among the three study groups. CONCLUSION: In Chinese patients with NVAF, the warfarin therapy (INR 1.6 - 2.5) for the prevention of thromboembolic events was superior to aspirin.
Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Aspirin/administration & dosage , Aspirin/therapeutic use , Female , Humans , Male , Middle Aged , Warfarin/administration & dosage , Warfarin/therapeutic useABSTRACT
BACKGROUND: P-wave dispersion (PWD) is a useful predictor of paroxysmal atrial fibrillation (AF). The effect of cardiac resynchronization therapy (CRT) on PWD and the prognostic implications of the improvement in PWD remain undefined. The aim of the study was to explore the clinical significance of the improvement of PWD after CRT. METHODS: Electrocardiographic studies were performed before and three months after CRT in 81 patients (57 men and 24 women; age (60.5 ± 11.2) years) with standard CRT indication but no history of AF. A significant improvement of PWD (PWD responder) was defined as a relative decrease ≥ 20% from baseline PWD. The primary endpoints were new-onset AF detected by electrocardiogram (ECG) or CRT. RESULTS: After (30.6 ± 7.5) months of follow-up, PWD responders (n = 43) had a significantly lower incidence of AF than did PWD nonresponders, 12% vs. 29% (P < 0.001). In Cox proportional hazard analysis, PWD responders was the only predictor of lower risk of new-onset AF (HR 0.33, 95% confidence interval 0.12 - 0.96, P = 0.033). CONCLUSION: Improvement of P-wave dispersion after CRT was associated with a lower incidence of AF, which may be related to the significant improvement in left ventricular systolic function and the reverse modeling of the left atrium.
Subject(s)
Atrial Fibrillation/prevention & control , Cardiac Resynchronization Therapy , Electrocardiography , Heart Failure/therapy , Adult , Aged , Echocardiography , Female , Heart Failure/physiopathology , Humans , Male , Middle AgedABSTRACT
BACKGROUND: The Medtronic InSync Sentry is the first available cardiac resynchronization therapy defibrillator (CRT-D) which can monitor fluid status by measuring intrathoracic impedance. This study was designed to observe the effectiveness of intrathoracic impedance monitoring on detecting aggravation of heart failure. METHODS: We retrospectively analyzed the clinical data of 14 consecutive patients. Patients were regularly followed up every 3 - 6 months after the implantation. At each visit, interrogation of the device was done. Patients were instructed to inform the researcher on hearing the device alert, and to take extra 40 milligrams of furosemidum if they had aggravated symptoms later. If the symptoms could not be relieved, they were asked to see a doctor. Data about heart failure hospitalization were collected from the medical record. RESULTS: During 18 - 48 months follow-up, a total of 7 patients encountered 28 alert events. On one hand, alert events appeared before all deteriorated symptoms and heart failure hospitalizations. On the other hand, there were 23 alerts followed by deterioration of heart failure symptoms, and 2 alerts related to 2 hospitalizations caused by pulmonary infection in one patient. Only 5 patients were hospitalized 10 times for deterioration of cardiac function. CONCLUSION: The function of intrathoracic impedance monitoring is reliable in predicting deterioration of heart failure.
Subject(s)
Cardiography, Impedance/methods , Heart Failure/pathology , Adult , Aged , Aged, 80 and over , Cardiac Resynchronization Therapy , Female , Heart Failure/therapy , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Although cardiac resynchronization therapy (CRT) is already an established treatment, the characteristics of patients who have an excellent response to CRT and those who get no benefit remain to be determined. The purpose of this study was to search for potential predictors of both non-response and super-response to CRT. METHODS: Seventy-six consecutive patients who received CRT treatment were divided into group A (non-responders), group C (super-responders) and group B (responders exclusive of super-responders). Student's t test, Mann-Whitney test, Logistic regression and receiver operating characteristic curve were employed to identify potential predictors among the patients' demographic characteristics, clinical features, several electrocardiographic parameters before and after CRT implantation, and their pre-implant echocardiographic parameters. RESULTS: Group A had the lowest 3-month left ventricular ejection fraction (LVEF). Group C had the smallest pre-implant left ventricular end-diastolic dimension (LVEDD), the shortest post-implant QRS duration, the smallest 3-month LVEDD and the highest 3-month LVEF. In addition, there was a trend of gradual change in percent of left bundle branch block, severity of pre-implant mitral regurgitation, pre-implant QRS dispersion, post-implant QRS duration as well as post-implant QRS dispersion from group A to group B and from group B to group C. Multivariable Logistic analysis revealed that only pre-implant LVEDD could predict CRT super-response. A pre-implant LVEDD of 68.5 mm was the cut-off value that identified super-responders with 87.5% sensitivity and 79.7% specificity. A pre-implant LVEDD of 62.5 mm identified super-responders with 50.0% sensitivity and 89.8% specificity. CONCLUSIONS: Predictors of a CRT non-response remain unclear at present. But it is credible that patients with a smaller left ventricle would have a better chance to become super-responders to CRT.
Subject(s)
Cardiac Resynchronization Therapy , Aged , Echocardiography , Electrocardiography , Female , Heart Failure/therapy , Heart Ventricles , Humans , Male , Middle AgedABSTRACT
A 62-year-old woman with frequent occurrence of symptomatic atrial tachycardia with a foci located at the root of the upper crista terminalis was found to have right diaphragm paresis after receiving a total of 8 radiofrequency energy deliveries (40-60 W, 50-60ºC) and a total duration of 540 seconds of ablation therapy (7Fr 8 mm deflectable ablation catheter). The right diaphragm paresis remained resolved up to 14 months after the procedure as confirmed by repeated chest X-rays.
Subject(s)
Catheter Ablation/adverse effects , Diaphragm/injuries , Tachycardia, Supraventricular/therapy , Female , Humans , Middle AgedABSTRACT
OBJECTIVE: To evaluate the value of 64-slice computed tomography (MDCT) in previsualization the cardiac veins anatomy before the implantation of cardiac resynchronization therapy (CRT). METHODS: The 64-slice CT scans of 21 patients [10 men, age (61.6 ± 9.7) years] were obtained and analyzed before the implantation of CRT. Retrograde coronary venography was performed during intraoperational fluoroscopy. The coronary sinus (CS) and the main tributaries were measured. RESULTS: Similar images to those obtained during the CRT implantation procedure were obtained by MDCT in 71% of the patients. The coronary sinus was clearly visible in all cases, the measured ostium was (12.1 ± 4.2) mm, and the angle between the CS and the vertical plane was (99 ± 12) degrees. In 90% of patients, at least one vein was clearly visible in the target area. Among the target veins, the posterolateral vein was visible in most cases (86%) and the lateral vein was visible in 48% of the patients. CONCLUSION: MDCT is an effective and noninvasive method for previsualization of the cardiac venous system, which may facilitate optimal left ventricular lead positioning for CRT implantation.
Subject(s)
Cardiac Resynchronization Therapy , Heart Failure/diagnostic imaging , Heart Failure/therapy , Aged , Cardiac Pacing, Artificial , Coronary Angiography , Female , Humans , Male , Middle Aged , Tomography, Spiral ComputedABSTRACT
BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation are the main reasons causing sudden cardiac death. This study aimed to investigate the effects of nifekalant hydrochloride (NIF) on QT dispersion (QTd) in treating VT. METHODS: A total of 16 consecutive patients suffered sustained VT was included and then randomly divided into two groups according to the administration duration of NIF. In long-time group (group L), patients were injected with NIF continuously for at least 12 hours after a bolus dose. The patients in short-time group (group S) were injected with NIF just for 1 hour. RESULTS: There were 7 of all 10 episodes of VT which were terminated by NIF, including 4 episodes in group L were stopped over 1 hour after continuous infusion of NIF. One patient suffered from torsade de pointes. Electrocardiography analysis indicated that QTd was significantly decreased 12 hours after stopping of infusing NIF compared with that when VT stopped ((45.4 +/- 22.1) ms vs. (73.4 +/- 33.2) ms, P < 0.01), and the corrected QTd (QTcd) decreased too ((47.8 +/- 22.9) ms vs. (78.3 +/- 36.5) ms, P < 0.01). There was a positive correlation between the increase in QTd and dose of administrating NIF (P < 0.01), so was QTcd (P < 0.01). CONCLUSIONS: More administration of NIF indicates higher terminating rate of VT and more QTd prolongation. However, the safety is acceptable if several important issues were noticed in using NIF, such as serum potassium concentration, stopping side-effect related agents, and carefully observing clinical responses.
Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Long QT Syndrome/drug therapy , Pyrimidinones/therapeutic use , Tachycardia, Ventricular/drug therapy , Adult , Electrocardiography , Female , Humans , Long QT Syndrome/pathology , Male , Middle Aged , Tachycardia, Ventricular/pathology , Treatment OutcomeABSTRACT
OBJECTIVE: To analyse the reasons for pacing lead abandonment during pacemaker replacement. METHOD: Clinical data of patients underwent permanent pacemaker replacement between Jan 1st, 1976 to Dec 31st 2006 in Fuwai Hospital were obtained and the reasons for pacing leads abandonment were analyzed. RESULTS: Pacemaker was replaced in 1023 patients during this period and 235 pacing leads were abandoned, 131 leads (55.7%) were abandoned for leads malfunction, including leads body fracture (35, 14.9%), isolation defects (10, 4.3%), dislocations (10, 4.3%) and excessively high threshold values (76, 32.3%). Other reasons for leads abandonment were infection (50, 21.3%), incompatibility between the leads and new generator (30, 12.8%), need to degrade the pacing system (13, 5.5%) and other rare reasons (11, 4.7%). CONCLUSION: The most often reason for leads abandonment during pacemaker replacement is lead malfunction, including lead body fracture, isolation defect, dislocation and excessively high threshold value of the leads.