Adrenomedullin Improves Hypertension and Vascular Remodeling partly through the Receptor-Mediated AMPK Pathway in Rats with Obesity-Related Hypertension.

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.

Hydrogen sulfide prevents arterial medial calcification in rats with diabetic nephropathy.

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.

Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats.

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.

Adrenomedullin improved endothelial dysfunction via receptor-Akt pathway in rats with obesity-related hypertension.

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.

Prevalence of atrial fibrillation in China and its risk factors.

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 ⋝35 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 ⋝60 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 ⋝35 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.

Adrenomedullin in paraventricular nucleus attenuates adipose afferent reflex and sympathoexcitation via receptors mediated nitric oxide-gamma-aminobutyric acid A type receptor pathway in rats with obesity-related hypertension.

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.

Adrenomedullin ameliorates palmitic acid-induced insulin resistance through PI3K/Akt pathway in adipocytes.

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.

Adrenomedullin Improves Cardiac Remodeling and Function in Obese Rats with Hypertension.

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.

Adrenomedullin 2 attenuates LPS-induced inflammation in microglia cells by receptor-mediated cAMP-PKA pathway.

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.

Circular RNA hsa_circ_0000700 promotes cell proliferation and migration in Esophageal Squamous Cell Carcinoma by sponging miR-1229.

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.

The cardioprotective effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in rats with isoproterenol-induced cardiomyopathy.

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.

Adrenomedullin Attenuates Inflammation in White Adipose Tissue of Obese Rats Through Receptor-Mediated PKA Pathway.

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.

[Usefulness of previsualization of the cardiac venous system by 64-slice computed tomography in patients with heart failure underwent cardiac resynchronization therapy].

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.

Inflammation in lone atrial fibrillation.

OBJECTIVES: This study was designed to evaluate the correlation between lone atrial fibrillation and inflammation. METHODS: A total of 411 subjects were enrolled in this study, including 333 patients with lone atrial fibrillation, and 78 controls. C-reactive protein (CRP) and echocardiography were evaluated, and the electrocardiograph was monitored to identify cardiac rhythm at the time of blood sampling. According to the rhythm, paroxysmal atrial fibrillation was divided into presence and absence of atrial fibrillation. RESULTS: Subjects with lone atrial fibrillation had higher CRP levels than controls (media, 1.00 mg/L; IQR, 1.00-2.54 versus media, 1.00 mg/L; IQR, 1.00-1.55; p = 0.016) and subjects with persistent atrial fibrillation had higher CRP levels than those with paroxysmal atrial fibrillation (media, 1.62 mg/L; IQR, 1.00-3.98 versus media, 1.00 mg/L, IQR, 1.00-2.10; p = 0.022), and so did presence of atrial fibrillation rather than absence of atrial fibrillation (media, 2.11 mg/L; IQR, 1.00-3.60 versus media, 1.00 mg/L; IQR, 1.00-1.76; p = 0.000) in paroxysmal atrial fibrillation. However, there was no significant difference in CRP levels between persistent atrial fibrillation and presence of atrial fibrillation in paroxysmal atrial fibrillation (p = 0.992). Neither was there any difference between absence of atrial fibrillation in paroxysmal atrial fibrillation and controls (p = 0.483). In patients with lone atrial fibrillation, atrial fibrillation rhythm (B = 4.85, 95%CI: 2.61-8.99) was the only independent predictor of elevated CRP levels after adjusted covariants. CONCLUSIONS: Patients with lone atrial fibrillation had elevated CRP levels only when they were in atrial fibrillation rhythm and an elevated CRP level was not related to duration of time or history of atrial fibrillation.

[A 10 years review of the characteristics of in-hospital ventricular fibrillation victim in a single center].

OBJECTIVE: To study the factors influencing the outcome of patients suffering from in-hospital ventricular fibrillation (IHVF), as there have been few studies focusing on this topic. METHODS: Patients with IHVF collected in a single cardiac center were classified into a successful group and a failure group. Data relevant to the predicting factors of the two groups were compared. RESULTS: There were 206 events in the analysis. The most common underlining disease was coronary artery disease (CAD), especially acute myocardial infarction (AMI). On multiple logistic regression analysis, it was shown that the independent predictors for failure of defibrillation were higher NYHA class (OR 1.7, 95% CI 1.3 - 2.2, P < 0.001), higher blood potassium level (OR 2.9, 95% CI 1.9 - 4.3, P = 0.007) and adrenaline usage (OR 25.0, 95% CI 11.5 - 55.1, P < 0.001). In a AMI sub-group, 56.9% of the IHVF events occurred within the first day of AMI, and the occurrence descended with time going on within 2 weeks. Before the occurrence of IHVF, the patients with right coronary artery as the infarction related artery (IRA) often suffered from (8/9, 88.9%) bradycardia (R-R interval > 1 s), but those with left anterior descending artery as IRA often showed (8/12, 66.7%) tachycardia (RR interval < 0.6 s). CONCLUSIONS: The common disease causing IHVF is CAD. The worse the heart function, the higher the rate of IHVF and the worse the prognosis. It IHVF not induced by hypokalemia and use of adrenaline in resuscitation predict lower successful defibrillation rate.

[Reasons for pacing leads abandonment during pacemaker replacement: a single center experience with 235 cases].

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.

[Efficacy of cardiac resynchronization therapy-defibrillator for treating patients with chronic heart disease].

OBJECTIVE: To observed the clinical efficacy of cardiac resynchronization therapy-defibrillator (CRT-D) in selected patients with chronic heart failure one year after implantation. METHODS: Seventeen patients with drug-refractory heart failure received CRT-D implantation (6 patients were implanted with InSync Sentry). The underlying heart diseases were dilated cardiomyopathy in 12 patients and ischemic heart disease in 5 patients. There were 13 patients with a history of ventricular tachycardia/ventricular fibrillation. RESULTS: CRT-D were successfully implanted in all patients without complication. The mean left ventricular pacing threshold was 1.6 V. The defibrillation threshold was no more than 20 J. During a mean follow-up of 13 months, no death occurred and LV function was improved. The shock induced by ventricular tachycardia was delivered in 5 patients and alarming due to heart failure occurred twice in 1 patient. CONCLUSIONS: The implantation of CRT-D for treating refractory heart failure patients is feasible and safe. The application of CRT-D was associated with an improved cardiac function and a reduced risk of sudden cardiac death.

[Clinical and ECG features of arrhythmogenic right ventricular cardiomyopathy: a retrospective analysis of 31 cases].

OBJECTIVE: To retrospectively analyze the clinical and electrocardiographic features of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: The clinical, electrocardiographic features and the efficacy of various therapies were analyzed in 31 patients (27 males) diagnosed as ARVC according to the criteria established by European Society of Cardiology. RESULTS: The averaged age when the ARVC was first diagnosed was (34.7 +/- 9.4) years (19 - 58 years), palpitation was present in 28 patients (90.3%) and syncope in 13 patients (41.9%), a family history of sudden death was present in 1 patient. Dilatated right ventricle was documented in 29 patients by echocardiography and (or) magnetic resonance imaging (MRI), 2 of them with dilated left ventricles. ECG changes included: T wave inversion, mostly seen in precordial leads (100%); epsilon (epsilon) wave (54.8%); QRS duration >or= 110 ms in V(1) to V(3) (83.9%); reduced extremity amplitude (41.9%); the first degree of AV block (22.6%); sustained VT (100%) including 15 monomorphic VT (48.4%) and 16 polymorphic VT (51.6%). The mean values of QRS duration in leads of V(1 - 3) [(120.8 +/- 13.7) ms] was significantly longer than that in V(4 - 6) [(99.4 +/- 13.7) ms, P < 0.05]. Fourteen patients underwent radiofrequency catheter ablation (RFCA) with an immediate success rate of 78.6% (11/14). During follow up (18.3 +/- 10.2) months, VT reoccurred in 6 patients (54.5%). The remaining 17 patients were treated with conventional medications, 7 of them were medicated under implanted cardioverter defibrillator (ICD). During the follow-up (35.6 +/- 19.0) months, VT reoccurred in 11 patients (64.7%) and one patient died suddenly. CONCLUSIONS: ARVC patients developed symptoms at mid-30s with significant ECG changes including appearance of an epsilon wave, T wave inversion and QRS duration >or= 110 ms in leads of V(1 - 3). The long term therapy efficacy was not satisfactory both for RFCA and conventional medications and ICD implantation should be recommended to patients with ARVC.

Complications of cardiac resynchronization therapy in patients with congestive heart failure.

BACKGROUND: Previous clinical studies have suggested that patients with congestive heart failure and intraventricular conduction delay could benefit from cardiac resynchronization therapy (CRT). Implantation of left ventricular lead is a complex procedure with some potential for complications. This study was conducted to analyse the complications of CRT in patients with congestive heart failure. METHODS: Totally 117 patients, 86 males and 31 females, mean age of 53 years, with congestive heart failure and intraventricular conduction delay were enrolled in this study. Venography was performed on all patients. Different types of coronary sinus leads were used to pace the left ventricle. RESULTS: Left ventricular lead was attempted to implant through coronary sinus for all the 117 patients and was successfully implanted in 111 patients. The success rate was 94.9%. Main complications rate was 6.8%, including coronary sinus dissection in 4 patients, phrenic nerve stimulation required lead repositioning in 2 patients and lead dislodgement in 2 patients. CONCLUSIONS: It is feasible and safe to pace left ventricle through coronary sinus. However, there are some procedural complications.

Incidence and causes of inappropriate detection and therapy by implantable defibrillators of cardioversion in patients with ventricular tachyarrhythmia.

BACKGROUND: Implantable cardioverter defibrillator (ICD) is the only effective therapy in patients with life threatening ventricular arrhythmias. Inappropriate detection and therapy by ICDs are the most common causes of side effects that affect the quality of life in ICD recipients. This study evaluated the incidence and causes of inappropriate detection and therapy by ICDs in patients in our hospital. METHODS: From January 2000 to December 2005, fifty patients who received ICD implantation for ventricular arrhythmias for prevention of sudden cardiac death were evaluated in this study. Each ICD was programmed using clinical arrhythmic and cardiac data of the patient before discharge. Patients were followed up by standard schedule after implantation and all data retrieved from each device were collected and saved for further analysis. RESULTS: No arrhythmic event was detected in 12/50 (24%) patients during the period of follow-up. Among the remaining patients, 11 (22%) experienced inappropriate detections and therapies during follow-up in this study. ICD detected 383 ventricular tachyarrhythmia (VT) and 108 ventricular fibrillation (VF) episodes and delivered 678 therapies. In VT group, ICD delivered 413 antitachycardiac pacings (ATPs) and 118 shocks, among which 78 ATPs and 9 shocks were initiated by 55/383 (14.3%) inappropriate detections. In VF group ICD delivered 147 shocks, among which 56 shocks were initiated by 28/108 (26.9%) inappropriate detections. Overall, more than 50% of these episodes were caused by atrial fibrillation (AF) with rapid ventricular response, followed by electromagnetic or myopotential interference. In addition, most inappropriate therapies occurred within one year after ICD implantation. CONCLUSIONS: About one fifth of patients experienced ICD inappropriate detection and therapy after implantation. The main cause was AF with rapid ventricular response, followed by electromagnetic or myopotential interference.