Quality control of the blood pressure phenotype in the Gaoyou population study.

The Korotkoff approach is the only blood pressure (BP) measurement technique that allows contemporary data to be compared with decades of research. We randomly recruited 4483 people (53.3% women; mean age 52.1 years) from Gaoyou County, Jiangsu Province, China. Nine observers recorded the participants™ BP three times consecutively following Chinese Society of Hypertension guidelines. We assessed the BP phenotype based on five criteria: completeness of readings, percentage of identical BP readings, odd BP readings, end-digit preference and trends in BP from the first to the third reading. The proportion of participants with identical readings were 2.0% and 3.1% for systolic (SBP) and diastolic blood pressure (DBP), respectively. Among 26,898 BP values, 0.3% ended in an odd number. Among observers, the prevalence of identical readings varied from 0% to 5.3% for SBP and from 0% to 6.8% for DBP. Compared with the expected frequency of 20%, those ending in 0 had a lower frequency (17.2%; p < 0.001), whereas those ending in 8 had a higher frequency (22.4%; p < 0.001). From the first to the third measurement, SBP and DBP decreased (p < 0.001) by 0.87 and 0.55 mmHg, respectively. In conclusion, the procedures set up in the Gaoyou study produced a high-quality BP phenotype.

Hypertension related knowledge and behaviour associated with awareness, treatment and control of hypertension in a rural hypertensive population: a community based, cross-sectional survey.

BACKGROUND AND OBJECTIVE: Hypertension-related knowledge and behaviour have been identified as influential factors associated with awareness, treatment and control of hypertension in urban regions. However, there were few studies on rural areas. This study aims to investigate whether hypertension related knowledge and behaviour were associated with hypertension awareness, treatment and control in Gaoyou, a rural area of Jiangsu province, China. METHODS: A cross-sectional, population-based survey was conducted among hypertensive individuals in rural areas of Gaoyou, the south-eastern of China in 2010. We identified 1943 subjects with hypertension among 4536 subjects participated in this study and collected information about medical history, use of medication, hypertension related knowledge and behaviour by a standardized questionnaire. RESULTS: This study showed that 41.07% of subjects were aware of their disease, 30.01% of subjects were taking antihypertensive medication and 5.04% of subjects controlled their blood pressure. Multivariate logistic regression analysis showed that subjects who knew the threshold, the lifelong treatment of hypertension and measured blood pressure at least once a year had better detection, treatment or control of hypertension. CONCLUSION: Hypertension related knowledge and behaviour were associated with awareness, treatment and control rate of hypertension in the rural areas of south-eastern China.

Emerging natural and tailored perovskite-type mixed oxides-based catalysts for CO2 conversions.

The rapid economic and societal development have led to unprecedented energy demand and consumption resulting in the harmful emission of pollutants. Hence, the conversion of greenhouse gases into valuable chemicals and fuels has become an urgent challenge for the scientific community. In recent decades, perovskite-type mixed oxide-based catalysts have attracted significant attention as efficient CO2 conversion catalysts due to the characteristics of both reversible oxygen storage capacity and stable structure compared to traditional oxide-supported catalysts. In this review, we hand over a comprehensive overview of the research for CO2 conversion by these emerging perovskite-type mixed oxide-based catalysts. Three main CO2 conversions, namely reverse water gas shift reaction, CO2 methanation, and CO2 reforming of methane have been introduced over perovskite-type mixed oxide-based catalysts and their reaction mechanisms. Different approaches for promoting activity and resisting carbon deposition have also been discussed, involving increased oxygen vacancies, enhanced dispersion of active metal, and fine-tuning strong metal-support interactions. Finally, the current challenges are mooted, and we have proposed future research prospects in this field to inspire more sensational breakthroughs in the material and environment fields.

An algorithm to predict the site of origin of focal atrial tachycardia.

BACKGROUND: Only a few algorithms for predicting the site of origin of focal atrial tachycardia (AT) have been reported. We aimed to develop a new and more effective algorithm. METHODS: Surface 12-lead electrocardiograms were collected during tachycardia and sinus rhythm in 61 patients who received successful radiofrequency ablation. P-wave polarities, durations, and amplitudes were analyzed. Predictive values of the most significant parameters were determined. An algorithm was then developed and prospectively evaluated in 30 new consecutive AT patients. RESULTS: Thirty-six percent (22/61) of the foci were located at the ostium of coronary sinus (CS). Other common foci included pulmonary veins (PVs, n = 15), right atrial appendage (RAA, n = 7), parahisian area (n = 7), and crista terminalis (CT, n = 3). Positive P waves in inferior leads (II, III, and aVF) and a negative P wave in lead aVR indicated high atrial origins (high CT, superior PVs, and RAA, defined as Area A), with a sensitivity of 95% and a specificity of 90%. Negative P waves in inferior leads and a positive P wave in lead aVR suggested right low septal origins (CS ostium and inferior tricuspid annulus, defined as Area B), with good sensitivity and specificity (88% and 89%, respectively). This new P-wave diagnostic algorithm correctly identified the site of origin in 90% of AT cases. CONCLUSION: Combination of data from multiple leads and regrouping of sites of origin provides a better predictive value.

[Impact of metoprolol use in the treatment of patients with electrical-storm after cardioverter defibrillators implantation].

OBJECTIVE: To explore the effectiveness of the metoprolol dosage adjustment on reducing the incidence of electrical-storm (ES) in patients with Implantable Cardioverter Defibrillators (ICDs). METHODS: Data from patients with ICD implantation between Jan, 2003 and Jun, 2006 in our hospital were retrospectively analyzed. ES was defined as either ≥ 3 times of ventricular tachyarrhythmias (VTAs) resulting in ICD therapy or VTAs lasting more than 30 s detected by ICD without any therapy within 24 hours. RESULTS: During a follow-up period of (27.5 ± 21.2) months, ES was recorded in 39 cases [34 males, average age (52.0 ± 13.1) years] out of 119 patients (32.8%) and 9 patients died after ES. During the period of storm attack, ES was successfully controlled in 25/30 patients by various interventions, including predisposing factors corrected in 5 cases, ICD reprogramming and antiarrhythmic drugs therapy optimized in 16 cases (one received intravenous injection of metoprolol), and VTAs eliminated by catheter ablation in 4 cases. ES was spontaneously resolved in the remaining 5 cases. In the chronic phase, 2 patients with Brugada syndrome were treated with Quinidine mono-therapy while the dosage of metoprolol was adjusted in the remaining 23 patients and the dosage of metoprolol was increased gradually from (26.8 ± 13.9) mg/d to (88.9 ± 53.5) mg/d without any adverse effects (9 patients received also oral amiodarone 200 mg/d). Post dosage adjustment, the total VTA episodes [(1.9 ± 1.7) times/month vs. (0.8 ± 0.6) times/month, P = 0.004], incidence of antitachycardia pacing therapies [(4.2 ± 3.8) runs/month vs. (2.3 ± 2.0) runs/month, P = 0.003], as well as electrical cardioversion or defibrillation [(1.1 ± 0.9) times/month vs. (0.4 ± 0.2) times/month, P = 0.001] were significantly decreased. ES was not controlled until a extremely high dosage [225 - 300 (255.3 ± 41.7) mg/d] of metoprolol was reached in the remaining 5 patients. CONCLUSIONS: Metoprolol use is essential and its dosage should be individualized in the majority of ICD recipients with ES. In approximately 1/6 patients, the dosage of metoprolol should be higher than 200 mg/d.

[Clinical characteristics of congenital ventricular aneurysm and diverticula in inland China].

OBJECTIVE: To summarize the clinical characteristics of congenital ventricular aneurysm and diverticula in inland China. METHODS: To identify the literature of congenital aneurysm and diverticula from Wanfang, China National Knowledge Infrastructure (CNKI) and PubMed databases, and to analyze the clinical characteristics of congenital aneurysm and diverticula from January of 2001 to December of 2009. RESULTS: A total of 116 patients [78 men, 1 - 80 (33.5 ± 21.3) years old] with congenital aneurysm or diverticula were included in 109 articles. Twenty-five patients (13 men) were congenital ventricular aneurysm, including a family of 4 patients. Ninety-one patients (65 men) were congenital ventricular diverticula. One hundred patients were detected by echocardiography during medical examination, 34 patients combined with other cardiac anomalies, 4 of which with extracardiac structures. There were 8 patients with ventricular arrhythmia, 8 patients with thrombosis, 2 patients died of cardiac rupture, 4 patients died of sudden death, surgical operation was performed in 46 patients and 3 patients received ablation procedure. All patient did not receive implantable cardioverter defibrillator (ICD) implantation. CONCLUSIONS: Congenital ventricular aneurysm or diverticulum is a rare cardiac malformation. Most congenital left ventricular aneurysms and diverticula are asymptomatic and detected by echocardiography. Congenital ventricular aneurysm or diverticulum may cause ventricular tachycardia, ventricular wall rupture, systemic embolization or sudden death, which had to be treated individually.

Premature ventricular contractions originating from the right ventricular outflow tract: three-dimensional distribution of the target sites and their electrocardiographic characteristics.

1. The purpose of the present study was to explore the relationship between electrocardiogram (ECG) patterns of right ventricular outflow tract (RVOT) premature ventricular contractions and the three-dimensional distribution of the target sites. 2. Thirty-three consecutive patients were included in the study. The target sites were identified by non-contact mapping and confirmed by successful ablation. The distribution of the target sites in the three-dimensional reconstructed geometry of the RVOT was classified in three directions: (i) anterior (A)/posterior (P); (ii) free wall (F)/septal (Se); and (iii) superior (Su)/inferior (I). The ECG characteristics were then analysed according to the three-dimensional distribution of the target sites. 3. The following indices were helpful to identify the position of the target site: (i) QRS duration (> or = 150 msec = F; < 150 msec = Se; P < 0.05); (ii) the R wave pattern in the inferior leads (RR' or Rr' = F; R = Se; P < 0.05); (iii) the R wave amplitude in the inferior leads (high = Se; low = F; P < 0.05); (iv) the initial r wave width in lead V(1) (wide = F; narrow = Se; P < 0.05); (v) the QS wave amplitude in aVR and aVL (if aVR < aVL, A; if aVR > or = aVL, P; P < 0.05); and (vi) the initial r wave amplitude in lead V(1) and V(2) (if V(1) > or = 0.15 mV and V(2) > or = 0.3 mV, Su; if V(1) < 0.15 mV or V(2) < 0.3 mV, I; P < 0.05). 4. In conclusion, the ECG characteristics were associated with target site locations in all three directions.

Growth differentiation factor-15 combined with N-terminal prohormone of brain natriuretic peptide increase 1-year prognosis prediction value for patients with acute heart failure: a prospective cohort study.

BACKGROUND: Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers. The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15 (GDF-15) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in assessing hospitalized patients with acute heart failure (AHF). METHODS: In total, 260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016. Medical history and blood samples were collected within 24 h after the admission. The primary endpoint was the all-cause mortality within 1 year. The patients were divided into survival group and death group based on the endpoint. With established mortality risk factors and serum GDF-15 level, receiver-operator characteristic (ROC) analyses were performed. Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15. RESULTS: Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors (P < 0.001). In ROC analyses, area under curve (AUC) for GDF-15 to predict 1-year mortality was 0.707 (95% confidence interval [CI]: 0.648-0.762, P < 0.001), and for NT-proBNP was 0.682 (95% CI: 0.622-0.738, P < 0.001). No statistically significant difference was found between the two markers (P = 0.650). Based on the optimal cut-offs (GDF-15: 4526.0 ng/L; NT-proBNP: 1978.0 ng/L), the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction (AUC = 0.743, 95% CI: 0.685-0.795, P < 0.001). CONCLUSIONS: GDF-15, as a prognostic marker in patients with AHF, is not inferior to NT-proBNP. Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis. CLINICAL TRIAL REGISTRATION: ChiCTR-ONC-12001944, http://www.chictr.org.cn.

Negative regulation of quinone reductase 2 by resveratrol in cultured vascular smooth muscle cells.

1. Resveratrol, a polyphenol in red wine, has a cardioprotective effect. Resveratrol-targeting protein (RTP) has been purified using a resveratrol affinity column (RAC) and has been identified as quinone reductase type 2 (NQO2). We hypothesize that NQO2 is the target protein of resveratrol in vascular smooth muscle cells (VSMC) and that resveratrol inhibits proliferation of VSMC through its action on NQO2. In the present study, we investigated the correlation between NQO2 regulation and cell proliferation in VSMC in response to resveratrol treatment. 2. The RTP was purified using RAC and was detected with a NQO2 polyclonal antibody. The VSMC were incubated with resveratrol (1, 10 and 50 micromol/L) for 24, 48 and 72 h. Cell proliferation was detected by cell counting and bromodeoxyuridine (BrdU) assay. A lentiviral vector incorporating NQO2 short interference (si) RNA of short hairpin design was constructed and transduced into VSMC. Real-time quantitative polymerase chain reaction was used to measure NQO2 mRNA levels; NQO2 expression was determined by western blot analysis. 3. Using RAC, we extracted a 26 kDa protein from aortic smooth muscle, which was referred to as RTP-26. Proliferation of VSMC was inhibited by resveratrol in a concentration- and time-dependent manner. The mRNA and protein expression of NQO2 was also repressed by resveratrol in a concentration- and time-dependent manner. A similar pattern of inhibition was observed for cells treated with resveratrol (25 micromol/L) as for cells transduced with a lentiviral vector containing siRNA sequences against NQO2. 4. Collectively, these data indicate that the suppression of VSMC proliferation mediated by resveratrol correlates with NQO2 downregulation.

[Detection of gene mutations of SCN5A in 7 patients with Brugada syndrome].

OBJECTIVE: Brugada syndrome is linked to sodium channel mutations and could induce arrhythmias that even lead to sudden death. The purpose of this study was to detect if there was gene mutation of SCN5A in 7 patients with Brugada syndrome and explore the molecular genetic characteristics of this disease. METHOD: Genomic DNA was extracted from peripheral blood of all 7 patients with Brugada syndrome and 41 pairs of PCR primers were designed to amplify all the 28 exons of SCN5A. RESULT: There was no novel mutation in exons of Gene SCN5A in these patients with Brugada syndrome. CONCLUSION: Brugada syndrome might associated gene mutation or other mechanisms independent of SCN5A gene mutation.

Brachial-ankle pulse wave velocity compared with mean arterial pressure and pulse pressure in risk stratification in a Chinese population.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) can be easily measured in an observer-independent way, but lacks robust population-based validation in terms of fatal combined with nonfatal outcomes. METHOD: To address this issue, we studied 4251 Chinese randomly recruited Gaoyou County (54.1% women; mean age, 52.1). RESULTS: In the whole study population, mean values were 102.4 mmHg for mean arterial pressure (MAP), 51.1 mmHg for pulse pressure, and 14.8 m/s for baPWV. Over 4.4 years (median), 74 participants experienced a fatal or nonfatal cardiovascular event and 44 a stroke. In multivariable-adjusted Cox regression, standardized hazard ratios expressing the risk of a composite cardiovascular endpoint were 1.77 (95% confidence interval, 1.43-2.20), 1.37 (1.14-1.64) and 1.50 (1.26-1.78) for MAP, PP and baPWV, respectively; the corresponding hazard ratios for stroke were 1.82 (1.39-2.38), 1.39 (1.12-1.74) and 1.53 (1.25-1.89). baPWV did not add to the prediction of cardiovascular events or stroke by MAP (hazard ratios for baPWV, 1.25 and 1.27, respectively; P ≥ 0.053) but refined models including PP (hazard ratios, 1.42 and 1.45; P ≤ 0.0033). The optimized baPWV threshold, obtained by maximizing Youden's index (16.7 m/s), increased the integrated discrimination improvement over and beyond MAP (+1.27%; P = 0.021) and PP (+1.37%; P = 0.038) for the cardiovascular outcome, but not stroke, and increased the net reclassification improvement for both endpoints (≥42.2%; P ≤ 0.004). CONCLUSION: With fatal and nonfatal cardiovascular and cerebrovascular endpoints as outcome, baPWV marginally increases risk stratification over and beyond MAP, but is a better predictor than PP. A threshold of 16.7 m/s might be used in Chinese populations.

[Electrophysiological findings and ablation strategies in patients with atrial tachyarrhythmias after left atrial circumferential ablation in the treatment of atrial fibrillation].

OBJECTIVE: To report the electrophysiological findings and the ablation strategies in patients with atrial tachyarrhythmias (ATAs) or atrial fibrillation (AF) recurrence after left atrial circumferential ablation (LACA) in the treatment of AF. METHODS: 91 patients with AF had LACA procedure from April 2004 to May 2006, 19 of which accepted the second ablation procedure due to ATAs or AF recurrence. In all the 19 patients [17 male, 2 female, age 25 - 65 (53 +/- 12) years], 11 presented with paroxysmal AF before the first ablation procedure, 2 with persistent AF and 6 with permanent AF. Pulmonary vein potentials (PVP) were investigated in both sides in all the patients. RESULTS: Delayed PVP was identified inside the left circular line in 5 patients, in the right in 1 and both in 2 during sinus rhythm. "Gap" conduction was found and successfully closed guided by circular mapping catheter. In 3 cases, irregular left atrial tachycardia was caused by fibrillation rhythm inside the left ring via decremental "gap" conduction. Reisolation was done successfully again guided by 3-D mapping and made the left atrium in sinus rhythm but the fibrillation rhythm was still inside the left ring. Pulmonary vein tachycardia with 1:1 conduction to the left atrium presented in one case and reisolation stopped the tachycardia. No PVP was discovered in both sides in 4 patients but other tachycardias could be induced, including two right atrial scar related tachycardias, two supraventricular tachycardias mediated by concealed accessory pathway, one cavo-tricuspid isthmus dependent atrial flutter and one focal atrial tachycardia near the coronary sinus ostium. All the tachycardias in these 4 patients were successfully ablated with the help of routine and 3-D mapping techniques. In the rest 3, which were in AF rhythm, LACA was successfully done again. After a mean follow-up of 4 - 26 (11.5 +/- 8.5) months, 16 patients were symptom free without anti-arrhythmic drug therapy; 1 of them had frequent palpitation attack with Holter recording of atrial premature contractions; 2 of them with permanent AF became paroxysmal in one, and still in AF in the other. CONCLUSIONS: Reconduction between the left atrium and the pulmonary veins is the dominant factor for post-LACA ATAs and AF recurrence. Other forms of atrial tachycardias or supraventricular tachycardias may coexist with AF or sometimes trigger AF. LACA can not sufficiently modify AF substrate in some permanent AF patients.

[Tpeak-Tend interval and risk of cardiac events in patients with Brugada syndrome].

OBJECTIVE: To evaluate the possible association between Tpeak-Tend (Tp-e) interval in surface standard ECG and cardiac events in patients with Brugada syndrome (BrS). METHOD: Tp-e interval in surface standard ECG was compared between BrS patients (n = 23, all males) and paroxysmal supraventricular tachycardia (PSVT) patients (n = 20, all males) as well as between BrS patients with (n = 16) or without (n = 7) cardiac events. RESULTS: There was significant difference in Tp-e interval between BrS patients and PSVT patients [(109.57 +/- 22.86) ms vs. (88.50 +/- 13.08) ms, P < 0.05]. Tp-e interval was also significantly longer in BrS patients with cardiac events (syncope, clinical ventricular fibrillation and induced VF during electrophysiological study) than BrS patients without cardiac events [(118.12 +/- 20.40) ms vs. (90.00 +/- 15.27) ms, P < 0.05] while Tp-e interval was similar between BrS patients without cardiac events and PSVT patients (P > 0.05). CONCLUSION: The prolongation of Tp-e (> or = 120 ms) was associated with higher cardiac events in BrS patients.

[Time distribution of ventricular arrhythmias in patients with Brugada syndrome].

OBJECTIVE: To study the characterization of time distribution of ventricular arrhythmias in patients with Brugada syndrome (BrS) using Holter monitoring and ICD follow-up. METHODS: Patients with BrS [all male, mean age (41.07 +/- 11.49) years], were divided into ventricular fibrillation (VF) group (n = 7) and no ventricular fibrillation (N-VF) group (n = 7). Premature ventricular capture (PVC) and VF episodes were detected by Holter monitoring and ICD recording. RESULTS: The 24 hours total number of PVCs ranged from 0 to 74 (mean 9.61 +/- 17.23) in most of the patients and were similar between VF group and N-VF group. The percentage of PVC episodes in VF group was significantly higher than that in N-VF group from nocturnal time to early morning (22:00 to 7:00, 98.67% vs. 44.14%, P < 0.01). There were total 75 VF episodes during (23.18 +/- 17.96) months' follow-up in 5 patients with BrS, 93.3% of which occurred from nocturnal time to early morning (22:00 to 7:00). CONCLUSIONS: The episodes of PVC were enriched from nocturnal time to early morning in BrS patients, this time distribution could be a new noninvasive risk stratification factor for BrS. The episodes of VF in BrS patients were also enriched from nocturnal time to early morning and this time characteristic of episodes of VF could be used to guide drug therapy.

[Left atrium linear lesion encircling pulmonary veins guided by EnSite-NavX and double-Lasso technique for paroxysmal atrial fibrillation].

OBJECTIVE: To evaluate the efficacy of left atrium linear lesion encircling pulmonary veins (PV) guided by EnSite-NavX and double-Lasso technique for paroxysmal atrial fibrillation (PAF). METHODS: Twenty-two patients (male 19, mean age of 48.5 years +/- 11.4 years) with symptomatic PAF were enrolled. After a geometry of the left atrium was reconstructed by EnSite-NavX system, PV ostia were marked on the map based on venography. Two Lasso catheters were placed within the ipsilateral superior and inferior PVs. Irrigated radiofrequency energy was applied at 0.5-1.0 cm of distance from the PV ostia. Continuous linear lesion was done to obtain the disappearance of pulmonary vein potentials. Patients were on propafenone and perindopril for three months after the procedure. RESULTS: The endpoint for ablation was reached in 21 Patients and 1 patient was not successful because of cardiac tamponade. The mean procedure time was 6.6 h +/- 1.3 h and the mean X-ray exposure time was 56.1 min +/- 18.0 min. After a mean 5.3 months +/- 2.7 months of follow-up, 10 patients were free of symptoms. Two patients had no PAF recurrence after the second procedure. Three patients had clinical recurrence of PAF in the first month. The total success rate in this study was 81% (17/21). Mortality was 0% and the overall complication rate was about 9% (2/22). CONCLUSION: Left atrium circumferential linear ablation surrounding PV ostia guided by EnSite-NavX and double-Lasso technique is effective in PAF, but some patients will need more than one procedure in order to achieve a success.

[The electrophysiological study and implantable cardioverter defibrillator therapy for the patients with Brugada syndrome].

OBJECTIVE: Clinical observation of electrophysiological study and implantable cardioverter defibrillator (ICD) therapy in patients with Brugada syndrome. METHODS: Ten patients (all male) with Brugada wave (spontaneous or propafenone test positive in ECG) underwent electrophysiological study (EPS). The mean age was (41 +/- 10) years. They had no structural heart disease with echocardiogram and the angiogram work-up. The ICD implanted in the patients with EPS-induced ventricular fibrillation in those who were available. RESULTS: Three patients had the history of familial sudden cardiac death (SCD). Four patients had repeated syncope episodes, two of them had documented ventricular fibrillation during syncope episodes. The AH and HV intervals were 50 - 124 (86 +/- 21) ms and 41 - 84 (58 +/- 15) ms. The ventricular fibrillation was induced in four patients with syncope and atrioventricular reentry tachycardia in one patient with palpitation. Three patients had spontaneous or inducible atrial fibrillation. The ICD implanted in three patients with inducible ventricular fibrillation. Due to economic issue, one patient without ICD implantation had got SCD during follow-up. The patient with atrioventricular reentry tachycardia underwent a successful left atrioventricular accessory pathway ablation. CONCLUSION: The Brugada patients with syncope and high rate of inducible ventricular fibrillation in EPS are the high risk population for SCD, in whom ICD should implant promptly to prevent SCD.

Rapid component I(Kr) of cardiac delayed rectifier potassium currents in guinea-pig is inhibited by alpha(1)-adrenoreceptor activation via protein kinase A and protein kinase C-dependent pathways.

Ventricular tachyarrhythmias are often precipitated by physical or emotional stress, indicating a link between increased adrenergic stimulation and cardiac ion channel activity. Human ether-a-go-go related gene (hERG) potassium channels conduct the rapid component of delayed rectifier potassium current, I(kr), a crucial component for action potential repolarization. To evaluate the correlation between increased alpha(1)-adrenergic activity and the rapid component of cardiac I(kr), whole-cell patch-clamp recording was performed in isolated guinea-pig ventricular myocytes. Stimulation of alpha(1)-adrenoceptors using phenylephrine (0.1 nM-100 microM) reduced I(kr) current in a dose-dependent manner at 37 degrees C. Phenylephrine (0.1 microM) reduced I(kr) current to 66.83+/-3.16%. Chelerythrine (1 microM), a specific inhibitor of protein kinase C (PKC) completely inhibited the changes in I(kr) trigged by 0.1 microM phenylephrine. KT5720 (2.5 microM), a specific inhibitor of protein kinase A (PKA) partially inhibited the current decrease induced by 0.1 microM phenylephrine. Both chelerythrine and KT5720 drastically reduced the phenylephrine-induced effects, indicating possible involvement of PKC and PKA in the alpha(1)-adrenergic inhibition of I(kr). Our data suggest a link between I(kr) and the alpha(1)-adrenoceptor, involving activation of PKC and PKA in arrhythmogenesis.

Swimming training can affect intrinsic calcium current characteristics in rat myocardium.

Endurance exercise is widely assumed to improve cardiac function in humans, but the mechanisms involved in such changes are not clearly understood. The purpose of this study is to determine whether training elicits adaptations at the level of the L-type Ca(2+) channel. Sprague-Dawley rats performed swimming training at either moderate intensity (MOD) or high intensity (HIGH) during 8 weeks. The trained rats were studied by echocardiography and the whole-cell L-type Ca(2+) currents (I (Ca,L)) characteristics in a single cell were measured by standard whole-cell patch-clamp recording technique. Echocardiography showed that septal and posterior wall thickness in MOD and HIGH increased with the increased LV mass by 43 and 41%, respectively (P < 0.05). Training (P < 0.05) increased mean myocyte capacitance (approximately 38% in MOD and HIGH) and myocyte length (approximately 20% longer in MOD and 26% longer in HIGH), thus providing electrophysiological and morphological evidence that the training elicited LV cardiocyte hypertrophy. Mean peak I (Ca,L) was not different in three groups. However, whole-cell I (Ca,L) density was decreased in MOD and HIGH versus sedentary (P < 0.05), but there was no significant difference between MOD and HIGH. The present study provides the evidence of a training adaptation in intrinsic I (Ca,L) characteristics in ventricular myocardium, which demonstrates a remarkable adaptive plasticity of L-type channel characteristics in training rat heart.

Hypoxia reoxygenation induces premature senescence in neonatal SD rat cardiomyocytes.

AIM: To investigate whether hypoxia reoxygenation induces premature senescence in neonatal Sprague-Dawley (SD) rat cardiomyocytes. METHODS: Cardiomyocytes were isolated from neonatal SD rat heart and identified by immunohistochemistry. The control cultures were incubated at 37 degree centigrade in a humidified atmosphere of 5% CO(2) and 95% air. The hypoxic cultures were incubated in a modular incubator chamber filled with 1% O(2), 5% CO(2), and balance N2 for 6 h. The reoxygenated cultures were subjected to 1% O(2) and 5% CO(2) for 6 h, then 21% oxygen for 4, 8, 12, 24, and 48 h, respectively. Cell proliferation was determined using bromodeoxyuridine labeling. The ultrastructure of cardiomyocytes was observed by using an electron microscope. beta-Galactosidase activity was determined by using a senescence beta-galactosidase Staining Kit. p16( INK4a ) and telomerase reverse transcriptase (TERT) mRNA levels were measured by real time quantitative PCR. TERT protein expression was determined by immunohistochemistry. Telomerase activities were assayed by using the Telo TAGGG Telomerase PCR ELISAplus kit. RESULTS: The initial cultures consisted of pure cardiomyocytes identified by immunohistochemistry. The proportion of BrdU positive cells was reduced significantly in the hypoxia reoxygenation-treated group (P< 0.01). Under the condition of hypoxia reoxygenation, mitochondrial dehydration appeared; p16( INK4a ) and TERT mRNA levels, beta-galactosidase activity, TERT protein expression and telomerase activities were all significantly increased (P< 0.01 or P< 0.05). CONCLUSION: These data indicate that premature senescence could be induced in neonatal SD rat cardiomyocytes exposed to hypoxia reoxygenation. Although TERT significantly increased, it could not block senescence.