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Aim: The objective of this study was to examine the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) on coronary arterial large conductance Ca2+ -activated K+ (BK) channel function in coronary smooth muscle cells (SMCs) of streptozotocin- induced diabetic rats. Methods: The effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on coronary BK channel open probabilities were determined using the patch clamp technique. The mRNA and protein expressions of BK channel subunits were measured using qRTPCR and Western blots. The coronary artery tension and coronary SMC Ca2+ concentrations were measured using a myograph system and fluorescence Ca2+ indicator. Results: Compared to nondiabetic control rats, the BK channel function was impaired with a reduced response to EPA and DHA in freshly isolated SMCs of diabetic rats. Oral administration of n-3 PUFAs had no effects on protein expressions of BK channel subunits in nondiabetic rats, but significantly enhanced those of BK-β 1 in diabetic rats without altering BK-a protein levels. Moreover, coronary ring tension induced by iberiotoxin (a specific BK channel blocker) was increased and cytosolic Ca2+ concentrations in coronary SMCs were decreased in diabetic rats, but no changes were found in nondiabetic rats. Conclusions: n-3 PUFAs protect the coronary BK channel function and coronary vasoreactivity in diabetic rats as a result of not only increasing BK-β 1 protein expressions, but also decreasing coronary artery tension and coronary smooth muscle cytosolic Ca2+ concentrations. [ABSTRACT FROM AUTHOR]

Aims: Fragmented QRS (f-QRS) complexes are associated with adverse cardiovascular events in patients with coronary heart disease; however, the effects on patients with dilated cardiomyopathy (DCM) remain elusive. This study is to investigate the changes of left ventricular (LV) synchrony and systolic function in DCM patients with f-QRS complexes.Methods and Results: Twenty DCM patients with f-QRS complexes and 29 DCM patients without f-QRS (n-QRS) complexes were enrolled. The LV segmental longitudinal, radial and circumferential time to peak strain and general longitudinal systolic strain, radial strain, circumferential strain were measured, respectively, by speckle tracking imaging. The LV segmental standard deviations and maximal differences were also calculated. The LV dyssynchrony was defined as the time in peak anteroseptal wall to posterior wall strain >130 ms or longitudinal strain delay index >25%. The mean QRS durations in f-QRS and n-QRS groups were not different (P = ns). The incidence of LV dyssynchrony was 15/20 (75%) vs. 5/29 (17%) in two groups (P < 0.01). Two patients died of sudden death in f-QRS group during 2 years follow-up; however, no death in n-QRS group (P < 0.05). Patients in f-QRS group showed worsening LV dyssynchrony in f-QRS group after 2 years follow-up (P < 0.05). Overall, LV function was comparable at baseline (P = ns), but had significantly worsened only in the f-QRS group (P < 0.05).Conclusion: The f-QRS complex is significantly associated with LV dyssynchrony in DCM patients and can be used as a reliable index to evaluate ventricular synchrony and predict the prognosis in DCM patients with narrow QRS complexes. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) not only is an independent risk factor for death but also confers significant risk of morbidity from stroke associated with left atrial thrombus. The association of interleukin 6 (IL-6) polymorphism with thrombus in AF has not been investigated before. We carried out a case–control study in Han Chinese. The IL-6 −634C/G genotypes of 31 patients with thrombus and 45 patients without thrombus were detected by polymerase chain reaction and restriction fragment length polymorphism. The frequencies of the IL-6 genotypes (CC, CG, and GG) were 29.03%, 54.54%, and 16.13% for the patients with thrombus, and 55.56%, 40.00%, and 4.44% for the patients without thrombus, respectively (P = .0391). Compared with the CC genotype, the G allele carriers (CG + GG) had a 2.79-fold increased risk of thrombus or severe spontaneous echocontrast (SEC). These results suggest that IL-6 −634C/G polymorphism is associated with thrombus and severe SEC, and the G allele is an independent risk for thrombus and severe SEC in Han Chinese patients with AF. [ABSTRACT FROM PUBLISHER]

Background: Administration of androgens decreases plasma concentrations of high-density lipid cholesterol (HDL-C). However, the mechanisms by which androgens mediate lipid metabolism remain unknown. This present study used HepG2 cell cultures and ovariectomized C57BL/6 J mice to determine whether apolipoprotein M (ApoM), a constituent of HDL, was affected by dihydrotestosterone (DHT). Methods: HepG2 cells were cultured in the presence of either DHT, agonist of protein kinase C (PKC), phorbol-12-myristate-13-acetate (PMA), blocker of androgen receptor flutamide together with different concentrations of DHT, or DHT together with staurosporine at different concentrations for 24 hrs. Ovariectomized C57BL/6 J mice were treated with DHT or vehicle for 7d or 14d and the levels of plasma ApoM and livers ApoM mRNA were measured. The mRNA levels of ApoM, ApoAI were determined by real-time RT-PCR. ApoM and ApoAI were determined by western blotting analysis. Results: Addition of DHT to cell culture medium selectively down-regulated ApoM mRNA expression and ApoM secretion in a dose-dependent manner. At 10 nM DHT, the ApoM mRNA levels were about 20% lower than in untreated cells and about 40% lower at 1000 nM DHT than in the control cells. The secretion of ApoM into the medium was reduced to a similar extent. The inhibitory effect of DHT on ApoM secretion was not blocked by the classical androgen receptor blocker flutamide but by an antagonist of PKC, Staurosporine. Agonist of PKC, PMA, also reduced ApoM. At 0.5 μM PMA, the ApoM mRNA levels and the secretion of ApoM into the medium were about 30% lower than in the control cells. The mRNA expression levels and secretion of another HDL-associated apolipoprotein AI (ApoAI) were not affected by DHT. The levels of plasma ApoM and liver ApoM mRNA of DHT-treated C57BL/6 J mice were lower than those of vehicle-treated mice. Conclusions: DHT directly and selectively down-regulated the level of ApoM mRNA and the secretion of ApoM by protein kinase C but independently of the classical androgen receptor. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dysfunction is linked to myocardial ischemia-reperfusion (I/R) injury. Checkpoint kinase 1 (CHK1) could facilitate cardiomyocyte proliferation, however, its role on mitochondrial function in I/R injury remains unknown., Methods: To investigate the role of CHK1 on mitochondrial function following I/R injury, cardiomyocyte-specific knockout/overexpression mouse models were generated. Adult mouse cardiomyocytes (AMCMs) were isolated for in vitro study. Mass spectrometry-proteomics analysis and protein co-immunoprecipitation assays were conducted to dissect the molecular mechanism., Results: CHK1 was downregulated in myocardium post I/R and AMCMs post oxygen-glucose deprivation/re‑oxygenation (OGD/R). In vivo, CHK1 overexpression protected against I/R induced cardiac dysfunction, while heterogenous CHK1 knockout exacerbated cardiomyopathy. In vitro, CHK1 inhibited OGD/R-induced cardiomyocyte apoptosis and bolstered cardiomyocyte survival. Mechanistically, CHK1 attenuated oxidative stress and preserved mitochondrial metabolism in cardiomyocytes under I/R. Moreover, disrupted mitochondrial homeostasis in I/R myocardium was restored by CHK1 through the promotion of mitochondrial biogenesis and mitophagy. Through mass spectrometry analysis following co-immunoprecipitation, SIRT1 was identified as a direct target of CHK1. The 266-390 domain of CHK1 interacted with the 160-583 domain of SIRT1. Importantly, CHK1 phosphorylated SIRT1 at Thr530 residue, thereby inhibiting SMURF2-mediated degradation of SIRT1. The role of CHK1 in maintaining mitochondrial dynamics control and myocardial protection is abolished by SIRT1 inhibition, while inactivated mutation of SIRT1 Thr530 fails to reverse the impaired mitochondrial dynamics following CHK1 knockdown. CHK1 Δ390 amino acids (aa) mutant functioned similarly to full-length CHK1 in scavenging ROS and maintaining mitochondrial dynamics. Consistently, cardiac-specific SIRT1 knockdown attenuated the protective role of CHK1 in I/R injury., Conclusions: Our findings revealed that CHK1 mitigates I/R injury and restores mitochondrial dynamics in cardiomyocytes through a SIRT1-dependent mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Heart failure is a prevalent and life-threatening syndrome characterized by structural and/or functional abnormalities of the heart. As a global burden with high rates of morbidity and mortality, there is growing recognition of the beneficial effects of exercise on physical fitness and cardiovascular health. A substantial body of evidence supports the notion that exercise can play a protective role in the development and progression of heart failure and improve cardiac function through various mechanisms, such as attenuating cardiac fibrosis, reducing inflammation, and regulating mitochondrial metabolism. Further investigation into the role and underlying mechanisms of exercise in heart failure may uncover novel therapeutic targets for the prevention and treatment of heart failure., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Ventricular arrhythmias are the leading cause of sudden cardiac death in patients after myocardial infarction (MI). Connexin43 (Cx43) is the most important gap junction channel-forming protein in cardiomyocytes. Dysfunction of Cx43 contributes to impaired myocardial conduction and the development of ventricular arrhythmias. Following an MI, Cx43 undergoes structural remodeling, including expression abnormalities, and redistribution. These alterations detrimentally affect intercellular communication and electrical conduction within the myocardium, thereby increasing the susceptibility to post-infarction ventricular arrhythmias. Emerging evidence suggests that post-translational modifications play essential roles in Cx43 regulation after MI. Therefore, Cx43-targeted management has the potential to be a promising protective strategy for the prevention and treatment of post infarction ventricular arrhythmias. In this article, we primarily reviewed the regulatory mechanisms of Cx43 mediated post-translational modifications on post-infarction ventricular arrhythmias. Furthermore, Cx43-targeted therapy have also been discussed, providing insights into an innovative treatment strategy for ventricular arrhythmias after MI., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The aim of this study was to investigate the effects and mechanisms of SGLT2 inhibitor empagliflozin on diabetic coronary function., Methods: A rat diabetic model was established by injection of streptozotocin. Rats in the treated group were administered empagliflozin by gavage and rat coronary vascular tensions were measured after eight weeks. Large conductance calcium activated K + channel currents were recorded using a patch clamp technique, while human coronary artery smooth muscle cells were used to explore the underlying mechanisms., Results: After incubation with empagliflozin (10, 30, 100, 300, 1000 μmol/L), the Δ relaxation % of rat coronary arteries were 2.459 ± 1.304, 3.251 ± 1.119, 6.946 ± 3.407, 28.36 ± 11.47, 86.90 ± 3.868, respectively. Without and with empagliflozin in the bath solution, BK channel opening probabilities at a membrane potential of +60 mV were 0.0458 ± 0.0517 and 0.3413 ± 0.2047, respectively ( p < 0.05, n = 4 cells). After incubation with iberiotoxin, the Δ tensions of rat coronary arteries in the control (Ctrl), untreated (DM), low empagliflozin (10 mg/kg/d)-treated (DM+L-EMPA) and high empagliflozin (30mg/kg/d)-treated (DM+H-EMPA) group were 103.20 ± 5.85, 40.37 ± 22.12, 99.47 ± 28.51, 78.06 ± 40.98, respectively ( p < 0.01 vs Ctrl, n = 3-7; p < 0.001 vs DM+L-EMPA, n = 5-7). Empagliflozin restored high glucose-induced downregulation of Sirt1, Nrf2, and BK-β1, while the effect of empagliflozin disappeared in the presence of EX-527, a Sirt1 selective inhibitor., Conclusion: Empagliflozin has a vasodilation effect on the coronary arteries in a concentration-dependent manner and can activate BK channels via the Sirt1-Nrf2 mechanism., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Kong et al.)

Background: Recent evidence revealed that glucose fluctuation might be more likely to cause arrhythmia than persistent hyperglycemia, whereas its mechanisms were elusive. We aimed to investigate the effect of glucose fluctuation on the occurrence of ventricular arrhythmia and its mechanism., Methods: Streptozotocin (STZ) induced diabetic rats were randomized to five groups: the controlled blood glucose (C-STZ) group, uncontrolled blood glucose (U-STZ) group, fluctuated blood glucose (GF-STZ) group, and GF-STZ rats with 100 mg/kg Tempol (GF-STZ + Tempol) group or with 5 mg/kg KN93 (GF-STZ + KN93) group. Six weeks later, the susceptibility of ventricular arrhythmias and the electrophysiological dysfunctions of ventricular myocytes were evaluated using electrocardiogram and patch-clamp technique, respectively. The levels of reactive oxygen species (ROS) and oxidized CaMKII (ox-CaMKII) were determined by fluorescence assay and Western blot, respectively. Neonatal rat cardiomyocytes and H9C2 cells in vitro were used to explore the underlying mechanisms., Results: The induction rate of ventricular arrhythmias was 10%, 55%, and 90% in C-STZ group, U-STZ group, and GF-STZ group, respectively (P < 0.05). The electrophysiological dysfunctions of ventricular myocytes, including action potential duration at repolarization of 90% (APD 90 ), APD 90 short-term variability (APD 90 -STV), late sodium current (I Na-L ), early after depolarization (EAD) and delayed after depolarizations (DAD), as well as the levels of ROS and ox-CaMKII, were significantly increased in GF-STZ group. In vivo and ex vivo, inhibition of ROS or ox-CaMKII reversed these effects. Inhibition of I Na-L also significantly alleviated the electrophysiological dysfunctions. In vitro, inhibition of ROS increase could significantly decrease the ox-CaMKII activation induced by glucose fluctuations., Conclusions: Glucose fluctuations aggravated the I Na-L induced ventricular arrhythmias though the activation of ROS/CaMKII pathway., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Glucose fluctuations (GF) are a risk factor for cardiovascular complications associated with type 2 diabetes. However, there is a lack of adequate research on the effect of GF on myocardial fibrosis and the underlying mechanisms in type 2 diabetes. This study aimed to investigate the impact of glucose fluctuations on myocardial fibrosis and explore the potential mechanisms in type 2 diabetes., Methods: Sprague Dawley (SD) rats were randomly divided into three groups: the control (Con) group, the type 2 diabetic (DM) group and the glucose fluctuations (GF) group. The type 2 diabetic rat model was established using a high-fat diet combined with low-dose streptozotocin injection and the GF model was induced by using staggered glucose and insulin injections daily. After eight weeks, echocardiography was used to assess the cardiac function of the three groups. Hematoxylin-eosin and Masson staining were utilized to evaluate the degree of pathological damage and fibrosis. Meanwhile, a neonatal rat cardiac fibroblast model with GF was established. Western and immunofluorescence were used to find the specific mechanism of myocardial fibrosis caused by GF., Results: Compared with rats in the Con and the DM group, cardiac function in the GF group showed significant impairments. Additionally, the results showed that GF aggravated myocardial fibrosis in vitro and in vivo. Moreover, Ca 2+ /calmodulin‑dependent protein kinase II (CaMKII) was activated by phosphorylation, prompting an increase in phosphorylation of signal transducer and activator of transcription 3 (Stat3) and induced nuclear translocation. Pretreatment with KN-93 (a CaMKII inhibitor) blocked GF-induced Stat3 activation and significantly suppressed myocardial fibrosis., Conclusions: Glucose fluctuations exacerbate myocardial fibrosis by triggering the CaMKII/Stat3 pathway in type 2 diabetes., (© 2023. The Author(s).)

Background: Diabetes is associated with myocardial fibrosis, while the underlying mechanisms remain elusive. The aim of this study is to investigate the underlying role of calcineurin/nuclear factor of activated T cell 3 (CaN/NFATc3) pathway and the Enhancer of zeste homolog 2 (EZH2) in diabetes-related myocardial fibrosis., Methods: Streptozotocin (STZ)-injected diabetic rats were randomized to two groups: the controlled glucose (Con) group and the diabetes mellitus (DM) group. Eight weeks later, transthoracic echocardiography was used for cardiac function evaluation, and myocardial fibrosis was visualized by Masson trichrome staining. The primary neonatal rat cardiac fibroblasts were cultured with high-glucose medium with or without cyclosporine A or GSK126. The expression of proteins involved in the pathway was examined by western blotting. The nuclear translocation of target proteins was assessed by immunofluorescence., Results: The results indicated that high glucose treatment increased the expression of CaN, NFATc3, EZH2 and trimethylates lysine 27 on histone 3 (H3K27me3) in vitro and in vivo. The inhibition of the CaN/NFATc3 pathway alleviated myocardial fibrosis. Notably, inhibition of CaN can inhibit the nuclear translocation of NFATc3, and the expression of EZH2 and H3K27me3 protein induced by high glucose. Moreover, treatment with GSK126 also ameliorated myocardial fibrosis., Conclusion: Diabetes can possibly promote myocardial fibrosis by activating of CaN/NFATc3/EZH2 pathway., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Dilated cardiomyopathy (DCM) is characterized by the left ventricular dilatation and impaired myocardial systolic dysfunction with high mortality and morbidity. However, the underlying mechanisms remain elusive. We first identified the differentially expressed genes (DEGs) between the DCM and control group using two expression profiles from GSE3585 and GSE84796. Enrichment analysis was conducted to explore the potential mechanisms underlying DCM. A total of four algorithms, including key module of MCODE, degree, maximum neighborhood component (MNC), and maximal clique centrality (MCC), were used to identify the hub genes within Cytoscape. The correlation between hub genes and infiltrated immune cells was evaluated to determine potential immune-related genes. The expression analysis and diagnosis value analysis of potential immune-related genes were performed. Finally, the expression analysis with GSE57338 and relationship analysis with the comparative toxicogenomics database (CTD) were performed to identify the key immune-related genes in DCM. A total of 80 DEGs were screened for DCM. Enrichment analysis revealed that DEGs were involved in the immune-related pathological process. Immune infiltration analysis indicated a potentially abnormal immune response in DCM. Four up-regulated genes (COL1A2, COL3A1, CD53, and POSTN) were identified as potential immune-related genes. Finally, three genes (COL1A2, COL3A1, and POSTN) were determined as the key immune-related genes in DCM via expression analysis with a validation set (GSE57338) and relationship analysis with CTD. Our study suggested that the upregulated COL1A2, COL3A1, and POSTN might be the key immune-related genes for DCM. Further studies are needed to validate the underlying mechanisms., (© 2023. The Author(s).)

Objective: We aimed to screen out biomarkers for atrial fibrillation (AF) based on machine learning methods and evaluate the degree of immune infiltration in AF patients in detail., Methods: Two datasets (GSE41177 and GSE79768) related to AF were downloaded from Gene expression omnibus (GEO) database and merged for further analysis. Differentially expressed genes (DEGs) were screened out using "limma" package in R software. Candidate biomarkers for AF were identified using machine learning methods of the LASSO regression algorithm and SVM-RFE algorithm. Receiver operating characteristic (ROC) curve was employed to assess the diagnostic effectiveness of biomarkers, which was further validated in another independent validation dataset of GSE14975. Moreover, we used CIBERSORT to study the proportion of infiltrating immune cells in each sample, and the Spearman method was used to explore the correlation between biomarkers and immune cells., Results: 129 DEGs were identified, and CYBB, CXCR2, and S100A4 were identified as key biomarkers of AF using LASSO regression and SVM-RFE algorithm. Both in the training dataset and the validation dataset, CYBB, CXCR2, and S100A4 showed favorable diagnostic effectiveness. Immune infiltration analysis indicated that, compared with sinus rhythm (SR), the atrial samples of patients with AF contained a higher T cells gamma delta, neutrophils and mast cells resting, whereas T cells follicular helper were relatively lower. Correlation analysis demonstrated that CYBB, CXCR2, and S100A4 were significantly correlated with the infiltrating immune cells., Conclusions: In conclusion, this study suggested that CYBB, CXCR2, and S100A4 are key biomarkers of AF correlated with infiltrating immune cells, and infiltrating immune cells play pivotal roles in AF., (© 2022. The Author(s).)

The Sorbin and SH3 domain-containing protein 2 (Sorbs2) is an important component of cardiomyocyte sarcomere. It has been recently reported that loss of Sorbs2 is causally associated with arrhythmogenic cardiomyopathy in human. However, the ionic mechanisms leading to cardiac arrhythmogenesis by Sorbs2 deficiency are unknown. In this study, we hypothesized that Sorbs2 plays an important role in regulating cardiac ion channel expression and function. Using electrophysiological and molecular biological approaches, we found that the Sorbs2 knockout (KO) mice progressively developed cardiac structural and electrical remodeling as early as 1 to 2 months of age and died prematurely at 5 to 7 months of age. Electrocardiographic recordings showed that Sorbs2 KO mice had conduction delays, spontaneous ventricular extrasystoles and polymorphic ventricular tachyarrhythmia. Intracellular recordings revealed abnormal action potentials with depolarized resting potential, reduced upstroke velocity, prolonged repolarization, and effective refractory period in the ventricular preparations of Sorbs2 KO mice. Patch clamp experiments demonstrated that Sorbs2 KO mice displayed distinct abnormalities in the expression and function of cardiac ion channels, including those of the voltage-gated Na + channels, L-type Ca 2+ channels, the voltage-gated K + channels and the inward-rectifier K + channels. Moreover, Sorbs2 physically interacted with the RNAs and/or proteins of important cardiac ion channels and directly regulated their expression in vitro. Our results indicate that Sorbs2 plays a pivotal role in the regulation of cardiac channel physiology. Loss of Sorbs2 promotes cardiac ion channelopathies and life-threatening arrhythmias., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Co-expression network may contribute to better understanding molecular interaction patterns underlying cellular processes. To explore microRNAs (miRNAs) expression patterns correlated with AF, we performed weighted gene co-expression network analysis (WGCNA) based on the dataset GSE28954. Thereafter, we predicted target genes using experimentally verified databases (ENOCRI, miRTarBase, and Tarbase), and overlapped genes with differentially expressed genes (DEGs) from GSE79768 were identified as key genes. Integrated analysis of association between hub miRNAs and key genes was conducted to screen hub genes. In general, we identified 3 differentially expressed miRNAs (DEMs) and 320 DEGs, predominantly enriched in inflammation-related functional items. Two significant modules (red and blue) and hub miRNAs (hsa-miR-146b-5p and hsa-miR-378a-5p), which highly correlated with AF-related phenotype, were detected by WGCNA. By overlapping the DEGs and predicted target genes, 38 genes were screened out. Finally, 9 genes (i.e. ATP13A3, BMP2, CXCL1, GABPA, LIF, MAP3K8, NPY1R, S100A12, SLC16A2) located at the core region in the miRNA-gene interaction network were identified as hub genes. In conclusion, our study identified 2 hub miRNAs and 9 hub genes, which may improve the understanding of molecular mechanisms and help to reveal potential therapeutic targets against AF., (© 2021. The Author(s).)

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the world. Although much technological progress in the treatment of AF has been made, there is an urgent need for better treatment of AF due to its high rates of morbidity and mortality. The anti-arrhythmic drugs currently approved for marketing have significant limitations and side effects such as life-threatening ventricular arrhythmias and hypotension. The small conductance Ca 2+ -activated K + channels (SK channels) are dependent on intracellular Ca 2+ concentrations, which tightly integrate with membrane potential. Given the predominant expression in the atria of many species, including humans, they are now emerging as a therapeutic target for treating AF. This review aimed to illustrate the characteristics and function of SK channels. Moreover, it discussed the regulation of SK channels and their potential as a therapeutic target of AF., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Glucose fluctuations may contribute to large conductance calcium activated potassium (BK) channel dysfunction. However, the underlying mechanisms remain elusive. The aim of this study was to investigate the molecular mechanisms involved in BK channel dysfunction as a result of glucose fluctuations. A rat diabetic model was established through the injection of streptozotocin. Glucose fluctuations in diabetic rats were induced via consumption and starvation. Rat coronary arteries were isolated and coronary vascular tensions were measured after three weeks. Rat coronary artery smooth muscle cells were isolated and whole-cell BK channel currents were recorded using a patch clamp technique. Human coronary artery smooth muscle cells in vitro were used to explore the underlying mechanisms. After incubation with iberiotoxin (IBTX), the Δ tensions (% Max) of rat coronary arteries in the controlled diabetes mellitus (C-DM), the uncontrolled DM (U-DM) and the DM with glucose fluctuation (GF-DM) groups were found to be 84.46 ± 5.75, 61.89 ± 10.20 and 14.77 ± 5.90, respectively (P < .05), while the current densities of the BK channels in the three groups were 43.09 ± 4.35 pA/pF, 34.23 ± 6.07 pA/pF and 17.87 ± 4.33 pA/pF, respectively (P < .05). The Δ tensions (% Max) of rat coronary arteries after applying IBTX in the GF-DM rats injected with 0.9% sodium chloride (NaCl) (GF-DM + NaCl) and the GF-DM rats injected with N-acetyl-L-cysteine (NAC) (GF-DM + NAC) groups were found to be 8.86 ± 1.09 and 48.90 ± 10.85, respectively (P < .05). Excessive oxidative stress and the activation of protein kinase C (PKC) α and nuclear factor (NF)-κB induced by glucose fluctuations promoted the decrease of BK-β1 expression, while the inhibition of reactive oxygen species (ROS), PKCα, NF-κB and muscle ring finger protein 1 (MuRF1) reversed this effect. Glucose fluctuations aggravate BK channel dysfunction via the ROS overproduction and the PKCα/NF-κB/MuRF1 signaling pathway., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Fragmented QRS (f-QRS) complexes are associated with adverse cardiovascular events in patients with coronary heart disease; however, the effects on patients with dilated cardiomyopathy (DCM) remain elusive. This study is to investigate the changes of left ventricular (LV) synchrony and systolic function in DCM patients with f-QRS complexes., Methods and Results: Twenty DCM patients with f-QRS complexes and 29 DCM patients without f-QRS (n-QRS) complexes were enrolled. The LV segmental longitudinal, radial and circumferential time to peak strain and general longitudinal systolic strain, radial strain, circumferential strain were measured, respectively, by speckle tracking imaging. The LV segmental standard deviations and maximal differences were also calculated. The LV dyssynchrony was defined as the time in peak anteroseptal wall to posterior wall strain >130 ms or longitudinal strain delay index >25%. The mean QRS durations in f-QRS and n-QRS groups were not different (P = ns). The incidence of LV dyssynchrony was 15/20 (75%) vs. 5/29 (17%) in two groups (P < 0.01). Two patients died of sudden death in f-QRS group during 2 years follow-up; however, no death in n-QRS group (P < 0.05). Patients in f-QRS group showed worsening LV dyssynchrony in f-QRS group after 2 years follow-up (P < 0.05). Overall, LV function was comparable at baseline (P = ns), but had significantly worsened only in the f-QRS group (P < 0.05)., Conclusion: The f-QRS complex is significantly associated with LV dyssynchrony in DCM patients and can be used as a reliable index to evaluate ventricular synchrony and predict the prognosis in DCM patients with narrow QRS complexes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Objective: To investigate the effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) diastolic function measured by speckle tracking imaging (STI) in patients with dilated cardiomyopathy (DCM)., Methods: CRT was performed in 21 DCM patients [15 male, mean age: 61.2 ± 11.2 (49-82) years].LV synchronization, LV systolic function and LV diastolic function were evaluated with conventional echocardiography, tissue Doppler imaging and STI before and 6 months after CRT.NYHA heart function was also assessed. Clinic Response to CRT was defined as improvement of more than 1 NYHA class.Response to CRT in echocardiography was defined as ≥ 15% reduction in LV end systolic volume at 6 months post CRT., Results: There were 16 responders and 5 non-responders at 6 months post CRT.In terms of diastolic function, conventional echocardiography derived deceleration time was both prolonged in non-responders and responders. At 6 months post CRT, STI derived LV isovolumetric diastolic strain rate [(0.19 ± 0.11) /s vs.(0.14 ± 0.09)/s, P < 0.001] was significantly increased while early diastolic mitral valve blood flow velocity/left ventricular isovolumetric diastolic strain rate (680 ± 600 vs.787 ± 690, P < 0.04) was significantly reduced in responder group while remained unchanged in non-responder group.Furthermore, left ventricular isovolumetric diastolic strain rate negatively correlated with plasma brain natriuretic peptide level (r = -0.68, P < 0.05)., Conclusion: In CRT responders of DCM patients, LV diastolic function is significantly improved and this change could be detected more effectively by STI derived LV diastolic function parameters.

Objective: To assess the association between 1019C/T polymorphism of Connexin 37 (CX37) gene and susceptibility to restenosis after percutaneous coronary intervention (PCI) in ethnic Han Chinese patients from Wuxi., Methods: Five hundred and thirty-two patients with coronary artery disease (CAD) who had undergone PCI underwent coronary angiography (CAG) in 3 months, and were divided into in stent restenosis (ISR) group (n=67) and no instent restenosis (NISR) group (n=465). Five hundred and one healthy individuals have served as the control group. All cases were genotyped with DNA sequencing., Results: Compared with healthy controls, the frequency of CX37 C allele was higher in CAD patients (57.05% vs. 41.32%, P< 0.01). The frequency of C carries (CC+TC) was 79.32% in CAD patients, against 65.47% in healthy controls (P<0.01). The risk for CAD was significantly increased in carriers of C allele (CC+TC) compared with TT homozygotes (OR=2.03, 95% CI: 1.53-2.80). Stratified analysis has indicated a significant difference in the frequency of C allele carriers between both male and female CAD patients and healthy controls (79.63% vs. 72.45%, P=0.02; 78.00% vs. 51.50%, P< 0.01). For both genders, carriers of C allele had a higher risk for CAD compared with TT homozygotes (males: OR=1.48, 95% CI: 1.06-2.09; females: OR=3.34, 95% CI: 1.90-5.86). Compared with NISR group, the frequency of CX37 C allele and C carries (CC+TC) were significantly higher in ISR group (72.39% vs. 54.84%, P< 0.01; 89.55% vs. 77.85%, P=0.027). Compared with TT homozygotes, the risk for restenosis has significantly increased in carriers of C allele (CC+TC) (OR=2.44, 95% CI: 1.08-5.50). Stratified analysis also suggested that the frequency of C carriers was significantly higher in male ISR group compared with male NISR group (92. 86% vs. 77.66%, P=0.008). The risk for restenosis has increased by nearly four fold in carriers of C allele (CC+TC) compared with TT homozygotes (95% CI: 1.32-10.64). However, for female patients, no significant difference was detected in the ISR risk between carriers of CC+TC type and TT homozygotes (P=0.655)., Conclusion: The C allele of 1019C/T polymorphism in the CX37 gene is associated with susceptibility to CAD as well as restenosis after coronary stenting in male patients from Wuxi.

Studies have shown that a C1019T polymorphism of the gene encoding the gap junction protein connexin37 is associated with coronary artery disease (CAD). The aim of the present study was to explore the association between the C1019T polymorphism in the connexin37 gene and CAD patients with in-stent restenosis (ISR). A total of 532 patients who had undergone coronary stenting and coronary angiography at least three months after the procedure were divided according to a clinical diagnosis standard into two groups which were ISR (n=67) and no in-stent restenosis (NISR; n=465) groups. A further 501 healthy individuals were controls. The subjects were genotyped by DNA sequencing. The results demonstrated the following: i) connexin37 gene 1019 sites in the population were distributed by polymorphism into three genetic types (CC, TC and TT types). The distribution frequency of the healthy control, ISR and NISR groups conformed to the Hardy-Weinberg genetic balance rule; ii) in comparison with the healthy controls, the frequency of the connexin37 C allele was higher in the CAD patients (57.05% vs. 41.32%; OR, 1.89; 95% CI, 1.58-2.25; P<0.01). The frequency of the C carriers (CC+TC) was 65.47% in the healthy controls, vs. 79.32% in CAD patients (P<0.01). The CAD risk was significantly increased in the carriers of the C allele (CC+TC) compared with TT homozygotes (OR, 2.03; 95% CI, 1.53-2.80; P<0.01). Stratified analysis demonstrated that a significant difference existed in the frequency of C carriers between the male CAD patients and healthy controls (79.63% vs. 72.45%; OR, 1.48; 95% CI, 1.06-2.09, P=0.02), as well as in the female CAD patients (78.00% vs. 51.50%; OR, 3.34; 95% CI, 1.90-5.86; P<0.01). In the female and male CAD patients, the frequency of the connexin37 C allele was higher than in the healthy controls (male: χ(2)=12.67, P<0.01; female: χ(2)=50.20, P<0.01); iii) compared with the NISR group, the frequencies of the connexin37 C allele and C carriers (CC+TC) were significantly higher in the ISR group (frequency of C allele: 72.39% vs. 54.84%; P<0.01; frequency of C carriers: 89.55% vs. 77.85%; P=0.03). Compared with TT homozygotes, the restenosis risk was significantly increased in the carriers of the C allele (CC+TC; OR, 2.44; 95% CI, 1.08-5.50). Subsequent stratified analysis revealed that the frequency of the C allele was significantly higher in the male ISR group than in the male NISR group (78.57% vs. 52.66%; OR, 3.30; 95% CI, 2.05-5.29; P<0.01). The restenosis risk was ∼four-fold higher in the C carriers (CC+TC) than in the TT homozygotes (OR, 3.74; 95% CI, 1.32-10.64). However in the female population, there was no difference in the ISR risk between the carriers of the C allele (CC+TC) and the TT homozygotes (P=0.70). In summary, the C allele of the connexin37 gene is not only is associated with the susceptibility to CAD, but also associated with restenosis following coronary stenting in the population studied herein, particularly the male population.

Objective: To investigate the changes of open probability (Po) of large conductance Ca(2+)-activated K(+) channel (BK channel) in diabetic coronary smooth muscle cells and elucidate the underlying cellular electrophysiology mechanisms of coronary dysfunction., Methods: Rat coronary smooth muscle cells were isolated from control group and diabetic group. BK single channel currents were recorded by patch clamp technique in inside-out configuration. Open probabilities were calculated and compared between two groups. After exposure to DHS-1, a specific BK channel activator, Po at 0.2 and 1 µmol/L free Ca(2+) were compared between control and diabetic groups., Results: In the presence of 0.2 µmol/L free Ca(2+), the Po at baseline was significantly lower in diabetic rats than in control rats (0.0032 ± 0.0012 vs. 0.095 ± 0.036, P < 0.05). Cytoplasmic application of DSH-1 significantly increased the Po to 0.335 ± 0.096 (P < 0.05 vs. baseline) in control rats, whereas DSH-1 had no effect in diabetic rats (Po = 0.022 ± 0.018, P > 0.05 vs. baseline). In the presence of 1 µmol/L free Ca(2+), the Po at baseline was also significantly lower in diabetic rats than in control rats (0.210 ± 0.055 vs. 0.458 ± 0.077, P < 0.05). Cytoplasmic application of DHS-1 further robustly enhanced Po to 0.823 ± 0.019 (P < 0.05 vs. baseline) in control rats and to 0.446 ± 0.098 in diabetic rats (P < 0.05 vs. baseline of diabetic rats; P < 0.05 vs. control rats with DHS-1)., Conclusion: The decrease of Po of BK single channel in coronary smooth muscle cells may be a potential cause for coronary dysfunction in diabetic rats.

Objective: To observe the prognostic value of admission B-type natriuretic peptide (BNP) on outcome for patients with congestive heart failure (CHF)., Methods: Blood BNP levels, routine echocardiography and tissue Doppler image were obtained in 162 CHF patients [95 male, mean age: (71.8±3.7) years] at admission. Patients were divided into high BNP (BNP>1500 ng/L, n=104) and low BNP (BNP≤1500 ng/L, n=58) groups. All patients were followed up for 2 years and clinical characteristics, echocardiography including Doppler image and cardiovascular events results were analyzed. Data were also compared between patients with (n=48) or without (n=107) cardiovascular events., Results: Left ventricular ejection fractions (LVEF) was significantly lower [(40.9±5.6)% vs. (44.0±5.9)%, P<0.01] while the total cardiovascular events rate (49.1% vs. 21.0%, P<0.01) and cardiac mortality rate (25.5% vs. 9.0%, P<0.01) were significantly higher in high BNP group than in low BNP group. BNP level at admission in event group was significantly higher than in event-free group [(2875.4±325.7) ng/L vs. (1136.9±298.6) ng/L, P<0.000]. BNP level was positively related to Tei-index (r=0.793, P<0.001) and negatively correlated with LVEF (r=-0.57, P<0.001). Multiple logistic regression analysis demonstrated that BNP, LVEF, Tei-index and β-blocker use were independent risk factors for cardiovascular events. The area under the ROC curve for predicting cardiovascular death within 2 years in event group by BNP was 0.795 (95%CI 0.693-0.935, sensitivity: 72.31% and specificity: 84.62%, cut-off BNP value: 1910 ng/L). The event risk was 2.17 times higher in CHF patients with admission BNP>1910 ng/L compared CHF patients with admission BNP≤1910 ng/L (95%CI: 1.852-2.954, P=0.000)., Conclusion: Admission BNP level, LVEF, Tei-index and β-blocker use are independent risk factors for cardiovascular events in patients with CHF. Patients with higher admission BNP level (>1910 ng/L) is linked with worse prognosis in this patient cohort.

Objective: To evaluate left ventricular (LV) function and twist in patients with diabetic cardiovascular autonomic neuropathy (CAN) by two-dimensional speckle tracking imaging (STI)., Methods: STI was performed in 56 subjects with type 2 diabetes mellitus (DM) (35 with DM only: group A, 21 with CAN: group B) and 34 normal subjects (Control) from LV short-axis view. LV peak systolic, peak early (E') and peak late (A') diastolic circumferential strain in 18 myocardial segments were measured at the levels of mitral annulus, papillary muscle and apex and the rotation at mitral annulus and apex levels were also measured. LV peak systolic and the ratio of E' and A' of global and three levels, twist, untwisting rate and untwisting half-time were calculated., Results: In group A, compared with control group, LV peak systolic radial circumferential strain has no significant difference (P > 0.05), E'/A' was reduced (P < 0.05), twist at aortic valve closure and twist at mitral valve opening were significantly increased (P < 0.05), untwisting rate reduced, and untwisting half time delayed. In group B, compared with control group and group A, circumferential strain parameters [(-12.64 ± 6.49)% vs. (-19.11 ± 9.98)% and (-21.14 ± 10.13)%, P < 0.05] and E'/A' [(0.90 ± 0.35) vs. (1.24 ± 0.47) and (1.98 ± 0.63), P < 0.05] were significantly decreased, twist at aortic valve closure [(19.08 ± 5.62)° vs. (16.57 ± 2.84)° and (14.36 ± 4.06)°, P < 0.05] and twist at mitral valve opening [(13.99 ± 2.31)° vs. (11.36 ± 2.63)° and (9.04 ± 5.63)°, P < 0.05] were significantly increased, untwisting rate [(0.40 ± 0.28)%/ms vs. (0.46 ± 0.14)%/ms and (0.53 ± 0.21)%/ms, P < 0.05] reduced, and untwisting half time [(489.61 ± 97.14) ms vs. (445.21 ± 54.53) ms and (410.60 ± 50.23) ms, P < 0.05] delayed., Conclusion: Speckle tracking imaging could be used to evaluate early changes on LV twist deformation and LV systolic function in patients with type 2 diabetes mellitus.

Objective: To investigate the effects of docosahexaenoic acid (DHA) on sodium channel current (I(Na)) and transient outward potassium channel current (I(to)) in rat ventricular myocytes and to evaluate potential anti-arrhythmic mechanisms of DHA., Methods: I(Na) and I(to) of individual ventricular myocytes were recorded by patch-clamp technique in whole-cell configuration at room temperature. Effects of DHA at various concentrations (0, 20, 40, 60, 80, 100 and 120 micromol/L) on I(Na) and I(to) were observed., Results: (1) I(Na) was blocked in a concentration-dependent manner by DHA, stably inactivated curves were shifted to the left, and recover time from inactivation was prolonged while stably activated curves were not affected by DHA. At -30 mV, I(Na) was blocked to (1.51 ± 1.32)%, (21.13 ± 4.62)%, (51.61 ± 5.73)%, (67.62 ± 6.52)%, (73.49 ± 7.59)% and (79.95 ± 7.62)% in the presence of above DHA concentrations (all P < 0.05, n = 20), and half-effect concentration (EC(50)) of DHA on I(Na) was (47.91 ± 1.57)micromol/L. (2) I(to) were also blocked in a concentration-dependent manner by DHA, stably inactivated curves were shifted to the left, and recover time from inactivation was prolonged with increasing concentrations of DHA, and stably activated curves were not affected by DHA. At +70 mV, I(to) was blocked to (2.61 ± 0.26)%, (21.79 ± 4.85)%, (63.11 ± 6.57)%, (75.52 ± 7.26)%, (81.82 ± 7.63)% and (84.33 ± 8.25)%, respectively, in the presence of above DHA concentrations (all P < 0.05, n = 20), and the EC(50) of DHA on I(to) was (49.11 ± 2.68)micromol/L., Conclusion: The blocking effects of DHA on APD and I(to) may serve as one of the anti-arrhythmia mechanisms of DHA.

Objective: To investigate the mechanism of enhanced large conductance calcium-activated potassium channel currents (BK) in coronary smooth muscle cells (SMCs) by docosahexaenoic acid (DHA)., Methods: Coronary SMCs were isolated by enzyme digestion. Potassium channels in coronary SMCs were identified by applications of different potassium blockers. Effects of DHA and its metabolite 16, 17-epoxydocosapentaenoic acid (16, 17-EDP) on BK channels in the absence and presence of cytochrome P450 epoxygenase inhibitor SKF525A were studied by patch clamp in whole-cell configuration., Results: BK channels were widely distributed in SMCs, and BK currents in normal SMCs accounted for (64.2 ± 2.7)% of total potassium currents (n = 20). DHA could activate BK channels, and its 50% effective concentration (EC(50)) was (0.23 ± 0.03) µmol/L, however, the effect of DHA on BK channels was abolished after SMCs were incubated with cytochrome P450 epoxygenase inhibitor SKF525A. 16, 17-EDP, a metabolite of DHA, could reproduce the effects of DHA on BK channels, and its EC(50) was (19.7 ± 2.8) nmol/L., Conclusion: DHA and metabolites can activate BK channels and dilate coronary arteries through activating cytochrome P450 epoxygenase pathway.

Objective: To observe serum C4a and platelet aggregation rates changes in acute myocardial infarction (AMI) patients before and after percutaneous coronary intervention (PCI) and association with the development of no-reflow phenomenon., Methods: From June 2006 to August 2009, 119 AMI patients underwent PCI (28 cases of no-reflow group, 91 cases of reflow group) and 30 subjects with suspected coronary heart diseases and normal coronary angiography results (control group) were enrolled in this study. C4a and platelet aggregation rate were measured at 30 minutes before PCI, immediately after PCI, 30 minutes, 1 hour, 2 hour, and 6 months post PCI in AMI patients and at before coronary angiography in control subjects., Results: The levels of serum C4a at 30 minutes prior to PCI in control, no-reflow, and reflow groups were similar (P > 0.05). Platelet aggregation rate at 30 minutes prior to PCI was significantly higher in no-reflow group and reflow group than in control group (all P < 0.05). Serum C4a and platelet aggregation rates were significantly higher in no-reflow group at immediate, 30 minutes and 1 hour after PCI than at 30 minutes prior to PCI, two hours and 6 months after PCI (all P < 0.05), and were significantly higher than in reflow group at immediate, 30 minutes and 1 hour after PCI (all P < 0.05). Serum C4a and platelet aggregation rates were similar at different time points in reflow group (all P > 0.05). The levels of C4a in no-reflow group at immediate, 30 minutes and 1 hour after PCI were positively correlated with platelet aggregation rates (r = 0.91, 0.79, 0.60, respectively, all P < 0.01)., Conclusion: The transient increase on levels of C4a and platelet aggregation rate early post PCI are verified in no-reflow patients with AMI undergoing PCI.

Objective: To investigate the changes of large conductance Ca(2+)-activated K(+) channel (BK channel) on coronary smooth muscle cells from diabetic rats., Methods: Streptozotocin-induced rat diabetic animal model was used. Coronary smooth muscle cells were isolated by enzyme digestion. BK currents in control and diabetic groups were recorded by patch clamp technique in whole cell configuration, and BK channel protein expression was detected by Western blot. Calcium concentration was measured by fluorescence assay., Results: Compared with control group, BK current densities in diabetic group were significantly decreased when test potentials > 100 mV (P < 0.05). BK current densities were (275 ± 40) pA/pF in control group (n = 8) and (70 ± 10) pA/pF in diabetic group (n = 6) at 150 mV test potentials. α-subunit protein expression was similar between the groups (P > 0.05), however, β1-subunit protein expression was significantly reduced in diabetic group than in control group (P < 0.05). Calcium concentrations were significantly increased in diabetic group control group (151 ± 18) nmol/L (n = 6) than in control group (92 ± 7) nmol/L (n = 5, P < 0.05)., Conclusion: Observed β1-subunit downregulation, BK current density decrease and cytosolic calcium concentration increase in smooth muscle cells of diabetic coronary arteries may be associated with coronary dysfunction in diabetic rats.

Objective: To investigate the clinical features of severe chronic heart failure patients with normal B-type natriuretic peptide (BNP)., Methods: A total of 57 patients with severe chronic heart failure (New York Heart Association class III and IV) were included in this prospective control study from Dec. 2002 to Oct. 2009. Group A included 13 patients with normal BNP (< 100 ng/L) and group B included 44 patients with increased BNP (> 100 ng/L). Group A patients were followup for (19.6 ± 14.7) months and group B patients for (72.5 ± 17.1) months., Results: The baseline clinical characteristics of two groups were comparable. Left ventricular end diastolic diameter (LVEDd) of group A was larger than group B [(70.56 ± 4.33) mm vs.(63.73 ± 3.75) mm, P < 0.05], the left ventricular ejection fraction (LVEF) of group A was lower than group B [(24.16 ± 2.50)% vs. (28.49 ± 2.63)%, P < 0.05]. The number of patents tolerating metoprolol in group A is lower than in group B (7/13 vs. 39/44, P < 0.05), and the tolerant dose of metoprolol in group A is lower than in group B [(12.5 ± 6.25) mg/d vs. (24.20 ± 11.22) mg/d, P < 0.05]. The level of BNP in group B were significantly higher at acute stages than at remission stages [(962.73 ± 165.00) ng/L vs. (876.24 ± 167.70) ng/L, P < 0.05], but remained unchanged in group A [(74.03 ± 11.18) ng/L vs. (71.38 ± 11.68) ng/L, P > 0.05]. The mortality of group A was higher than group B (11/12 vs. 6/44, P < 0.05). The binary logistic regression analysis (backward) showed that normal B-type natriuretic peptide was an independent predictor of cardiovascular mortality in patients with severe chronic heart failure (OR = 45.488, 95%CI = 5.322 - 388.791)., Conclusion: Normal BNP in patients with severe chronic heart failure suggests the exhaustion of BNP secretion and associated poor prognosis.

Objective: to investigate the regulation in vascular tension of diabetic coronary artery by large conductance Ca(2+)-activated K(+) channel (BK channel) and to elucidate the mechanisms of coronary dysfunctions due to diabetes., Methods: regulation of vascular tension in normal coronary artery was evaluated by videomicroscopy system. Streptozotocin-induced rat diabetic animal model was established successfully by intraperitoneal injection. Coronary smooth muscle cells were isolated by enzyme digestion. The BK currents in control and diabetic groups were recorded by patch clamp technique in whole cell configuration. Changes of vascular tension in normal and diabetic coronary arteries were assayed by multi-wire myograph system., Results: more than 50% was contracted in inner diameters of coronary arteries when 100 nmol/L IBTX, a specific BK channel blocker, was applied. In comparison with normal group, the BK current densities in diabetic group significantly decreased when test potentials were more than 60 mV (P < 0.05). The BK current densities at 150 mV in normal group and diabetic group were (275 ± 40) pA/pF and (70 ± 10) pA/pF respectively. When 100 mmol/L KCl was washed out, vascular tensions of normal and diabetic coronary artery were (398 ± 38) mg and (390 ± 35) mg respectively (P > 0.05); however, when 100 nmol/L IBTX was added, the vascular tensions of normal and diabetic coronary artery were (395 ± 40) mg and (50 ± 7) mg (P < 0.05)., Conclusion: BK channels play an important role in the regulation of coronary vascular tension, whereas BK channels in diabetic coronary artery are dysfunction, BK currents decrease and vascular tensions increase.

Objective: To determine the feasibility on the left ventricular systolic synchronism and cardiac function evaluation in patients with permanent cardiac pacing by real-time three-dimensional echocardiography., Methods: Fifteen patients with sick sinus syndrome post dual-chamber pacemaker implantation were enrolled in this study. Pacemakers were programmed to AAI, DDD, and VVI respectively. After pacing for 5 minutes in each mode, participants were examined with real-time three-dimensional echocardiography. Images in different pacing modes were obtained and analyzed by the off-line Qlab 4.2 software. Parameters including global and 17-segmental volume-time curves (VTCs), dispersion of time to minimal regional volume for 16, 12, and 6 left ventricular segments (Tmsv16-s, Tmsv12-s, Tmsv6-s), and maximal difference of time to minimal regional volume for l6, 12 and 6 left ventricular segments (Tmsv16-dif, Tmsv12-dif, Tmsv6-dif), end diastolic volume (EDV), end systolic volume (ESV), left ventricular ejection fraction (LVEF) were measured respectively. Parameters of peak filling rate (PFR), regional end diastolic volume (rEDV), regional end systolic volume (rESV), and regional ejection fraction (rEF) were also calculated., Results: Left ventricular systolic synchronism as reflected by VTCs, Tmsv16-s, Tmsv12-s, Tmsv6-s, Tmsv16-dif, Tmsv12-dif and Tmsv6-dif as well as parameters reflecting ventricular function, i.e., LVEF, PFR were significantly better in AAI mode than in DDD and VVI models (all P < 0.05). All above indexes were similar between DDD and VVI models (all P > 0.05). rEFs of left inferior wall in base, septum in base and apex were significantly lower in DDD and VVI models compared that in AAI mode (P < 0.05)., Conclusion: Real-time three-dimensional echocardiography can objectively and accurately evaluate left ventricular systolic synchronism and cardiac function in patients with permanent cardiac pacing and AAI mode is superior to DDD and VVI models.

Objective: To investigate the effects of docosahexaenoic acid (DHA) on action potential (AP) and transient outward potassium current (I(to)) on ventricular myocytes of Sprague-Dawley rat., Methods: Calcium-tolerant ventricular myocytes were isolated by enzyme digestion. The changes of AP and I(to) with increasing DHA at concentrations of 0, 10, 20, 40, 60, 80, 100, 120 and 200 micromol/L were recorded by whole-cell patch clamp configuration., Results: (1) Action potential durations (APDs) were not affected by DHA at concentrations from 0 micromol/L to 30 micromol/L, while APDs were gradually prolonged in proportion with increasing DHA concentrations from 30 micromol/L to 200 micromol/L within 5 minutes and remained stable thereafter. APD(25), APD(50) and APD(75) were (7.7 +/- 2.0) ms, (21.2 +/- 3.5) ms, and (100.1 +/- 9.8) ms respectively at 100 micromol/L DHA. APD(25), APD(50), and APD(75) were (15.2 +/- 4.0) ms, (45.7 +/- 6.8) ms, and (215.6 +/- 15.7) ms respectively at 200 micromol/L DHA. (2) I(to) was gradually reduced with the increasing DHA concentrations from 10 micromol/L to 200 micromol/L. I(to) was blocked by DHA in a dose-dependent manner. I(to) current density was (30.1 +/- 7.2) pA/pF at DHA concentration of 60 micromol/L and its half-inhibition concentration was 58.3 micromol/L., Conclusion: APDs are gradually prolonged while I(to) reduced with increasing concentrations of DHA which might contribute to the anti-arrhythmia mechanisms of DHA.

Objective: Amlodipine (Aml) has R- and S-isomers with different pharmacological effects. However, no data are available on the influence of (S)-Aml and (R)-Aml on L-type calcium channel current (I(Ca-L)) or cytosolic calcium (Ca2+). This study is to investigate effects on I(Ca-L) and cytosolic Ca2+., Methods: I(Ca-L), peak currents, I-V curves, steady state activation curves, steady state inactivation curves and recovery curves from inactivation with (S)-Aml and (R)-Aml were recorded by whole-cell patch clamp configuration. Cytosolic Ca2+ of smooth muscle cells was assayed by Fura-2/AM., Results: At the concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, 1.5 +/- 0.2%, 25.4 +/- 5.3%, 65.2 +/- 7.3%, 78.4 +/- 8.1%, and 94.2 +/- 5.0% of I(Ca-L) were blocked by (S)-Aml. I-V curves were shifted upward. Half-activation voltages were -16.01 +/- 1.65 mV, -17.61 +/- 1.60 mV, -20.17 +/- 1.46 mV, -21.87 +/- 1.69 mV and -24.09 +/- 1.87 mV (P < 0.05). Half-inactivation voltages were -27.16 +/- 4.48 mV, -28.69 +/- 4.52 mV, -31.19 +/- 4.17 mV, -32.63 +/- 4.34 mV and -35.16 +/- 4.46 mV (P < 0.05). Recovery time were prolonged gradually (P < 0.05). 10.3 +/- 1.2%, 35.2 +/- 3.5%, 60.1 +/- 5.0%, 78.9 +/- 6.1%, and 91.2 +/- 7.6% of cytosolic Ca2+ were reduced at different concentrations (P < 0.05). However, (R)-Aml at different concentrations had no effect on I(Ca-L) and cytosolic Ca2+ (P > 0.05)., Conclusion: Only (S)-Aml has calcium channel blockade activity, while (R)-Aml has none of the pharmacologic actions associated with CCBs.