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BACKGROUND In the development of coronary stent technology, bioresorbable scaffolds are promising milestones in improving the clinical treatment of coronary artery disease. The “leave nothing behind” motto is the premise of the fourth revolution in percutaneous coronary intervention (PCI). Studies proving the safety and efficacy of the magnesium-based resorbable scaffolds (MgBRSs) include the BIOSOLVE-I and BIOSOLVE-II trials and the latest BIOSOLVE-IV registry. However, spontaneous retrograde dissection of a partially absorbed MgBRS may still occur, albeit rarely. CASE SUMMARY We describe an unusual case of coronary artery disease in a patient who had undergone a successful PCI 8 mo earlier, where an MgBRS was implanted into the left anterior descending artery (LAD) and left circumflex artery with drug-coated balloons for a ramus intermedius branch stenosis to achieve the “leave nothing behind” therapeutic intention and was currently presenting with a gradual worsening of chest tightness. The distal edge vascular response, during subsequent attempts with balloon angioplasty was performed smoothly. However, spontaneous retrograde dissection of a partially absorbed MgBRS in the LAD ensued. Successful bailout stenting was performed with revascularization of the entry and exit sites created by spontaneous dissection and complete sealing of the intramural hematoma. The patient recovered well and was discharged after 2 d of intervention. When followed up in August 2020 (7 mo later), the patient showed uneventful recovery. CONCLUSION Spontaneous retrograde dissection of a partially absorbed MgBRS was successfully treated using bailout sirolimus-eluting coronary stent strategy.

Background Brugada syndrome is a disorder associated with sudden cardiac death and characterized by an abnormal electrocardiogram (ECG). Previous studies were predominantly conducted in men, and the data on long-term prognosis are limited. Information about women, especially elderly women, is lacking. Objective The aim of this study was to investigate the long-term prognosis of the Brugada ECG pattern in elderly women. Method We investigated the 10-year prognosis of the Brugada ECG pattern in elderly women in a nationwide community-based population in Taiwan. Community-dwelling women older than 55 years were prospectively recruited from December 2008 to March 2013 by a stratified random sampling method. All enrolled individuals were followed up annually until April 2019, and the cause of death was documented by citizen death records. Results Among 2597 women, 60 (2.31%) had a Brugada-type ECG, and this prevalence was higher than the mean global prevalence of 0.23%. One woman had a type 1 ECG (0.04%), whereas 15 (0.58%) and 44 (1.70%) women had type 2 and type 3 ECG patterns, respectively. Cox survival analysis revealed that all-cause mortality and cardiac mortality were similar in the individuals with and without a Brugada-type ECG during a mean follow-up of 96.1 ± 20.5 months. Conclusions Our findings suggest that Brugada ECG patterns are not infrequent in elderly women but are not associated with increased risk of mortality in long-term follow-up; these findings may help reduce unnecessary anxiety for physicians, nurses, allied health caregivers, and patients.

MURC (muscle‐restricted coiled‐coil protein) is a hypertrophy‐related gene. Hypertrophy can be induced by mechanical stress. The purpose of this research was to investigate the hypothesis that MURC mediates hypertrophy in cardiomyocytes under mechanical stress. We used the in vivo model of an aortocaval shunt (AV shunt) in adult Wistar rats to induce myocardial hypertrophy. We also used the in vitro model of cyclic stretch in rat neonatal cardiomyocytes to clarify MURC expression and the molecular regulation mechanism. The flexible membrane culture plate seeding with cardiomyocytes Cardiomyocytes seeded on a flexible membrane culture plate were stretched by vacuum pressure to 20% of maximum elongation at 60 cycles/min. AV shunt induction enhanced MURC protein expression in the left ventricular myocardium. Treatment with atorvastatin inhibited the hypertrophy induced by the AV shunt. Cyclic stretch markedly enhanced MURC protein and mRNA expression in cardiomyocytes. Addition of extracellular‐signal‐regulated kinase (ERK) inhibitor PD98059, ERK small interfering RNA (siRNA), angiotensin II (Ang II) antibody and atorvastatin before stretch, abolished the induction of MURC protein. An electrophoretic mobility shift assay showed that stretch enhanced the DNA binding activity of serum response factor. Stretch increased but MURC mutant plasmid, ERK siRNA, Ang II antibody and atorvastatin reversed the transcriptional activity of MURC induced by stretch. Adding Ang II to the cardiomyocytes also induced MURC protein expression. MURC siRNA and atorvastatin inhibited the hypertrophic marker and protein synthesis induced by stretch. Treatment with atorvastatin reversed MURC expression and hypertrophy under volume overload and cyclic stretch.

The name Fon-Jou Hsieh was inadvertently omitted from the list of authors. The name should be added as the third author of the article.

Complete right bundle branch block (CRBBB) occurs in 0.2% to 1.3% of the general population, but its prognostic significance in the geriatric population is unknown. We prospectively investigated the prevalence and prognostic value of CRBBB in individuals aged ≥65 years in a community-based population in Taiwan. A total of 5,830 community-dwelling individuals were prospectively recruited from 7 regions across Taiwan starting in December 2008 through March 2013. Those aged ≥65 years were included in the analysis (N=3,383). All subjects underwent a home visit and standardized medical exams and were followed up annually until the end of April 2019; cause of death was documented by citizen death records. The mean age of the study cohort was 73.5±5.9 years (65-104), and 47.21% were men. Among these individuals, 171 (5.05%) had CRBBB; the prevalence was higher in men (7.08%) than in women (3.25%). Subjects with CRBBB were older than those without CRBBB (75.4±6.5 vs. 73.4±5.9), and the frequency of CRBBB increased with age. Survival analysis revealed that all-cause mortality and cardiac mortality were similar in individuals with and without CRBBB during a mean follow-up of 92.6±23.6 months. CRBBB is not associated with increased risk of mortality in the geriatric population.

AIM CHA2 DS2 -VASc score has been proven to have great prognostic value in patients with acute coronary syndrome (ACS). We aimed to determine whether the addition of renal dysfunction in the CHA2 DS2 -VASc score would improve the prognostic impact of the scoring system to predict prognosis among ACS patients. METHODS A total of 3031 ACS patients were prospectively enrolled at 39 hospitals and followed for 1 year. The patients were divided into three groups based on estimated glomerular filtration rate (eGFR) (group 1, eGFR>90; group 2, eGFR between 60 and 90; and group 3, eGFR

Background: Diabetes mellitus (DM) is a chronic inflammatory disease, which causes multiple complications. Diabetic retinopathy (DR) is among these complications and is a dominant cause of vision loss for diabetic patients. Numerous studies have shown that chrysin, a flavonoid, has many biological activities such as anti-oxidation and anti-inflammation. However, it is rarely used in ocular diseases. In this study, we examined the inhibitory effects of flavonoid on high glucose induced migration of chorioretinal endothelial cells (RF/6A cells) and its mechanism. Materials and methods: The viability of RF/6A cells treated with chrysin was examined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The migration of RF/6A cells was assessed by the transwell migration and scratch wound assays. The expression of AKT, ERK, vascular endothelial growth factor (VEGF), HIF&minus, 1&alpha, and MMP-2 were determined by western blotting. To observe the mRNA expression of VEGF receptor (VEGFR), qRT-PCR, was utilized. Results: The results showed that chrysin can dose-dependently inhibit the RF/6A cell migration in vitro transwell and the scratch wound assays which are induced by high glucose. After pretreatment of RF/6A cells with different concentrations of chrysin, they did not produce any cytotoxicity in MTT assay. Moreover, chrysin down-regulated both phosphorylated AKT and ERK, as well as attenuated the expression levels of MMP-2. It also decreased the expression of the VEGF transcription factor and VEGF. Furthermore, it was shown that chrysin could suppress the protein and mRNA expression levels of VEGFR. Conclusion: The results indicate that chrysin could down-regulate the phosphorylation of AKT, ERK and MMP-2 and reduce the effects of VEGF and VEGFR in a high glucose environment. It further inhibits the high glucose-induced migration of RE/6A cells. Therefore, chrysin may have the potential for visual protection.

Huey-Ming Lo,1,2 Ming-Chieh Ma,1 Jiunn-Min Shieh,3,4 Hui-Ling Chen,5 Wen-Bin Wu1 1School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 2Section of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 3Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan; 4Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 5Holistic Education Center, Fu-Jen Catholic University, New Taipei City, Taiwan Introduction: Vascular smooth muscle cells (VSMCs) play an important role in the development and progression of atherosclerosis and vascular injuries in terms of proliferation and migration. Therefore, the aim of this study was to investigate the anti-migratory and proliferative effects of naked gold nanoparticles (AuNPs) on VSMCs. Materials and methods: One set of physically synthesized AuNPs (pAuNPs) and three sets of chemically synthesized AuNPs (cAuNPs) were tested. Results and discussion: Among them, the pAuNPs were found to significantly and markedly inhibit platelet-derived growth factor (PDGF)-induced VSMC migration. Transmission electron microscopy revealed that the pAuNPs were ingested and aggregated in the cytoplasm at an early stage of treatment, while the viability of VSMCs was not affected within 24 hours of treatment. The pAuNP treatment enhanced cellular mitochondrial activity but inhibited basal and PDGF-induced VSMC proliferation, as determined by MTT, WST-1, and BrdU cell proliferation assays. Furthermore, the pAuNPs did not interfere with PDGF signaling or matrix metalloproteinase-2 expression/activity. Unlike the cAuNPs, the pAuNPs could markedly reduce VSMC adhesion to collagen, which was supported by the findings that the pAuNPs could inhibit collagen-induced tyrosine protein and focal adhesion kinase (FAK) phosphorylation and actin cytoskeleton reorganization during cell adhesion. The in vitro effects of the pAuNPs were confirmed in the invivo rat balloon-injured carotid artery model by diminishing the proliferating VSMCs. Conclusion: Taken together, the present study provides the first evidence that naked pAuNPs can reduce VSMC migration and compromise cell adhesion by affecting FAK and tyrosine-protein activation. The pAuNPs also have an inhibitory effect on PDGF-induced VSMC proliferation and can reduce proliferating/migrating VSMC expression in vivo. Keywords: adhesion, AuNP, cardiovascular disease, FAK, platelet-derived growth factor, VSMC, TEM

Aims The exact world-wide prevalence of Brugada electrocardiogram (ECG) pattern is still unclear, especially in adults aged 55 years and older. Methods and results The study was conducted as part of the Healthy Aging Longitudinal Study in Taiwan (HALST). Using a stratified random sampled method, a sample of community-dwelling subjects was recruited from seven community-based regions across Taiwan. All enrolled subjects were follow-up annually and cause of death was documented by citizen death records. A total of 5214 subjects were enrolled (male/female: 2530/2684) with a mean age of 69 ± 8 years. The overall prevalence of Brugada ECG patterns was 3.32%. Four subjects carried spontaneous Type 1 Brugada ECG pattern, 68 carried Type 2, and 101 carried Type 3. Compared with the world-wide average prevalence of Brugada ECG patterns, the prevalence of spontaneous Type 1 Brugada ECG pattern in subjects from the HALST cohort was similar (0.077 vs. 0.07%) and the combined prevalence of Types 2 and 3 Brugada ECG pattern was 10 times higher (3.24 vs. 0.28%) even the mean age of study subjects was significantly higher (69 ± 8 vs. 35 ± 8, P < 0.001). However, all-cause mortality and cardiac mortality rates were not significantly different between subjects with and without Brugada ECG patterns during the 4-year follow-up (log-rank test, P = 0.21, 0.32, respectively). Conclusion The prevalence of Brugada ECG pattern in adults aged 55 years and older in Taiwan was higher than the average world-wide prevalence but was not associated with increased mortality.

Aims To investigate whether renal dysfunction is a useful predictor of postoperative atrial fibrillation (POAF) after cardiac surgery. We also aimed to determine whether the addition of renal dysfunction into the scoring system could improve diagnostic accuracy of the CHA2DS2-VASc score to predict POAF. Methods and results The study prospectively enrolled 350 consecutive patients who underwent cardiac surgery. Echocardiography was performed before cardiac surgery. Renal dysfunction was defined as estimated glomerular filtration rate < 60 mL min−1 1.73 m−2. All patients were monitored with continuous electrocardiographic telemetry for the occurrence of POAF until the day of hospital dismissal. Postoperative atrial fibrillation occurred in 103 of 350 patients (29%). Patients with POAF was associated with longer intensive care unit stay compared with those without POAF (3.7 ± 2.2 vs. 3.1 ± 1.4 days, P = 0.002). Both the CHA2DS2-VASc score and renal dysfunction were independent predictors of POAF in multivariate analysis. Renal dysfunction can further stratify patients with a CHA2DS2-VASc score of 0 or 1 into two groups with different POAF rates (3.1% vs. 68.8%, P < 0.001). A new scoring system (R-CHA2DS2-VASc score) derived by assigning an additional point representing renal dysfunction to the CHA2DS2-VASc score could improve its predictive accuracy. The area under the receiver operating characteristic curve increased from 0.68 to 0.71 ( P < 0.001). Furthermore, the rate of left ventricular diastolic dysfunction also increased with increasing renal dysfunction. Conclusion Renal dysfunction, associated with left ventricular diastolic dysfunction, was a significant risk factor for POAF after cardiac surgery and may improve the diagnostic accuracy of the CHA2DS2-VASc score.

We assessed the prognostic implications of low triiodothyronine (T3) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in critically ill patients with acute heart failure. We acquired data for 144 critical care patients with acute decompensated heart failure, of which 106 were included in this study. Plasma thyroid hormones and NT-proBNP levels were determined within 48 hours of admission. We assessed these measures for predicting all-cause and cardiac mortalities. At a mean follow-up period of 25 ± 31 months, the all-cause mortality rate was 51% (54 of 106) and the cardiac mortality rate was 70% (38 of 54). A multivariate Cox regression model showed that log-transformed NT-proBNP levels (log NT-proBNP; hazard ratio [HR] 2.90, 95% confidence interval [CI] 1.38 to 6.08, p = 0.005) and T3 levels (HR 0.98, 95% CI 0.96 to 0.99, p = 0.008) were associated with all-cause mortality, and log NT-proBNP (HR 3.70, 95% CI 1.28 to 10.71, p = 0.02) and T3 (HR 0.98, 95% CI 0.96 to 0.99, p = 0.01) were associated with cardiac mortality. Based on cut-off values for NT-proBNP (10,685 pg/ml) and T3 (52.3 ng/dl), Kaplan-Meier analyses provided significant prognostic information with the highest risk for all-cause mortality in the low T3 (≤52.3 ng/dl)/high NT-proBNP (10,685 pg/ml) group (HR 8.54, 95% CI 4.19 to 17.40, p0.0001). In conclusion, T3 levels appear to be independent predictors for both all-cause and cardiac mortalities among critical ill patients with heart failure, and high NT-proBNP and low T3 levels predict a worse long-term outcome.

Previous studies have demonstrated that vitamin A and carotenoids regulate immune function in lymphocytes and splenocytes, and that the carotenoid lutein regulates matrix metalloproteinase-9 (MMP-9) production in macrophages. In this study, we investigated the effects of all-trans retinoic acid (atRA, a bioactive vitamin A metabolite), retinol (vitamin A), and β-carotene (vitamin A precursor) on the activity of murine RAW264.7 and peritoneal macrophages. Our results indicated that atRA and retinol could induce GM-CSF and IL-16 expression, whereas all these tested substances enhanced MMP-9 production. Interestingly, the expression of GM-CSF, IL-16, and MMP-9 was distinctly regulated by these three substances. AtRA and retinol affected GM-CSF and IL-16 expression mainly through RA receptor β (RARβ). However, atRA induced MMP-9 production was via RARα activation and retinol and β-carotene caused MMP-9 production via RARα and β activation. These were supported by the observations that the RARα and β agonists/antagonists differentially affected MMP-9 production and that atRA and β-carotene enhanced RARE-mediated and MMP-9 promoter luciferase activity. In parallel, while the MMP-9 induction by atRA was not affected by the MAPKs inhibitors, its induction by retinol and β-carotene was repressed by the inhibitor targeting ERK1/2. Finally, we show that all the tested substances could functionally enhance macrophage phagocytosis. Taken together, we provide evidence here for the first time that atRA, retinol, and β-carotene differentially regulate GM-CSF, IL-16, and MMP-9 production in macrophages, explaining at least in part why these vitamin A-related substances are beneficial for immunity.

Aims/Introduction Admission hyperglycemia is associated with poor outcome in patients with myocardial infarction. The present study evaluated the relationship between admission glucose level and other clinical variables in patients with ST‐elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Materials and Methods The 959 consecutive STEMI patients undergoing primary PCI were divided into five groups based on admission glucose levels of

Carotenoid lutein causes MMP-9 release that participates in macrophage phagocytosis. Early studies have demonstrated the ability of dietary carotenoids to enhance immune response, but the mechanism underlying their influence on macrophage activity remains unclear. Here, we investigated the effects of carotenoids on macrophage activity. Carotenoids, including lutein and lycopene, enhanced MMP-9 activity in RAW264.7 macrophages. Lutein was chosen as a representative and analyzed further in this study. It increased the synthesis, activity, and release of MMP-9 in murine RAW264.7 and primary-cultured peritoneal macrophages. MMP-9 induction by lutein was through the transcriptional regulation of mmp-9. It was blunted by the MAPK inhibitors targeting ERK1/2 and p38 MAPK, the reagents that inhibit free radical signaling, and the inhibitors and siRNA targeting RARβ. Moreover, lutein induced Nox activation and intracellular ROS production at an early stage of treatment. This carotenoid also caused ERK1/2 and p38 MAPK activation, RARβ expression, and RAR interaction with its responsive element in the promoter region. These findings suggest the involvement of ROS, MAPKs, and RARβ activation in lutein-driven MMP-9 expression and release. Interestingly, lutein enhanced the phagocytic activity of macrophages, and the secreted MMP-9 appeared to be involved in this process. In summary, we provide evidence here for the first time that the carotenoid lutein induces intracellular ROS generation and MAPK and RARβ activation in macrophages, leading to an increase in MMP-9 release and macrophage phagocytosis. Our results demonstrate that lutein exerts an immunomodulatory effect on macrophages.

Background: Renal dysfunction is associated with a higher rate of atrial fibrillation in clinical practice. This study investigated the associations between renal function, left ventricular (LV) diastolic dysfunction, and postoperative atrial fibrillation (POAF). Methods and Results: A total of 265 consecutive patients who underwent cardiac surgery were prospectively enrolled in the study. Echocardiography was performed before cardiac surgery. The patients were divided into 3 groups based on estimated glomerular filtration rate (eGFR) (group 1, ≥90ml·min–1·1.73m–2; group 2, 60–90ml·min–1·1.73m–2; and group 3, 15 – also increased (group 1, 19.0%; group 2, 38.1%; and group 3, 48.3%; P

The activation of endothelial cells (ECs) and migration of vascular smooth muscle cells (VSMCs) have played a crucial role in monocyte chemotaxis/adhesion and intima thickening during vascular injury and atherosclerosis, respectively. Several phenanthrenes isolated from plants and natural products have been shown to possess different bioactivities such as anti-platelet aggregation and anti-inflammation. The current study was designated to investigate the effects of a phenanthrene derivative, 5,7-dimethoxy-1,4-phenanthrenequinone (DMPQ), on cell adhesion molecule (CAM) expression in vascular ECs and migration in VSMCs. The DMPQ attenuated monocyte-EC interaction but it did not affect monocyte adhesion to matrix. In parallel, DMPQ reduced tumor necrosis factor-α (TNF-α)-induced intercellular adhesion molecule and vascular CAM expression in ECs. DMPQ compromised TNF-α-induced IκB activation, nuclear factor-kappa B (NF-κB) translocation, and NF-κB-DNA complex formation. Moreover, it affected TNF-α- and hydrogen peroxide (H2O2)-induced reactive oxygen species production and IκB activation. These suggest that DMPQ affects CAM expression by affecting NF-κB signaling. Meanwhile, DMPQ could also inhibit platelet-derived growth factor (PDGF)-induced VSMC migration toward collagen by affecting cellular PDGF signaling, including PDGFRβ, PLCγ, ERK1/2, and Akt phosphorylation. The VSMC adhesion to collagen and collagen-induced focal adhesion kinase activation during cell adhesion were impaired by DMPQ treatment. This study reveals a phenanthrene derivative-DMPQ-with anti-inflammatory and anti-migratory bioactivity toward vascular ECs and SMCs, suggesting its protective effect on vascular injuries.

Background Chemerin, a novel adipokine, plays a role in the inflammation status of vascular endothelial cells. Hypoxia causes endothelial-cell proliferation, migration, and angiogenesis. This study was aimed at evaluating the protein and mRNA expression of chemerin after exposure of human coronary artery endothelial cells (HCAECs) to hypoxia. Methods and Results Cultured HCAECs underwent hypoxia for different time points. Chemerin protein levels increased after 4 h of hypoxia at 2.5% O2, with a peak of expression of tumor necrosis factor-alpha (TNF-alpha) at 1 h. Both hypoxia and exogenously added TNF-alpha during normoxia stimulated chemerin expression, whereas an ERK inhibitor (PD98059), ERK small interfering RNA (siRNA), or an anti-TNF-alpha antibody attenuated the chemerin upregulation induced by hypoxia. A gel shift assay indicated that hypoxia induced an increase in DNA-protein binding between the chemerin promoter and transcription factor SP1. A luciferase assay confirmed an increase in transcriptional activity of SP1 on the chemerin promoter during hypoxia. Hypoxia significantly increased the tube formation and migration of HCAECs, whereas PD98059, the anti-TNF-alpha antibody, and chemerin siRNA each attenuated these effects. Conclusion Hypoxia activates chemerin expression in cultured HCAECs. Hypoxia-induced chemerin expression is mediated by TNF-alpha and at least in part by the ERK pathway. Chemerin increases early processes of angiogenesis by HCAECs after hypoxic treatment.

The newer 256-slice computed tomography coronary angiography (CTCA) has the capability of improving diagnostic performance in the detection of obstructive coronary artery disease (CAD) compared to 64-slice CTCA. The aim of this study was to compare the diagnostic performance of 64- versus 256-slice CTCA in two similar populations.Our study included 120 consecutive patients who were referred for CTCA and subsequently underwent conventional coronary angiography (CCA). Sixty patients were studied by 64-slice CTCA, with the other 60 by 256-slice CTCA. We compared the technical characteristics and diagnostic performance of 64- and 256-slice CTCA for the detection of ≥ 50% stenosis of the coronary arteries on CCA.The 256-slice CTCA had a shorter scanning time (4.4 ± 0.6 sec vs. 5.0 ± 0.7 sec, p0.001) compared to 64-slice CTCA. The diagnostic accuracy rates of 256-slice CTCA based on patient analysis (97% vs. 83%, p0.05), vessel analysis (95% vs. 85%, p0.05), and segment analysis (94% vs. 88%, p0.05) were significantly superior to those of 64-slice CTCA. The diagnostic accuracy rates of 64- and 256-slice CTCA were affected by the presence of stent (65% vs. 75%, respectively, p0.05) and severe calcifications (75% vs. 82%, respectively, p0.05).In two similar populations, 256-slice CTCA displayed superior diagnostic performance than 64-slice CTCA. However, the performance of 256-slide CTCA is affected in those segments that are severely calcified and/or stented.Computed tomography coronary angiography (CTCA); Conventional coronary angiography; Diagnostic performance; 64-slice helical CTCA; 256-slice helical CTCA.

BackgroundMicroRNAs play an important role in cardiac remodeling. MicroRNA 499 (miR499) is highly enriched in cardiomyocytes and targets the gene for Calcineurin A (CnA), which is associated with mitochondrial fission and apoptosis. The mechanism regulating miR499 in stretched cardiomyocytes and in volume overloaded heart is unclear. We sought to investigate the mechanism regulating miR499 and CnA in stretched cardiomyocytes and in volume overload-induced heart failure.Methods & resultsRat cardiomyocytes grown on a flexible membrane base were stretched via vacuum to 20% of maximum elongation at 60 cycles/min. An in vivo model of volume overload with aorta-caval shunt in adult rats was used to study miR499 expression. Mechanical stretch downregulated miR499 expression, and enhanced the expression of CnA protein and mRNA after 12 hours of stretch. Expression of CnA and calcineurin activity was suppressed with miR499 overexpression; whereas, expression of dephosphorylated dynamin-related protein 1 (Drp1) was suppressed with miR499 overexpression and CnA siRNA. Adding p53 siRNA reversed the downregulation of miR499 when stretched. A gel shift assay and promoter-activity assay demonstrated that stretch increased p53 DNA binding activity but decreased miR499 promoter activity. When the miR499 promoter p53-binding site was mutated, the inhibition of miR499 promoter activity with stretch was reversed. The in vivo aorta-caval shunt also showed downregulated myocardial miR499 and overexpression of miR499 suppressed CnA and cellular apoptosis.ConclusionThe miR499-controlled apoptotic pathway involving CnA and Drp1 in stretched cardiomyocytes may be regulated by p53 through the transcriptional regulation of miR499.

Platelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of smooth muscle cells (SMCs) and fibroblasts. Abnormalities of PDGF/PDGF receptor (PDGFR) are thought to contribute to vascular diseases and malignancy. We previously showed that natural carotenoid lycopene can directly bind to PDGF-BB and affect its related functions in vascular SMCs. In this study we examined lycopene effect on PDGF-AA/-AB-induced signaling and migration in SMCs and fibroblasts. We found that lycopene inhibited PDGF-AA-induced SMC and fibroblast migration in a concentration-dependent manner. Lycopene reduced PDGF-AA signaling, including phosphorylation in PDGFR-alpha and its downstream protein kinases/enzymes. It also inhibited PDGF-AB-induced signaling and cell migration. However, lycopene did not affect PDGF-induced reactive oxygen species production and H2O2-induced PDGFR phosphorylation. The binding analysis revealed that lycopene but not beta-carotene could directly bind to PDGF-AA in vitro and in plasma and this binding competitively inhibited lycopene interaction with PDGF-BB, suggesting that lycopene bound to PDGF-AA/-BB at a homologous/similar region within PDGF. Moreover, the docking and binding analyses predicted that the lycopene-binding region within PDGF was located at loop 2 region. Taken together, we provide here evidence that lycopene interacts with PDGF-AA/-AB and compromises their intracellular signaling, leading to a marked inhibition on PDGF-AA/-AB-induced migration in both SMCs and fibroblasts. We also predicted its binding region within PDGF and proved its anti-vascular injury effect in vivo. The results, together with our previous findings, suggest lycopene special affinity/effect for PDGF family and its possible application in prevention in vascular diseases and malignancy.

Aims To assess the diagnostic accuracy of 256-row computed tomographic angiography (CTA) in patients with suspected coronary artery disease (CAD). Non-invasive imaging of the coronary artery by CTA has increasingly been used in recent years. The accuracy of 256-row CTA has not yet been studied. We sought to assess the accuracy of 256-row CTA compared with invasive coronary angiography (ICA) in the diagnosis and assessment of CAD. Methods and results We prospectively evaluated 104 consecutive individuals who accepted CTA and then underwent ICA. The presence of stenosis ≥50% was considered obstructive. The diagnostic accuracy of CTA for detecting obstructive stenosis was compared with that of ICA. The area under the receiver-operating-characteristic curve (AUC) was used to evaluate the diagnostic accuracy of CTA relative to ICA. A total of 86 patients had obstructive CAD. The patient-based analysis of CTA for detecting stenosis ≥50% according to ICA revealed an AUC of 0.744 [95% confidence interval (CI), 0.572–0.916], with a sensitivity of 98.8%, a specificity of 50%, a positive predictive value (PPV) of 92.4%, and a negative predictive value (NPV) of 87.5%. The segment-based analysis revealed an AUC of 0.915 (95% CI, 0.847–0.982), with a sensitivity of 93.5%, a specificity of 95%, a PPV of 77.6%, and an NPV of 98.7%. The vessel-based analysis revealed an AUC of 0.887 (95% CI, 0.808–0.966), with a sensitivity of 94.3%, a specificity of 87.3%, a PPV of 82.7%, and an NPV of 95.9%. Conclusion 256-Row CTA is a highly sensitive test of CAD and has a high predictive value. 256-Row CTA may be a potential alternative to detect coronary artery stenosis and rule out CAD in suspected patients.

Thrombin levels increase at sites of vascular injury and during acute coronary syndromes. It is also increased several fold by sepsis with a reciprocal decrease in the anti-thrombin III levels. In this study we investigate the effects of thrombin on the induction of cyclooxygenase-2 (COX-2) and prostaglandin (PG) production in macrophages. Thrombin-induced COX-2 protein and mRNA expression in RAW264.7 and primary cultured peritoneal macrophages. A serine proteinase, trypsin, also exerted a similar effect. The inducing effect by thrombin in macrophages was not affected by a lipopolysaccharide (LPS)-binding antibiotic, polymyxin B, excluding the possibility of LPS contamination. The increase of COX-2 expression by thrombin was functionally linked to release of PGE2 and PGI2 but not thromboxane A2 into macrophage culture medium. Thrombin-induced COX-2 expression and PGE2 production were significantly attenuated by PD98059 and SB202190 but not by SP600125, suggesting that ERK1/2 and p38 MAPK activation were involved in this process. This was supported by the observation that thrombin could directly activate ERK1/2 and p38 MAPK in macrophages. A further analysis indicated that the proteinase-activated receptor 1 (PAR1)-activating agonist induced effects similar to those induced by thrombin in macrophages and the PAR1 antagonist-SCH79797 could attenuate thrombin-induced COX-2 expression and PGE2 release. Taken together, we provided evidence demonstrating that thrombin can induce COX-2 mRNA and protein expression and PGE2 production in macrophages through PAR1 activation and ERK1/2 and p38 MAPK-dependent pathway. The results presented here may explain, at least in part, the possible contribution of thrombin and macrophages in these pathological conditions. J. Cell. Biochem. 108: 1143–1152, 2009. © 2009 Wiley-Liss, Inc.

To study the association of renin gene polymorphism with essential hypertension in the Chinese population, 86 hypertensive and 107 normotensive subjects were enrolled from an epidemiologic survey. Leukocyte DNA was extracted and digested with Hind III and Bgl I restriction enzymes. Southern hybridization was done with digoxigenin-incorporated renin gene probes generated by polymerase chain reaction. The restriction fragments were detected by anti-digoxigenin antibody and enzyme methods. Two Hind III polymorphysms of the renin gene (8.7 kb and 6.2 kb) were identified. The allele frequences were 129(75%) and 43(25%), respectively, in hypertensives; they were 139(65%) and 75(35%), respectively, in normotensives (chi2 = 4.074, p = 0.044). The genotypes of 8.7/8.7,8.7/6.2 and 6.2/6.2 were significantly different between hypertensives and normotensives, being 45(52%), 39(45%), 2(3%) and 48(45%), 43(40%), and 16(15%), respectively (chi2 = 9.002, p = 0.11). The Bgl I polymorphism did not show a difference between hypertensives and normotensives. Thus, we conclude that the renin gene Hind III polymorphysm is associated with hypertension in this Chinese population.

Summary Background & aims Subjects with obesity had autonomic nervous abnormalities. This study investigated autonomic nervous modulation in subjects with obesity and its association with the indices of obesity, especially the body mass index and waist circumference, by heart rate variability analysis. Methods Forty-seven adults with a body mass index (in kg/m2) greater than 28 were recruited as the obese group and 30 subjects with a body mass index less than 23 were recruited as the control group. Anthropometric measures and heart rate variability measures were obtained for both groups. The correlation between heart rate variability measures and the anthropometric measures was assessed in subjects with obesity. Results Subjects with obesity had lower normalized low-frequency power and normalized high-frequency power than those of the control group. The body height, body weight, waist circumference and waist-to-hip ratio correlated significantly with the spectral heart rate variability measures in Asian subjects with obesity, whereas the body mass index did not. Conclusions Abdominal obesity, rather than general obesity, was related to autonomic nervous derangement in Asian subjects with obesity. The close relation between abdominal obesity and autonomic derangement may partially account for the close relationship between abdominal obesity and higher risk of mortality and morbidity in subjects with obesity.

Cardiovascular diseases (CVDs) result from the sub-endothelial accumulation of inflammatory cells and smooth muscle cells (SMCs). Lycopene, a natural compound from tomato, has been suggested to play a role in CVD prevention. However, its action mechanism is still largely unknown. In this study, we examined the effect of lycopene on SMCs. We found that preincubation of PDGF-BB with lycopene resulted in a marked inhibition on PDGF-BB-induced PDGF receptor-beta (PDGFR-beta), PLCgamma, and ERK1/2 phosphorylation in rat A10 SMCs and primary cultured aortic SMCs. In striking contrast, lycopene did not influence EGF-induced ERK1/2 phosphorylation. Surprisingly, further analysis indicates that lycopene could directly bind PDGF-BB and inhibit PDGF-BB-SMC interaction, as determined by dot binding assay and Western blotting. In functional studies, lycopene inhibited PDGF-BB-induced SMC proliferation and migration toward gelatin and collagen at concentrations ranging from 2 to 10 microM. On the contrary, lycopene did not inhibit bFGF- and VEGF-induced endothelial cell migration. Gelatin zymography demonstrated that lycopene's effect on SMC migration was not due to the inhibition of matrix metalloproteinases (MMPs). Taken together, our results provide the first evidence showing that lycopene inhibits PDGF-BB-induced signaling, proliferation and migration in rat A10 and aortic SMCs. One of the action mechanisms is that lycopene is capable of binding PDGF-BB and inhibiting its interaction with SMC, which is quite different from those previously developed PDGFR-beta antagonists. The results presented here may help us to better understand the beneficial effects of lycopene in CVD prevention.

Occlusive lesions of atherosclerosis are the consequence of focal accumulation within the innermost layer of the artery of leukocytes from the circulation and smooth muscle cells (SMCs) from the underlying media. Tea polyphenol especially (-)-Epigallocatechin-3-gallate (EGCG) has been shown to have cardiovascular protective effect. However, the effects of other catechins such as (+)-catechin, and (-)-epicatechin-3-gallate (ECG) on SMC's functions have not been fully understood. In the present study, we investigate the effects of tea catechins on SMC adhesion and migration. Our results indicate that EGCG and ECG but not (+)-catechin were able to inhibit SMC adhesion on collagen and laminin, two abundant extracellular matrix (ECM) proteins expressed in physiological and pathological conditions. Further analyses indicate that EGCG could bind laminin more than collagen. Moreover, EGCG could inhibit SMC adhesion to integrin beta1 Ab and affect SMC's beta1 integrin expression, suggesting it affects SMC's cellular components. In migration experiment, laminin- and PDGF-BB-induced SMC migration were both inhibited by EGCG in a dose-dependent manner. Taken together, the data presented here provide evidence showing that among these tea catechins, EGCG and ECG are relatively effective inhibitors on SMC-ECM interaction and their action mechanisms are through interference with SMC's integrin beta1 receptor and binding to ECM proteins.

CHA2 DS2 -VASc score has been proven to have great prognostic value in patients with acute coronary syndrome (ACS). We aimed to determine whether the addition of renal dysfunction in the CHA2 DS2 -VASc score would improve the prognostic impact of the scoring system to predict prognosis among ACS patients.A total of 3031 ACS patients were prospectively enrolled at 39 hospitals and followed for 1 year. The patients were divided into three groups based on estimated glomerular filtration rate (eGFR) (group 1, eGFR90; group 2, eGFR between 60 and 90; and group 3, eGFR60 mL/min per 1.73 m(2) ). The occurrence of subsequent myocardial infarction (MI), stroke, or death was recorded.As renal function progressively decreased from group 1 to 3, the patients were, respectively older and had higher incidence of comorbidity, worse Killip classification, and less evidence-based medical therapies. The rate of subsequent MI, stroke or death increased from 3.4% in group 1 to 7.4% in group 2 and 17.2% in group 3 (P 0.001). Renal dysfunction (eGFR60 mL/min per 1.73 m(2) ) and CHA2 DS2 -VASc scores were both significant predictors of adverse events in multivariable regression analyses. Renal dysfunction can further stratify patients with CHA2 DS2 -VASc score of 0 or 1 into 3 groups with different adverse event rates (group 1, 3.0%; group 2, 4.1%; and group 3, 9.2%, P 0.001). A new scoring system (R-CHA2 DS2 -VASc score) derived by assigning one more point for eGFR ≤ 60 mL/min per 1.73 m(2) to the CHA2 DS2 -VASc score could improve its predictive accuracy (area under the receiver operating curve, 0.70 vs. 0.66, P 0.001).Renal dysfunction is a significant risk factor of future adverse events in ACS patients and may improve the prognostic impact of the CHA2 DS2 -VASc score.

It has been reported that ultraviolet B (UVB) irradiation causes the loss of E-cadherin of melanocytes, leading them to escape from neighboring keratinocytes during melanoma development. However, little has been paid on its effect on E-cadherin of keratinocytes. In the present study we therefore focus on whether UVB affects expression of E-cadherin-catenin complex in human HaCaT keratinocytes. We found that E-cadherin, beta-, and gamma-catenin but not alpha-catenin were proteolytically cleaved in UVB-irradiated HaCaT keratinocytes. The effect was only observed in keratinocyte undergoing apoptosis. Cleavage of beta- and gamma-catenin was fully abolished by caspase-3 and caspase-8 inhibitors, whereas cleavage of E-cadherin was inhibited by neither caspase nor metalloproteinase inhibitors. Functional analysis showed that the cleavage resulted in the disruption of the physical association between E-cadherin and catenins, indicating that E-cadherin signaling was compromised in UVB-irradiated HaCaT keratinocytes. Because E-cadherin in keratinocytes plays important roles in mediating cell-cell adhesion in epidermis of skin, the loss of E-cadherin and signaling components in keratinocytes may lead to the disruption of skin integrity after UVB exposure.

Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations.

In recent studies, aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that can prevent the age-related aortic stiffening and cardiac hypertrophy. The aim of this study was to determine whether AG had effects on the left ventricular (LV)-arterial coupling in aged Fisher 344 rats in terms of the ventricular and arterial chamber properties. Normotensive rats were treated from 18 to 24 months with AG (1 g l(-1) in drinking water) and compared with a control group. LV pressure and ascending aortic flow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (Ees) and effective arterial volume elastance (Ea), respectively. The optimal afterload (Qload) determined by the ratio of Ea to Ees was used to measure the efficiency of mechanical energy transferred from the left ventricle to the arterial system. In comparison with the 6-month-old rats, the 24-month-old animals had decreased Ees, at 567.4 +/- 26.7 vs 639.0 +/- 20.7 mmHg ml(-1), decreased Ea, at 411.5 +/- 18.6 vs 577.9 +/- 15.7 mmHg ml(-1), and decreased Q(load), at 0.9428 +/- 0.0024 vs 0.9962 +/- 0.0014. Treatment with AG for 6 months did not significantly affect Ees; however, when normalized to LV weight (i.e., Eesn = Ees/LV weight), Eesn showed a significant rise of 22.8%, suggesting that AG may retard the aging process on the intrinsic contractility of the left ventricle. On the other hand, the decrease in Ea in aging rats was prevented by AG, as reflected in the increase of 19.7% in this variable (P < 0.05). The 24-month-old treated rats also exhibited a significant rise of 21.6% in Ea/Ees, causing an increase of 5.2% in Qload (P < 0.05). We conclude that in healthy older Fisher 344 rats without diabetes, long-term treatment with AG may improve both the arterial and ventricular function and optimize the matching condition for the left ventricular-arterial coupling.

Surgically induced abnormalities in atrial conduction could result in unusual P wave changes. A 31-year-old woman underwent concomitant mitral valve surgery and atrial compartment operation for mitral stenosis and atrial fibrillation (AF). After operation, the AF was successfully converted to sinus rhythm, whereas an unusual electrocardiogram (ECG) with a discrete negative deflection before the T wave in V1 was noted. Electrophysiological study showed a marked conduction delay from the high right atrium (HRA) to the right atrial appendage (RAA) compartment, which resulted in a separation of P waves. The P wave preceding the QRS complex represented the activation of sinus node and the left atrial compartments, and the P at the vicinity of T wave represented the activation of RAA compartment. The conduction from HRA to RAA was worsened on HRA pacing at a faster rate, and improved after isoproterenol infusion. This report demonstrated that conduction across a surgically created isthmus in the atrium could be severely impaired and result in unusual P wave separation.

We determined the roles of maximal systolic elastance (Emax) and theoretical maximum flow (Qmax) in the regulation of cardiac pumping function in early streptozotocin (STZ)-diabetic fats. Physically, Emax can reflect the intrinsic contractility of the myocardium as an intact heart, and Qmax has an inverse relation to the systolic resistance of the left ventricle. Rats given STZ 65 mg/kg l.v. (n = 17) were divided into two groups, 1 week and 4 weeks after induction of diabetes, and compared with untreated age-matched controls (n = 15). Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate Emax and Qmax, using the elastance-resistance model. After 1 or 4 weeks, STZ-diabetic animals show an increase in effective LV end-diastolic volume (Veed), no significant change in peak iso-volumic pressure (Pisomax), and a decline in effective arterial volume elastance (Ea). The maximal systolic elastance Emax is reduced from 751.5 ± 23.1 mmHg/ml in controls to 514.1 ± 22.4 mmHg/ml in 1- and 538.4 ± 33.8 mmHg/ml in 4-week diabetic rats. Since Emax equals PisomaxVeed, an increase in Veed with unaltered Pisomax may primarily act to diminish Emax so that the intrinsic contractility of the diabetic heart is impaired. By contrast, STZ-diabetic rats have higher theoretical maximum flow Qmax (40.9 ± 2.8 ml/s in 1- and 44.5 ± 3.8 ml/s in 4-week diabetic rats) than do controls (30.7 ± 1.7 ml/s). There exists an inverse relation between Qmax and Ea when a linear regression of Qmax on Ea is performed over all animals studied (r= 0.65, p < 0.01). The enhanced Qmax is indicative of the decline in systolic resistance of the diabetic rat heart. The opposing effects of enhanced Qmax and reduced Emax may negate each other, and then the cardiac pumping function of the early STZ-diabetic rat heart could be preserved before cardiac failure occurs.

Background MicroRNAs (miRs) play a role in cardiac remodelling, and acute myocardial infarction (AMI) can regulate miR expression. MiR-208a is essential for the expression of the genes involved in cardiac hypertrophy and fibrosis. MiR-208a activates endoglin expression and may result in cardiac fibrosis. The role of miR-208a and endoglin in AMI is not known. We sought to investigate the regulation of miR-208a and endoglin in AMI. Methods Ligation of the proximal left anterior descending artery was performed in adult Sprague-Dawley rats to induce AMI. Echocardiography was used to measure heart size and left ventricular function. The TaqMan miR real-time quantitative assay was used to quantitate miR-208a. Myocardial fibrosis was detected by Masson trichrome staining. Results AMI and overexpression of miR-208a in the sham group without infarction significantly increased myocardial miR-208a, endoglin, and β-myosin heavy chain (β-MHC) expression. Overexpression of antagomir-208a significantly inhibited the increase of myocardial endoglin and β-MHC protein expression induced by infarction. Overexpression of mutant miR-208a in the sham group did not induce myocardial endoglin and β-MHC expression. Pretreatment with atorvastatin and the angiotensin-receptor antagonist valsartan significantly attenuated the increase of endoglin and β-MHC induced by infarction. AMI and overexpression of miR-208a in the sham group significantly increased the area of myocardial fibrosis compared with the sham group. Overexpression of antagomir-208a and pretreatment with atorvastatin and valsartan in the AMI group significantly decreased the area of myocardial fibrosis induced by infarction. Conclusions MiR-208a increases endoglin expression to induce myocardial fibrosis in rats with AMI. Treatment with atorvastatin and valsartan can decrease myocardial fibrosis induced by AMI through attenuating miR-208a and endoglin expression.

Chemokines usually direct the movement of circulating leukocytes to sites of inflammation or injury. CXCL1/GRO-α has been shown to be upregulated in atherosclerotic lesions and various cancers. The aim of this study was to investigate the mechanisms underlying the TNF-α-induced release of CXCL1 from human vascular endothelial cells in vitro.Human umbilical vein endothelial cells (HUVECs) were treated with different proinflam-matory mediators and growth factors. CXCL1 expression and secretion were determined using RT-PCR and ELISA, respectively. TNF-α-induced cell signaling was assayed with Western blotting. Cell viability/growth was determined using MTT assay. Monocyte migration was measured with transwell migration assay.Among the 17 mediators and growth factors tested, TNF-α, LPS and thrombin induced marked increase in CXCL1 release from HUVEC cells. TNF-α (2, 5 ng/mL) induced CXCL1 release and mRNA expression in the cells in concentration- and time-dependent manners. TNF-α (5 ng/mL) caused activation of JNK, p38 MAPK, PI3K and Akt, whereas pretreatment with JNK inhibitor (SP600125), p38 MAPK inhibitor (SB202190) or PI-3K inhibitor (LY294002) significantly suppressed TNF-α-induced CXCL1 release from the cells. But only SP600125 significantly reduced TNF-α-induced CXCL1 mRNA expression in the cells. Moreover, dexamethasone (up to 500 nmol/L) failed to affect TNF-α-induced CXCL1 release from the cells. In functional studies, recombinant CXCL1 enhanced HUVEC proliferation, and both recombinant CXCL1 and TNF-α-induced CXCL1 from HUVECs attracted human monocyte migration.TNF-α stimulates CXCL1 release from human ECs through JNK-mediated CXCL1 mRNA expression and p38 MAPK- and PI-3K-mediated CXCL1 secretory processes.

BACKGROUND Repairing Ebstein's anomaly without correction of associated arrhythmia may result in sudden death. Catheter or surgical ablation is indicated for various symptomatic tachyarrhythmias in Ebstein's anomaly. METHODS Between October 1973 and October 1997, 30 patients with Ebstein's anomaly underwent surgical repair in our hospital. Tricuspid valve replacement was performed in 13 patients, tricuspid annuloplasty and valvuloplasty in the remaining 17 patients. Preoperative electrophysiological studies were performed in 11 patients after 1980. Concomitant arrhythmia ablation was done in 10 patients: 4 for Wolff-Parkinson-White syndrome, 2 for atrioventricular (AV) nodal reentrant tachycardia, one for ventricular tachycardia and 3 for paroxysmal atrial flutter and fibrillation. RESULTS No mortality or major morbidity occurred in those patients undergoing arrhythmia intervention. There were 7 deaths in total; 6 died suddenly, and the other died of purulent mediastinitis. None of the 6 sudden deaths underwent preoperative electrophysiological evaluation. The functional recovery was good in all survivals. CONCLUSIONS We conclude that detailed preoperative electrophysiological evaluation in patients with Ebstein's anomaly is mandatory. Aggressive surgical intervention of the associated arrhythmias in addition to anatomic correction can reduce the sudden death in Ebstein's anomaly.

In order to understand the effect of aortocaval compression on autonomic nervous activity, we compared the effects of supine and upright postures on measures of heart rate variability in late pregnancy. Thirty-two women in late pregnancy and 23 nonpregnant age-matched women were studied. Both time and frequency domain heart rate variability measures were compared between the supine and upright positions, and between pregnant women and controls. The pregnant women had smaller mean RR interval, standard deviation of RR intervals and normalised high-frequency power, and a larger low- to high-frequency power ratio than nonpregnant women in the supine position. When the position was changed from upright to supine in nonpregnant women, the percentage change in the mean RR interval and normalised high-frequency power were increased, whereas the percentage change in the coefficient of variation of RR interval and low- to high-frequency power ratio were decreased. In contrast, the percentage change in normalised high-frequency power was decreased and the percentage change in low- to high-frequency power ratio was increased in pregnant women when the position was changed from upright to supine. These results indicate that the vagal enhancing effect seen in normal subjects when changing position from upright to supine was reversed in women in late pregnancy. Aortocaval compression in the supine position in pregnant women might be responsible for this reversal in the autonomic response to lying down.

Surgical treatment for atrial fibrillation is now feasible in selective cases. The aim of this study was to assess the electrophysiological properties of patients undergoing atrial compartment operation for chronic atrial fibrillation.Electrophysiological studies were performed in 20 mitral valve patients with atrial fibrillation who had been maintained in sinus rhythm for more than 1 year after atrial compartment operation. Intra-cardiac recording and programmed electrical stimulation were performed in various atrial compartments. The parameters studied included sinus node function, atrial conduction and refractoriness, atrioventricular conduction function and inducible arrhythmias if any. Intra-cardiac recordings showed that the rhythm was of sinus origin in all cases, with the earliest atrial activity located in the high right atrium. The mean sinus cycle length was 750 +/- 110 ms, AH time 106 +/- 29 ms, and HV time 53 +/- 7 ms. The sinus node function was normal in 18 patients (90%), and only two patients had prolonged sinus node recovery and sino-atrial conduction. The right atrial appendage compartment was driven by the sinus node in all patients. However, the conduction time from the high right atrium to the right atrial appendage compartment was markedly prolonged in 12 of 15 patients (80%) undergoing the three-compartment operation in which an incision was placed between the high right atrium and right atrial appendage compartments. On the other hand, the electrical activities in the left atrial compartment were much more varied. In 13 of 20 patients (65%), the left atrial compartment was driven by the sinus node; 11 of the 13 patients had a normal or mildly prolonged conduction time (ranged 75 to 146 ms), whereas two patients had a marked delay in conduction (200 ms and 266 ms, respectively). In the remaining seven patients, the left atrial compartments were dissociated from the rest of the heart; five of them had a quiescent left atrium, one a fluttering left atrial rhythm, and one a slow left atrial rhythm. The effective refractory period was longer in the left atrial compartment (242 +/- 47 ms) as compared to that of the high right atrium (224 +/- 26 ms, P0.01) and right atrial appendage compartments (219 +/- 25 ms, P0.01). Programmed electrical stimulation could not induce atrial fibrillation in any patient, whereas two patients had inducible atrial flutter and three repetitive atrial responses.(1) Atrial compartment operation does not impair sinus node function in most cases. (2) Elimination of atrial fibrillation while maintaining the electrical connection between different atrial compartments is feasible.