The Functional Role of Myogenin in Cardiomyoblast H9c2 Cells Treated with High Glucose and Palmitic Acid: Insights into No-Rejection Heart Transplantation.

Various pathological alterations, including lipid-deposition-induced comparative cardiac lipotoxicity, contribute to cardiac aging in the failing heart. A decline in endogenous myogenin proteins can lead to the reversal of muscle cell differentiation and the creation of mononucleated muscle cells. Myogenin may be a specific regulator of adaptive responses to avoid pathological hypertrophy in the heart. Hence, it is important to understand the regulation of myogenin expression and functions in response to exposure to varied stresses. In this study, we first examined and verified the cytotoxic effect of palmitic acid on H9c2 cells. The reduction in myogenin mRNA and protein expression by palmitic acid was independent of the effect of glucose. Meanwhile, the induction of cyclooxygenase 2 and activating transcription factor 3 mRNAs and proteins by palmitic acid was dependent on the presence of glucose. In addition, palmitic acid failed to disrupt cell cycle progression when H9c2 cells were treated with no glucose. Next, we examined the functional role of myogenin in palmitic-acid-treated H9c2 cells and found that myogenin may be involved in palmitic-acid-induced mitochondrial and cytosolic ROS generation, cellular senescence, and mitochondrial membrane potential. Finally, the GSE150059 dataset was deposited in the Gene Expression Omnibus website and the dataset was further analyzed via the molecular microscope diagnostic system (MMDx), demonstrating that many heart transplant biopsies currently diagnosed as no rejection have mild molecular-antibody-mediated rejection-related changes. Our data show that the expression levels of myogenin were lower than the average level in the studied population. Combining these results, we uncover part of the functional role of myogenin in lipid- and glucose-induced cardiac cell stresses. This finding provides valuable insight into the differential role of fatty-acid-associated gene expression in cardiovascular tissues. Additionally, the question of whether this gene expression is regulated by myogenin also highlights the usefulness of a platform such as MMDx-Heart and can help elucidate the functional role of myogenin in heart transplantation.

Efficacy of a temporary CentriMag ventricular assist device in acute fulminant myocarditis patients revived with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Although extracorporeal life support (ECLS) can provide emergency systemic perfusion for acute fulminant myocarditis (AFM), the mortality rate remains extremely high, especially in those undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Temporary ventricular assist device (VAD) can provide a more physiological blood flow direction and better subsequent organ perfusion than ECLS. We investigated temporary VAD efficacy in ECPR-revived AFM patients. METHODS: During January 2012-May 2019, we retrospectively recruited 22 AFM patients with hemodynamic collapse and ECPR; 11 underwent ECLS only and 11 underwent additional VAD support after ECLS. Systemic perfusion was compared via laboratory biochemistry at post-ECPR days 2 (D2) and 4 (D4). Consciousness and cardiac function were assessed through the Glasgow Coma Scale (GCS) and echocardiography, respectively. All major complications and causes of mortality were recorded; 30-day survival was analyzed and risk factors were predicted. RESULTS: The VAD group had significantly better hemodynamic improvement; more inotropes being tapered at D2 and D4; better data representative of systemic perfusion, including albumin, pH, bicarbonate, and lactate levels at D4; and better 30-day survival (72.7% vs. 27.2%, p = 0.033). The causes of mortality included central failure, multiple organ failure, and bacteremia with sepsis. The risk factors included lethal dysrhythmia before ECLS, GCS <5 at D2, and elevated cardiac enzymes at D4. CONCLUSION: For AFM patients, temporary VAD could provide better systemic perfusion and organ preservation than ECLS. VAD had better survival, including improved recovery and successful transplantation. Hence, temporary VAD should be considered if ECLS cannot revive the sustained cardiogenic shock.

Characterization of intracellular buffering power in human induced pluripotent stem cells and the loss of pluripotency is delayed by acidic stimulation and increase of NHE1 activity.

The homeostasis of intracellular pH (pHi ) affects many cellular functions. Our previous study has established a functional and molecular model of the active pHi regulators in human induced pluripotent stem cells (hiPSCs). The aims of the present study were to further quantify passive pHi buffering power (ß) and to investigate the effects of extracellular pH and Na+ -H+ exchanger 1 (NHE1) activity on pluripotency in hiPSCs. pHi was detected by microspectrofluorimetry with pH-sensitive dye-BCECF. Western blot, immunofluorescence staining, and flow cytometry were used to detect protein expression and pluripotency. Our study in hiPSCs showed that (a) the value of total (ßtot ), intrinsic (ßi ), and CO2 -dependent ( ßCO2 ) buffering power all increased while pHi increased; (b) during the spontaneous differentiation for 4 days, the ß values of ßtot and ßCO2 changed in a tendency of decrease, despite the absence of statistical significance; (c) an acidic cultured environment retained pluripotency and further upregulated expression and activity of NHE1 during spontaneous differentiation; (d) inhibition on NHE1 activity promoted the loss of pluripotency. In conclusion, we, for the first time, established a quantitative model of passive ß during differentiation and demonstrated that maintenance of NHE1 at a higher level was of critical importance for pluripotency retention in hiPSCs.

Dipeptidyl Peptidase-4 Inhibitor Decreases Allograft Vasculopathy Via Regulating the Functions of Endothelial Progenitor Cells in Normoglycemic Rats.

PURPOSE: Chronic rejection induces the occurrence of orthotopic allograft transplantation (OAT) vasculopathy, which results in failure of the donor organ. Numerous studies have demonstrated that in addition to regulating blood sugar homeostasis, dipeptidyl peptidase-4 (DPP-4) inhibitors can also provide efficacious therapeutic and protective effects against cardiovascular diseases. However, their effects on OAT-induced vasculopathy remain unknown. Thus, the aim of this study was to investigate the direct effects of sitagliptin on OAT vasculopathy in vivo and in vitro. METHODS: The PVG/Seac rat thoracic aorta graft to ACI/NKyo rat abdominal aorta model was used to explore the effects of sitagliptin on vasculopathy. Human endothelial progenitor cells (EPCs) were used to investigate the possible underlying mechanisms. RESULTS: We demonstrated that sitagliptin decreases vasculopathy in OAT ACI/NKyo rats. Treatment with sitagliptin decreased BNP and HMGB1 levels, increased GLP-1 activity and stromal cell-derived factor 1α (SDF-1α) expression, elevated the number of circulating EPCs, and improved the differentiation possibility of mononuclear cells to EPCs ex vivo. However, in vitro studies showed that recombinant B-type natriuretic peptide (BNP) and high mobility group box 1 (HMGB1) impaired EPC function, whereas these phenomena were reversed by glucagon-like peptide 1 (GLP-1) receptor agonist treatment. CONCLUSIONS: We suggest that the mechanisms underlying sitagliptin-mediated inhibition of OAT vasculopathy probably occur through a direct increase in GLP-1 activity. In addition to the GLP-1-dependent pathway, sitagliptin may regulate SDF-1α levels and EPC function to reduce OAT-induced vascular injury. This study may provide new prevention and treatment strategies for DPP-4 inhibitors in chronic rejection-induced vasculopathy.

Huge thrombus formation in the left ventricle during bilateral CentriMag ventricular assist device with successful bridging to heart transplantation: a case report and review of the literature.

Owing to shortage of donor hearts, the ventricular assist device is used as a bridging therapy to heart transplantation. However, thrombus formation is a critical complication during ventricular assist device circulatory support that might result in ischemic infarction of end organs. Here, we report a patient diagnosed with decompensated dilated cardiomyopathy and cardiogenic shock who underwent emergent extracorporeal life support, and subsequent temporary bilateral ventricular assistance with the CentriMag device (Levitronix LLC, Waltham, MA). Daily transthoracic echocardiography did not detect any thrombus formation, and no stroke event occurred during biventricular support. During eventual orthotopic heart transplantation, transesophageal echocardiography detected a huge thrombus in the left ventricle. We removed the biventricular assist device, excised the recipient heart, cleaned up the thrombus, and then implanted the donor heart successfully. No stroke or transient neurological deficit was noted during or after the transplantation. The patient was discharged 14 days after transplantation. No major adverse cardiovascular event was noted during 2 years of outpatient follow-up.

Effects of Levosimendan on Systemic Perfusion in Patients with Low Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Score: Experience from a Single Center in Taiwan.

BACKGROUND: Patients with cardiogenic shock have a high risk of mortality. Intravenous levosimendan can provide pharmacologic inotrope support. OBJECTIVES: We aimed to investigate the effect of levosimendan in patients with extremely severe cardiogenic shock and low Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score with or without mechanical circulatory support. METHODS: From January 2017 to May 2019, 24 patients with INTERMACS 1-4 were enrolled in this retrospective study. All patients had systemic malperfusion and were treated with levosimendan. Biochemistry data related to systemic perfusion were recorded and compared before and at 24 and 72 hours after levosimendan administration. Echocardiography and Kansas City Cardiomyopathy Questionnaire (KCCQ) were completed 2 months later to assess left ventricular ejection fraction (LVEF) and quality of life (QoL), respectively. RESULTS: Arterial pressure and heart rate did not significantly differ before and after levosimendan administration. Atrial fibrillation and ventricular premature complex increased without significance. The dose of inotropes could be significantly tapered down. There were no significant differences in blood urea nitrogen, creatinine, and lactate levels. Urine output significantly increased (p = 0.018), and liver-related enzymes improved but without significance. B-type natriuretic peptide significantly decreased (p = 0.007) at 24 hours after levosimendan administration. Echocardiography showed significantly improved LVEF 2 months later (22.43 ± 8.13% to 35.87 ± 13.4%, p = 0.001). KCCQ showed significantly improved physical activity and greater relief of symptoms (p = 0.003). The survival-to-discharge rate was 75%. CONCLUSIONS: We observed a decrease in B-type natriuretic peptide, better urine output, and alleviated hepatic injury in the levosimendan group. Most patients who survived without transplantation had significantly improved LVEF and better QoL after levosimendan administration.

The effect of Sirt1 deficiency on Ca2+ and Na+ regulation in mouse ventricular myocytes.

This study addressed the hypothesis that cardiac Sirtuin 1 (Sirt1) deficiency alters cardiomyocyte Ca2+ and Na+ regulation, leading to cardiac dysfunction and arrhythmogenesis. We used mice with cardiac-specific Sirt1 knockout (Sirt1-/- ). Sirt1flox/flox mice were served as control. Sirt1-/- mice showed impaired cardiac ejection fraction with increased ventricular spontaneous activity and burst firing compared with those in control mice. The arrhythmic events were suppressed by KN93 and ranolazine. Reduction in Ca2+ transient amplitudes and sarcoplasmic reticulum (SR) Ca2+ stores, and increased SR Ca2+ leak were shown in the Sirt1-/- mice. Electrophysiological measurements were performed using patch-clamp method. While L-type Ca2+ current (ICa, L ) was smaller in Sirt1-/- myocytes, reverse-mode Na+ /Ca2+ exchanger (NCX) current was larger compared with those in control myocytes. Late Na+ current (INa, L ) was enhanced in the Sirt1-/- mice, alongside with elevated cytosolic Na+ level. Increased cytosolic and mitochondrial reactive oxygen species (ROS) were shown in Sirt1-/- mice. Sirt1-/- cardiomyocytes showed down-regulation of L-type Ca2+ channel α1c subunit (Cav1.2) and sarcoplasmic/endoplasmic reticulum Ca2+  ATPase 2a (SERCA2a), but up-regulation of Ca2+ /calmodulin-dependent protein kinase II and NCX. In conclusions, these findings suggest that deficiency of Sirt1 impairs the regulation of intracellular Ca2+ and Na+ in cardiomyocytes, thereby provoking cardiac dysfunction and arrhythmogenesis.

Cardiac calcium dysregulation in mice with chronic kidney disease.

Cardiovascular complications are leading causes of morbidity and mortality in patients with chronic kidney disease (CKD). CKD significantly affects cardiac calcium (Ca2+ ) regulation, but the underlying mechanisms are not clear. The present study investigated the modulation of Ca2+ homeostasis in CKD mice. Echocardiography revealed impaired fractional shortening (FS) and stroke volume (SV) in CKD mice. Electrocardiography showed that CKD mice exhibited longer QT interval, corrected QT (QTc) prolongation, faster spontaneous activities, shorter action potential duration (APD) and increased ventricle arrhythmogenesis, and ranolazine (10 µmol/L) blocked these effects. Conventional microelectrodes and the Fluo-3 fluorometric ratio techniques indicated that CKD ventricular cardiomyocytes exhibited higher Ca2+ decay time, Ca2+ sparks, and Ca2+ leakage but lower [Ca2+ ]i transients and sarcoplasmic reticulum Ca2+ contents. The CaMKII inhibitor KN93 and ranolazine (RAN; late sodium current inhibitor) reversed the deterioration in Ca2+ handling. Western blots revealed that CKD ventricles exhibited higher phosphorylated RyR2 and CaMKII and reduced phosphorylated SERCA2 and SERCA2 and the ratio of PLB-Thr17 to PLB. In conclusions, the modulation of CaMKII, PLB and late Na+ current in CKD significantly altered cardiac Ca2+ regulation and electrophysiological characteristics. These findings may apply on future clinical therapies.

Stimulants associated with reduced risk of hospitalization for motor vehicle accident injury in patients with obstructive sleep apnea-a nationwide cohort study.

BACKGROUND: The risk of injury directly related to hospitalization for motor vehicle accidents (MVAs) in the obstructive sleep apnea (OSA) patients has not been thoroughly understood. Our study aimed to examine the association between the OSA and the hospitalization for an MVA injury. METHODS: This retrospective cohort study used Taiwan's National Health Insurance Research Database (NHIRD) between 2000 and 2015. The OSA patients aged ≥20 years by age, sex, and index-year matched by non-OSA controls were enrolled (1:3). We used the Cox proportional regression model to evaluate the association between the OSA and the hospitalization for an MVA injury. RESULTS: The incidence rate of hospitalization for an MVA injury was higher in the OSA cohort (N = 3025) when compared with the non-OSA controls (N = 9075), as 575.3 and 372.0 per 100,000 person-years, respectively (p < 0.001). The Kaplan-Meier analysis showed that the OSA cohort had a significantly higher incidence of hospitalization for the MVA injury (log-rank test, p < 0.001). After adjusting for the covariates, the risk of hospitalization for the MVA injury among the OSA was significantly higher (hazard ratio [HR] =2.18; 95% confidence interval [CI] = 1.79-2.64; p < 0.001). Stimulants usage was associated with a nearly 20% decrease in the risk of an overall hospitalization for an MVA injury in the OSA patients. CONCLUSIONS: This study provides evidence that patients with OSA are at a two-fold higher risk of developing hospitalization for an MVA injury, and the usage of modafinil and methylphenidate was associated with a lower risk of an overall hospitalization for the MVA injury.

A Population-Based Retrospective Analysis of Post-In-Hospital Cardiac Arrest Survival after Modification of the Chain of Survival.

BACKGROUND: In 2010, the American Heart Association recommended that postcardiac arrest care should be included in the chain of survival to reduce permanent neurological damage, improve quality of life, and reduce health care expenses of postcardiac arrest care. OBJECTIVES: To investigate post-in-hospital cardiac arrest (IHCA) survival prior to and after modification of the chain of survival in 2010, with subgroup analyses per age and concomitant coronary heart disease (CHD). METHODS: We retrospectively searched the National Health Insurance Research Database for the 2007-2015 period to collect case data coded as "427.41" or "427.5" per International Classification of Disease Clinical Modification, Ninth revision codes and analyzed the data with SPSS v22.0. RESULTS: The 1-day survival rate in the 2011-2015 period was 2% higher than that in the 2007-2010 period (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04). Moreover, in the 2011-2015 period, the survival-to-discharge rate was increased by 1% in patients under 65 years (OR 1.01, 95% CI 1.00-1.02) and 1% in CHD patients (OR 1.01, 95% CI 1.01-1.02) compared with that in the 2007-2010 period. CONCLUSION: For patients with IHCA, the overall short-term survival improved significantly after modification of the chain of survival. Younger patients and patients with CHD had better long-term survival.

Wide-Angle Coronary Bifurcation Stenotic Lesions Treated With One Drug-Eluting Stent and Sequential Balloon Technique: A Better Strategy?

BACKGROUND: Clinically significant bifurcation lesions account for up to 20% of percutaneous coronary intervention (PCI) procedures, and present technical challenges due to the potential for occlusion of the side branch vessel. Percutaneous coronary intervention using final kissing ballooning (FKB) plays a major role in treating bifurcation lesions, but sequential dilatation (SD) is a less complicated PCI technique with a shallower learning curve. Previous studies have shown no benefit of FKB over SD, but wide-angle (>70°) bifurcation lesions may respond differently to narrow-angle bifurcation lesions. METHODS: Retrospective analysis was carried out to compare outcomes of FKB and SD stenting specifically for wide-angle bifurcation lesions: 7,582 PCIs performed at a single medical centre between 1 January 2009 and 31 May 2016 were screened. This yielded 112 SD and 102 FKB cases for comparative analysis, which was conducted with respect to major adverse cardiac event (MACE)-free survival and target lesion revascularisation (TLR)-free survival rates. RESULTS: The comparative analysis was achieved using the log-rank test and presented as Kaplan-Meier curves. All baseline characteristics were balanced among the groups. The mean procedure and fluoroscopy times were significantly longer for patients with FKB than SD. Patients with SD had slightly better MACE and TLR rates than those with FKB in both the drug-eluting stent (DES) and bare metal stent (BMS) groups. In addition, patients with DES had slightly lower MACE and TLR rates than those with BMS in both the FKD and SD groups. Major adverse cardiac event-free survival and TLR-free survival rates were also slightly higher in patients with DES than those with BMS in both the FKD and SD groups. However, these differences were not statistically significant. CONCLUSIONS: These results suggest that the most applicable procedure for PCI of wide-angulated bifurcation stenosis would be a combination of DES and SD.

Health Care Service Utilization After Various Vascular Access Selections.

BACKGROUND: To provide clinicians with sufficient information for selecting optimal access strategies for patients with end-stage renal disease, the utilization of health-care services of patients receiving arteriovenous fistulas (AVFs), arteriovenous grafts (AVGs), and central venous catheters (CVCs) are crucial topics that require investigation. MATERIALS AND METHODS: This study involved 1248, 431, and 323 patients with end-stage renal disease who had received an AVF, AVG, or CVC, respectively. All sampled patients were monitored over the course of a 1-y study period to evaluate their medical utilization. The utilization were further categorized into nephrology and nonnephrology services. This study also performed univariate and multivariate regressions to estimate the effects of vascular accesses. RESULTS: Regarding the utilization of health care services, significant differences were observed for mean outpatient visits (45.30 versus 49.71 versus 48.80), outpatient costs (US$19117 versus US$21015 versus US$19280), inpatient days (9.77 versus 14.41 versus 21.60), inpatient costs (US$2627 versus US$3810 versus US$5238), and total costs (US$21743 versus US$24825 versus US$24518) among patients who had received an AVF, AVG, or CVC, respectively. Furthermore, patients receiving an AVF had lower total costs for all health care services and nonnephrology services than patients undergoing AVG or CVC across the categories of men, women, adults, and elderly individuals. Multiple regressions found that patients undergoing AVF had significantly lower total costs for all health services than patients undergoing other vascular accesses after adjustments. CONCLUSIONS: This study displayed that patients who received an AVF fully used health care and nonnephrology services than patients who received an AVG or CVC.

Platelet MicroRNA 365-3p Expression Correlates with High On-treatment Platelet Reactivity in Coronary Artery Disease Patients.

PURPOSE: The expression level of platelet microRNAs (miRNAs) correlates with heart disease and may be altered by antiplatelet therapy. This study aims to assess whether certain miRNAs are associated with treatment response by platelets in patients who received percutaneous coronary intervention and antiplatelet therapy. The dynamic expression of certain miRNAs in patients receiving different antiplatelet regimens was also investigated. METHODS: Healthy subjects (N = 20) received no-stent or antiplatelet therapy (as control), and patients (N = 155) who underwent stent implant and received treatment regimens that included aspirin plus clopidogrel, ticagrelor, or cilostazol were included. The association of miR-96-5p, miR-495-3p, miR-107, miR-223-3p, miR-15a-5, miR-365-3p, and miR-339-3p levels with treatment response, SYNTAX score, and HTPR was determined. RESULTS: Of the different treatment regimens, ticagrelor was the most efficacious. At 24 h following drug administration, ROC analysis revealed that miR-339-3p and miR-365-3p had the highest sensitivity (74.3% and 90.0%, respectively) and specificity (71.4% and 93.3%) for detecting HTPR compared with the five other miRNAs. The SYNTAX score positively correlated with miR-223-3p and miR-365-3p levels at 24 h (P ≤ 0.006) and with miR-365-3p levels 7 days following drug administration (P = 0.014). The expression of all three miRNAs reached the highest levels in hyperresponsive (P2Y12 reaction unit < 85) followed by hyporesponsive (P2Y12 reaction unit ≥ 208) and then normoreactive. The normoreactive value was very close to that of controls. CONCLUSIONS: Our data suggest that miR-365-3p expression level correlates with the antiplatelet treatment response. CLINICAL TRIAL REGISTRATION: NCT02101437.

Successful Thoracic Endovascular Aortic Repair in Ortner's Syndrome.

We present the case of an 89-year-old man with 3-month history of hoarseness and no other significant clinical manifestations. Flexible laryngoscopy revealed a paralyzed left vocal cord, and contrast-enhanced computed tomography showed a thoracic dissecting aortic aneurysm of the distal aortic arch and proximal descending aorta. The aortic aneurysm was repaired through implantation of an endovascular stent graft, and the patient was discharged uneventfully after a week. The false lumen was completely thrombosed, and the patient had a partial resolution of hoarseness at the 1-year follow-up.

The implication of seniority of supervising attending surgeon on the reexploration rate following elective coronary artery bypass grafting.

BACKGROUND AND AIMS: During coronary artery bypass graft (CABG) surgery, the residual hemostasis procedures, from weaning cardiopulmonary bypass to closing sternotomy, are always completed by residents and supervised by attending surgeons. We want to evaluate the teaching effectiveness for residents under the supervision of attending surgeons with different levels of seniority. MATERIALS AND METHODS: Between January 1st 2001 and December 31st 2010, 2279 consecutive CABG surgeries were performed in our medical center. In total, 83 patients underwent a reexploration for postoperative bleeding. All causes of bleeding were identified and recorded. Competent attending surgeons were defined as having >3 years' experience and young attending surgeons with ≦3 years' experience. We compared the reexploration rate and aimed to identify the common sources of bleeding by the two groups. We also assessed the impact of attending experience on the outcomes and major complications after reexploration. RESULTS: There were 36 surgical bleeding and 17 non-surgical bleeding in the young group and 16 surgical bleeding and 14 non-surgical bleeding in the competent group. The young group experienced more mediastinal drainage before a reexploration and a longer time interval to a reexploration. However, both are without statistical significance. Furthermore, the young group has a significant longer hospital stay. The most common intra-pericardium surgical bleeding included two-stage cannulation, side branch of the left internal mammary artery (LIMA), and side branch of vein grafts. The most common extra-pericardium surgical bleeding included a puncture hole by sternal wires, LIMA bed, and fragile sternum. CONCLUSION: Young attending surgeons indeed had both higher incidence of reexploration and surgical bleeding after a CABG. However, the supervisor experience only impacted hospital stay, not major complications or mortality after a reexploration. This might imply the competent attending surgeons provide higher teaching effectiveness for the hemostasis procedure after CABG.

Tanshinone IIA Inhibits High Glucose-Induced Collagen Synthesis via Nuclear Factor Erythroid 2-Related Factor 2 in Cardiac Fibroblasts.

BACKGROUND/AIMS: Diabetes is associated with increased incidence of myocardial dysfunction, which is partly characterized by interstitial and perivascular fibrosis. Cardiac fibroblasts have been identified as an important participant in the development of cardiac fibrosis. Exposure of cultured cardiac fibroblasts to high glucose resulted in increased collagen synthesis. Tanshinone IIA can alleviate the ventricular fibrosis that develops in a number of different experimental conditions. However, whether tanshinone IIA can prevent high glucose-induced collagen synthesis in cardiac fibroblasts remains unknown. The aim of this study was to evaluate the effects of tanshinone IIA on high glucose-induced collagen synthesis in cardiac fibroblasts. METHODS: Rat cardiac fibroblasts were cultured in high glucose (25 mM) media in the absence or presence of tanshinone IIA and the changes in collagen synthesis, transforming growth factor-ß1 (TGF-ß1) production and related signaling molecules were assessed by 3H-proline incorporation, quantitative polymerase chain reaction, enzyme linked immunosorbent assay, and Western blotting. RESULTS: The results indicate cardiac fibroblasts exposed to high glucose condition show increased cell proliferation and collagen synthesis and these effects were abolished by tanshinone IIA treatment. Furthermore, the inhibitory effect of tanshinone IIA on high glucose induced cell proliferation and collagen synthesis may be associated with its activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the inhibition of TGF-ß1 production and Smad2/3 phosphorylation. CONCLUSION: In summary, our results highlights the critical role tanshinone IIA plays as an antioxidant in attenuating high glucose-mediated collagen synthesis through inhibiting TGF-ß1/Smad signaling in cardiac fibroblasts which provide a mechanistic basis for the clinical application of tanshinone IIA in the treating diabetic-related cardiac fibrosis.

Identifying the Risk Factor and Prevention of Limb Ischemia in Extracorporeal Membrane Oxygenation with Femoral Artery Cannulation.

OBJECTIVE: Application of extracorporeal membrane oxygenation (ECMO) for life support has been widely used in various fields of resuscitation. When the common femoral artery (CFA) is used during cannulation for ECMO support in adults, it is often complicated by limb ischemia. Placement of distal perfusion catheter (DPC) can reduce the incidence of limb ischemia and increases the likelihood of limb preservation, but selection criteria is uncertain. METHODS: This is a retrospective study. Data was reviewed for patients in one medical center who were supported by venoarterial extracorporeal membrane oxygenation (VA-ECMO) via CFA cannulation percutaneously between January 2008 and June 2014. Two groups were divided into no-ischemia and ischemic limb. Age, sex, height, weight, body surface area (BSA), cannula size, femoral artery diameter, comorbidity, acute physiology and chronic health evaluation (APACHE) II score, vasoactive-inotropic score (VIS) and mortality rate were analyzed. Doppler was used by measuring the distal pulsation in the dorsalis pedis and posterior tibial artery to select the patients. A DPC was prophylactically inserted percutaneously into the superficial femoral artery for antegrade flow to the extremity in the patients who met selection criteria. RESULTS: 139 (43.6%) patients were included in the study and limb ischemia occurred in 46 (33%) of 139. There was a significant difference between the no-ischemia group and the ischemia group in age (55.5 ± 14.2 versus 63.2 ± 13.2; P < .001), common femoral artery diameter (0.82 ± 0.14 versus 0.63 ± 0.17; P < .001 ), known peripheral artery occlusive disease (9% versus 24%; P < .001) and VIS (12.1 ± 8.1 versus 15.8 ± 10.1; P < .001). Mortality rate was higher in the ischemia group (46% versus 26% ; P < .001). 11 patients who met the selection criteria had a DPC prophylactically inserted and no ischemia limb occurred. CONCLUSION: Smaller common femoral artery diameter (≤6.3 cm); known peripheral arterial occlusive disease; higher VIS (≥15.8); absence of distal pulsation pre-cannulation or immediately after post-cannulation or 4 hrs later have higher risk of limb ischemia when CFA cannulation is used for VA-ECMO. Due to this, the mortality and morbidity rate increases when limb ischemia occurs. A DPC should be prophylactically inserted in high-risk patients who meet selection criteria.

A Rare Experience of Infective Residual Sheath in the Wall of the Innominate Vein after Extraction of Implantable-Defibrillators.

BACKGROUND: Cardiac device-related infective endocarditis is an uncommon but potentially fatal complication. Therefore, cardiac devices should be removed as soon as a device-related infection is suspected. CASE REPORT: A 56-year-old male with a history of arrhythmogenic right ventricular dysplasia with implantable cardioverter-defibrillators (ICDs) 7 years earlier and re-implantation of ICDs due to dysfunction 18 months ago presented with erosion of the ICD pocket with Pseudomonas bacteremia. For the past year, only multiple wound debridements were performed. Accordingly, we performed debridement and removal of the generator during this admission; however, bacteremia still persisted. Using transesophageal echocardiography, we detected vegetation on the pacing leads and tricuspid valve in the right atrium. We performed thoracotomy with tricuspid valve repair and pacing wire removal. However, anterior chest pain and refractory bacteremia occurred 3 months later after discharge, and an infectious foreign body in the wall of the innominate vein was detected using chest computer tomography. Thoracotomy was again performed for resection of the innominate vein with the infection source. Postoperative recovery was good, with no systemic infection or bacteremia. CONCLUSIONS: Pacing lead extraction is a common procedure following cardiac rhythm management device-related infection. However, residual foreign body-related bacteremia should be suspected in cases with fever of unknown origin after primary surgery. Preserving the innominate vein with patch repair is a feasible option. However, a postoperative 4-week course of antibiotics is recommended.

Multimedia Exercise Training Program Improves Distance Walked, Heart Rate Recovery, and Self-efficacy in Cardiac Surgery Patients.

BACKGROUND: Patient education has been shown to be more effective when delivered using multimedia than written materials. However, the effects of using multimedia to assist patients in cardiac rehabilitation have not been investigated. OBJECTIVE: The purpose of this study is to examine the effect of an inpatient multimedia exercise training program on distance walked in the 6-minute walking test (6MWT), heart rate recovery, and walking self-efficacy of patients who had undergone heart surgery. METHODS: For this longitudinal quasi-experimental study, 60 consecutive patients were assigned to an experimental (n = 20; inpatient multimedia exercise training program) or control (n = 40; routine care) group. Data were collected at 3 times (before surgery, 1 to 2 days before hospital discharge, and 1 month after hospital discharge) and analyzed with the generalized estimating equation approach. RESULTS: Most subjects were men (66.7%), had a mean age of 61.32 ± 13.4 years and left ventricular ejection fraction of 56.96% ± 13.28%, and underwent coronary artery bypass graft surgery (n = 34, 56.7%). Subjects receiving the exercise training program showed significantly greater improvement than those in the control group in the 6MWT walking distance (P < .001), heart rate recovery (P = .04), and self-efficacy (P = .002) at hospital discharge. Furthermore, the intervention effects on 6MWT distance (P < .001) and self-efficacy (P < .001) were sustained at 1 month after hospital discharge. CONCLUSION: Our inpatient multimedia exercise training program safely improved distance walked in the 6MWT, heart rate recovery, and self-efficacy at hospital discharge in patients after heart surgery and maintained their improvement in 6MWT and self-efficacy 1 month later.

TLR4-Activated MAPK-IL-6 Axis Regulates Vascular Smooth Muscle Cell Function.

Migration of vascular smooth muscle cells (VSMCs) into the intima is considered to be a vital event in the pathophysiology of atherosclerosis. Despite substantial evidence supporting the pathogenic role of Toll-like receptor 4 (TLR4) in the progression of atherogenesis, its function in the regulation of VSMC migration remains unclear. The goal of the present study was to elucidate the mechanism by which TLR4 regulates VSMC migration. Inhibitor experiments revealed that TLR4-induced IL-6 secretion and VSMC migration were mediated via the concerted actions of MyD88 and TRIF on the activation of p38 MAPK and ERK1/2 signaling. Neutralizing anti-IL-6 antibodies abrogated TLR4-driven VSMC migration and F-actin polymerization. Blockade of p38 MAPK or ERK1/2 signaling cascade inhibited TLR4 agonist-mediated activation of cAMP response element binding protein (CREB). Moreover, siRNA-mediated suppression of CREB production repressed TLR4-induced IL-6 production and VSMC migration. Rac-1 inhibitor suppressed TLR4-driven VSMC migration but not IL-6 production. Importantly, the serum level of IL-6 and TLR4 endogenous ligand HMGB1 was significantly higher in patients with coronary artery diseases (CAD) than in healthy subjects. Serum HMGB1 level was positively correlated with serum IL-6 level in CAD patients. The expression of both HMGB1 and IL-6 was clearly detected in the atherosclerotic tissue of the CAD patients. Additionally, there was a positive association between p-CREB and HMGB1 in mouse atherosclerotic tissue. Based on our findings, we concluded that, upon ligand binding, TLR4 activates p38 MAPK and ERK1/2 signaling through MyD88 and TRIF in VSMCs. These signaling pathways subsequently coordinate an additive augmentation of CREB-driven IL-6 production, which in turn triggers Rac-1-mediated actin cytoskeleton to promote VSMC migration.