Exploring the Impact of BKCa Channel Function in Cellular Membranes on Cardiac Electrical Activity.

This review paper delves into the current body of evidence, offering a thorough analysis of the impact of large-conductance Ca2+-activated K+ (BKCa or BK) channels on the electrical dynamics of the heart. Alterations in the activity of BKCa channels, responsible for the generation of the overall magnitude of Ca2+-activated K+ current at the whole-cell level, occur through allosteric mechanisms. The collaborative interplay between membrane depolarization and heightened intracellular Ca2+ ion concentrations collectively contribute to the activation of BKCa channels. Although fully developed mammalian cardiac cells do not exhibit functional expression of these ion channels, evidence suggests their presence in cardiac fibroblasts that surround and potentially establish close connections with neighboring cardiac cells. When cardiac cells form close associations with fibroblasts, the high single-ion conductance of these channels, approximately ranging from 150 to 250 pS, can result in the random depolarization of the adjacent cardiac cell membranes. While cardiac fibroblasts are typically electrically non-excitable, their prevalence within heart tissue increases, particularly in the context of aging myocardial infarction or atrial fibrillation. This augmented presence of BKCa channels' conductance holds the potential to amplify the excitability of cardiac cell membranes through effective electrical coupling between fibroblasts and cardiomyocytes. In this scenario, this heightened excitability may contribute to the onset of cardiac arrhythmias. Moreover, it is worth noting that the substances influencing the activity of these BKCa channels might influence cardiac electrical activity as well. Taken together, the BKCa channel activity residing in cardiac fibroblasts may contribute to cardiac electrical function occurring in vivo.

The Impact of Complete Revascularization in Symptomatic Severe Left Ventricular Dysfunction between Coronary Artery Bypass Graft and Percutaneous Coronary Intervention.

Objective: The study aimed to compare the clinical outcomes between the patients receiving coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) for the patients with symptomatic severe left ventricular (LV) dysfunction and coronary artery disease (CAD). Methods: Between February 2007 and February 2020, a total of 745 patients who received coronary artery angiography for reduced LV ejection fraction (LVEF) < 40% and symptomatic New York Heart Association (NYHA) functional class ≥ 3 were recruited. The patients (N = 236) who were diagnosed with dilated cardiomyopathy or valvular heart disease without coronary artery stenosis, those with prior history of CABG or valvular surgery (N = 59), those who presented ST-segment elevated myocardial infarction (STEMI), those with a CAD and SYNTAX score of ≦ 22 (N = 175), those who received emergent CABG for coronary perforation (N = 3), and those who had NYHA class ≦ 2 (N = 65) were excluded. Finally, 116 patients with reduced LVEF and those who had a SYNTAX score >22, who received CABG (N = 47) and PCI (N = 69), were recruited for this study. Results: There was no significant difference in the incidence values of in-hospital course and those of in-hospital mortality, acute kidney injury, and postprocedural hemodialysis. There was no significant difference in the 1-yearfollow-up of recurrent MI, revascularization, or stroke between the groups. The 1-year heart failure (HF) hospitalization rate was significantly lower in the CABG group than in all patients of the PCI group (13.2% vs. 33.3%; p = 0.035); however, there was no significant difference in the same variable between the CABG group and the complete revascularization subgroup (13.2% vs. 28.2%; p = 0.160). The revascularization index (RI) was significantly higher in the CABG group than in all patients of the PCI group or complete revascularization subgroup (0.93 ± 0.12 vs. 0.71 ± 0.25; p < 0.001) and (0.93 ± 0.12 vs. 0.86 ± 0.13; p = 0.019). The 3-year HF hospitalization rate was significantly lower in the CABG group than in all patients of the PCI group (16.2% vs. 42.2%; p = 0.008); however, there was no difference in the same variable between the CABG group and the complete revascularization subgroup (16.2% vs. 35.1%; p = 0.109). Conclusions: In patients with symptomatic (NYHA class ≥ 3) severe LV dysfunction and CAD, CABG brought less HF admission when compared to patients in the PCI group, but this did not differ when compared to the complete revascularization subgroup. Therefore, an extensive revascularization, achieved by CABG or PCI, is associated with a lower HF hospitalization rate during the 3-yearfollow-up period in such populations.

Efficacy and Safety of Veno-Arterial Extracorporeal Membrane Oxygenation in the Treatment of High-Risk Pulmonary Embolism: A Retrospective Cohort Study.

Objectives: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly used to treat high-risk pulmonary embolism (PE). However, its efficacy and safety remain uncertain. This retrospective cohort study aimed to determine whether ECMO could improve the clinical outcomes of patients with high-risk PE. Methods: Forty patients with high-risk PE, who were admitted to Kaohsiung Chang Gung Memorial Hospital between January 2012 and December 2019, were included in this study. Demographic data and clinical outcomes were compared between patients treated without ECMO (non-ECMO group) and those treated with ECMO (ECMO group). Appropriate statistical tools were used to compare variables between groups and the survival was analyzed using the Kaplan-Meier method. Results: The overall in-hospital mortality rate was 55%, in which 65% (26/40) of patients presented with cardiac arrest with a mortality rate of 77%, which was higher than that of patients without cardiac arrest (14%). There was no significant difference in major complications and in-hospital mortality between the non-ECMO and ECMO groups. However, in subgroup analysis, compared with patients treated without ECMO, earlier ECMO treatment was associated with a reduced risk of cardiac arrest (P = 0.023) and lower in-hospital mortality (P = 0.036). A log-rank test showed a significantly higher cumulative overall survival in the earlier ECMO treatment group (P = 0.033). Conclusions: In this retrospective cohort study, earlier ECMO treatment was associated with lower in-hospital mortality among unstable patients without cardiac arrest. Our findings suggest that ECMO can be considered as an initial treatment option for patients with high-risk PE in higher-volume hospitals.

Clinical course and outcome of patients with acute pulmonary embolism rescued by veno-arterial extracorporeal membrane oxygenation: a retrospective review of 21 cases.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being utilized in patients with massive pulmonary embolism (PE). However, the efficacy and the safety remain uncertain. This study aimed to investigate clinical courses and outcomes in ECMO-treated patients with acute PE. METHODS: Twenty-one patients with acute PE rescued by ECMO from January 2012 to December 2019 were retrospectively analysed. Clinical features, laboratory biomarkers, and imaging findings of these patients were reviewed, and the relationship with immediate outcome and clinical course was investigated. RESULTS: Sixteen patients (76.2%) experienced refractory circulatory collapse requiring cardiopulmonary resuscitation (CPR) or ECMO support within 2 h after the onset of cardiogenic shock, and none could receive definitive reperfusion therapy before ECMO initiation. Before or during ECMO support, more than 90% of patients had imaging signs of right ventricular (RV) dysfunction. In normotension patients, the computed tomography (CT) value was a valuable predictor of rapid disease progression compared with cardiac troponin I level. Ultimately, in-hospital death occurred in ten patients (47.6%) and 90% of them died of prolonged CPR-related brain death. Cardiac arrest was a significant predictor of poor prognosis (p = 0.001). CONCLUSIONS: ECMO appears to be a safe and effective circulatory support in patients with massive PE. Close monitoring in intensive care unit is recommended in patients with RV dysfunction and aggressive use of ECMO may reduce the risk of sudden cardiac arrest and improve clinical outcome.

Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34+ Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia.

This study tested whether circulatory endothelial progenitor cells (EPCs) derived from peripheral arterial occlusive disease (PAOD) patients after receiving combined autologous CD34+ cell and hyperbaric oxygen (HBO) therapy (defined as rejuvenated EPCs) would salvage nude mouse limbs against critical limb ischemia (CLI). Adult-male nude mice (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 (CLI-EPCs (6 × 105) derived from PAOD patient's circulatory blood prior to CD34+ cell and HBO treatment (EPCPr-T) by intramuscular injection at 3 h after CLI induction) and group 4 (CLI-EPCs (6 × 105) derived from PAOD patient's circulatory blood after CD34+ cell and HBO treatment (EPCAf-T) by the identical injection method). By 2, 7 and 14 days after the CLI procedure, the ischemic to normal blood flow (INBF) ratio was highest in group 1, lowest in group 2 and significantly lower in group 4 than in group 3 (p < 0.0001). The protein levels of endothelial functional integrity (CD31/von Willebrand factor (vWF)/endothelial nitric-oxide synthase (eNOS)) expressed a similar pattern to that of INBF. In contrast, apoptotic/mitochondrial-damaged (mitochondrial-Bax/caspase-3/PARP/cytosolic-cytochrome-C) biomarkers and fibrosis (Smad3/TGF-ß) exhibited an opposite pattern, whereas the protein expressions of anti-fibrosis (Smad1/5 and BMP-2) and mitochondrial integrity (mitochondrial-cytochrome-C) showed an identical pattern of INBF (all p < 0.0001). The protein expressions of angiogenesis biomarkers (VEGF/SDF-1α/HIF-1α) were progressively increased from groups 1 to 3 (all p < 0.0010). The number of small vessels and endothelial cell surface markers (CD31+/vWF+) in the CLI area displayed an identical pattern of INBF (all p < 0.0001). CLI automatic amputation was higher in group 2 than in other groups (all p < 0.001). In conclusion, EPCs from HBO-C34+ cell therapy significantly restored the blood flow and salvaged the CLI in nude mice.

Shear Bonding Strength and Thermal Cycling Effect of Fluoride Releasable/Rechargeable Orthodontic Adhesive Resins Containing LiAl-F Layered Double Hydroxide (LDH) Filler.

This study aims to investigate the shear bonding strength (SBS) and thermal cycling effect of orthodontic brackets bonded with fluoride release/rechargeable LiAl-F layered double hydroxide (LDH-F) contained dental orthodontic resin. 3% and 5% of LDH-F nanopowder were gently mixed to commercial resin-based adhesives Orthomite LC (LC, LC3, LC5) and Transbond XT (XT, XT3). A fluoroaluminosilicate modified resin adhesive Transbond color change (TC) was selected as a positive control. Fifteen brackets each group were bonded to bovine enamel and the SBS was tested with/without thermal cycling. The adhesive remnant index (ARI) was evaluated at 20× magnification. The fluoride-releasing/rechargeability and cytocompatibility were also evaluated. The SBS of LC, LC3, and LC5 were significantly higher than XT and TC. After thermal cycling, the SBS of LC, LC3, and LC5 did not decrease and was significantly higher than TC. The changes of ARI scores indicate that failure occurred not only cohesive but also semi-cohesive fracture. The 30 days accumulated daily fluoride release of LC3, LC5, and TC without recharge are higher than 300 µg/cm2. The LDH-F contained resin adhesive possesses higher SBS compared to positive control TC. Fluoride release and the rechargeable feature can be achieved for preventing enamel demineralization without cytotoxicity.