TBX3 transfection and nodal signal pathway inhibition promote differentiation of adipose mesenchymal stem cell to cardiac pacemaker-like cells.

BACKGROUND: Mesenchymal stem cells (MSCs) are known as one of the best candidate cells to produce cardiac pacemaker-like cells (CPLCs). Upregulation of TBX3 transcription factor and inhibition of the nodal signal pathway have a significant role in the formation of cardiac pacemaker cells such as sinoatrial and atrioventricular nodes, which initiate the heartbeat and control the rhythm of heart contractions. This study aimed to confirm the effects of transfection of TBX3 transcription factor and inhibition of the nodal signal pathway on differentiating adipose-derived MSCs (AD-MSCs) to CPLCs. AD-MSCs were characterized using flow cytometry and three-lineage differentiation staining. METHODS: The transfection of TBX3 plasmid was carried out using lipofectamine, and inhibition of the nodal signal pathway was done using the small-molecule SB431542. The morphology of the cells was observed using a light microscope. Pacemaker-specific markers, including TBX3, Cx30, HCN4, HCN1, HCN3, and KCNN4, were evaluated using the qRT-PCR method. For protein level, TBX3 and Cx30 were evaluated using ELISA and immunofluorescence staining. The electrophysiology of cells was evaluated using a patch clamp. RESULTS: The TBX3 expression in the TBX3, SM, and TBX + SM groups significantly higher (p < 0.05) compared to the control group and cardiomyocytes. The expression of Cx40 and Cx43 genes were lower in TBX3, SM, TBX + SM groups. In contrast, Cx30 gene showed higher expression in TBX3 group. The expression HCN1, HCN3, and HCN4 genes are higher in TBX3 group. CONCLUSION: The transfection of TBX3 and inhibition of the nodal signal pathway by small-molecule SB431542 enhanced differentiation of AD-MSCs to CPLCs.

Intraoperative Goal-Directed Perfusion in Cardiac Surgery with Cardiopulmonary Bypass: The Roles of Delivery Oxygen Index and Cardiac Index.

PURPOSE: Goal-directed perfusion (GDP) refers to individualized goal-directed therapy using comprehensive monitoring and optimizing the delivery of oxygen during cardiopulmonary bypass (CPB). This study aims to determine whether the intraoperative GDP protocol method has better outcomes compared to conventional methods. METHODS: We searched the PubMed, Central, and Scopus databases up to October 12, 2023. We primarily examined the GDP protocol in adult cardiac surgery, using CPB with oxygen delivery index (DO2I) and cardiac index (CI) as the main parameters. RESULTS: In all, 1128 participants from seven studies were included in our analysis. The results showed significant differences in the duration of intensive care unit (ICU) stays (p = 0.01), with a mean difference of -0.33 (-0.59 to 0.07), and hospital length of stay (LOS) (p = 0.0002), with a mean difference of -0.84 (-1.29 to -0.39). There was also a notable reduction in postoperative complications (p <0.00001), odds ratio (OR) of 0.43 (0.32-0.60). However, there was no significant decrease in mortality rate (p = 0.54), OR of 0.77 (0.34-1.77). CONCLUSION: Postoperative acute kidney injury and ICU and hospital LOS are significantly reduced when GDP protocols with indicators of flow management, oxygen delivery index, and CI are used in intraoperative cardiac surgery using CPB.

Validation for EuroSCORE II in the Indonesian cardiac surgical population: a retrospective, multicenter study.

BACKGROUND: In 2011, the European System for Cardiac Operative Risk (EuroSCORE) II was created as an improvement of the additive/logistic EuroSCORE for the prediction of mortality after cardiac surgery. OBJECTIVE: To validate EuroSCORE II in predicting the mortality of open cardiac surgery patients in Indonesia. METHODS: We performed a multi-center retrospective study of cardiac surgery patients from three participating centers (Dr. Sardjito Hospital, Kariadi Hospital, and Abdul Wahab Sjahranie Hospital) between January 1st, 2016, and December 31st, 2020. Discrimination and calibration tests were performed. RESULTS: The observed mortality rate was 9.5% (73 out of 767 patients). The median EuroSCORE II value was 1.13%. The area under the curve for EuroSCORE II was 0.71 (95% CI: 0.65-0.77), suggesting fair discriminatory power. Calibration analysis suggested that EuroSCORE II underestimated postoperative mortality. Gender, age, chronic pulmonary disease, limited mobility, NYHA, and critical pre-operative state were significant predictors of post-cardiac surgery mortality in our population. CONCLUSION: This study suggested that the EuroSCORE II was a poor predictor for postoperative mortality in Indonesian patients who underwent cardiac surgery procedures. Therefore, EuroSCORE II may not be suitable for mortality risk prediction in Indonesian populations, and surgical planning should be decided on an individual basis.

The Effect of Low Preoperative Ejection Fraction on Mortality After Cardiac Surgery in Indonesia.

Background: Among cardiac surgery patients, low preoperative left ventricular ejection fraction (LVEF) is common and has been associated with poor outcomes. The objective of this study was to assess the association between LVEF and postoperative mortality in patients undergoing open-heart surgery in several hospitals in Indonesia. Methods: We conducted a multicenter study with the retrospective design using data from patients undergoing open-heart surgery in 4 institutions in Indonesia. Data regarding LVEF and other potential risk factors were extracted from medical records and compiled in one datasheet. Statistical analyses were performed to assess if low LVEF was associated with postoperative mortality and identify other potential risk factors. Results: A total of 4789 patients underwent cardiac surgery in participating centers during the study period. Of these, 189 subjects (3.9%) had poor preoperative LVEF. Poor LVEF was associated with postoperative mortality (adjusted OR 2.761, 95% CI 1.763-4.323, p < 0.001). Based on types of surgery, LVEF had a significant association with mortality only in CABG patients, while there was no such association in valve surgery and inconclusive in congenital surgery patients. Other significant independent predictors of in-hospital mortality included age more than 65 years old, non-elective surgery, the complexity of procedures, history of cardiac surgery, organ failure, CARE score ≥ 3, NYHA class ≥ III, and poor right ventricular function. Conclusion: Patients with low preoperative LVEF undergoing open-heart surgery had a higher risk of postoperative mortality. Cardiac surgery can be performed with acceptable mortality rates. Accurate selection of patients, risk/benefit evaluation, and planning of surgical and anesthesiological management are mandatory to improve outcomes.

The Role of MicroRNA in Contrast-Induced Nephropathy: A Scoping Review and Meta-Analysis.

OBJECTIVE: Early diagnosis of contrast-induced nephropathy (CIN) remains crucial for successful treatment; unfortunately, the widely used serum creatinine is elevated only in the late stage of CIN. The circulating microRNAs (miRNAs) are stable biomarker that might be useful. The aim of this scoping review and meta-analysis is to assess the role of miRNAs in CIN. METHODS: We performed a systematic literature search on topics that assess the role of miRNAs in CIN from several electronic databases. RESULTS: There were 6 preclinical studies and 2 of them validated their findings in human. Only miR-30a, miR-30c, miR-30e, and miR-188 have been validated in human models. Meta-analysis showed that increase in miR-30a expression was associated with higher incidence of CIN (OR 4.48 [1.52, 13.26], p = 0.007; I 2: 94%, p < 0.001). An increase in miR-30e expression was associated with higher incidence of CIN (OR 2.34 [1.70, 3.20], p < 0.001; I 2: 0%, p = 0.76). There is an indication that miR-188 is associated with contrast-induced apoptosis and might potentially be a drug target in the future. CONCLUSION: This study highlighted the importance of certain miRNAs in CIN pathophysiology. Future researches should explore on the prognostic and therapeutic implication of miRNA in CIN.