RESUMEN
Myocardial infarction (MI) is a fatal heart disease that affects millions of lives worldwide each year. This study investigated the roles of HIF-1α/lncRNA-TUG1 in mitochondrial dysfunction and pyroptosis in MI. CCK-8, DHE, lactate dehydrogenase (LDH) assays, and JC-1 staining were performed to measure proliferation, reactive oxygen species (ROS), LDH leakage, and mitochondrial damage in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Enzyme-linked immunoassay (ELISA) and flow cytometry were used to detect LDH, creatine kinase (CK), and its isoenzyme (CK-MB) levels and caspase-1 activity. Chromatin immunoprecipitation (ChIP), luciferase assay, and RNA-immunoprecipitation (RIP) were used to assess the interaction between HIF-1α, TUG1, and FUS. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to measure HIF-1α, TUG1 and pyroptosis-related molecules. Hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC), and terminal deoxynucleotidyl transferase dUTP risk end labelling (TUNEL) staining were employed to examine the morphology, infarction area, and myocardial injury in the MI mouse model. Mitochondrial dysfunction and pyroptosis were induced in H/R-treated cardiomyocytes, accompanied by an increase in the expression of HIF-α and TUG1. HIF-1α promoted TUG1 expression by directly binding to the TUG1 promoter. TUG1 silencing inhibited H/R-induced ROS production, mitochondrial injury and the expression of the pyroptosis-related proteins NLRP3, caspase-1 and GSDMD. Additionally, H/R elevated FUS levels in cardiomyocytes, which were directly inhibited by TUG1 silencing. Fused in sarcoma (FUS) overexpression reversed the effect of TUG1 silencing on mitochondrial damage and caspase-1 activation. However, the ROS inhibitor N-acetylcysteine (NAC) promoted the protective effect of TUG1 knockdown on H/R-induced cardiomyocyte damage. The in vivo MI model showed increased infarction, myocardial injury, ROS levels and pyroptosis, which were inhibited by TUG1 silencing. HIF-1α targeting upregulated TUG1 promotes mitochondrial damage and cardiomyocyte pyroptosis by combining with FUS, thereby promoting the occurrence of MI. HIF-1α/TUG1/FUS may serve as a potential treatment target for MI.
RESUMEN
BACKGROUND: Inhalational anesthesia with sevoflurane for endotracheal intubation without muscle relaxant is now used widely for pediatric patients. This study assessed the efficacy and safety of induction with high concentration sevoflurane and of nasotracheal intubation without muscle relaxant in infants with increased or decreased pulmonary blood flow (PBF) and undergoing surgery for congenital heart diseases. METHODS: Fifty-five infants aged 2 - 12 months, weighing 4.7 - 10.0 kg, and scheduled for congenital cardiac surgery were enrolled. Subjects were divided into those with increased (IPBF group, n = 29) and decreased (DPBF group, n = 26) pulmonary blood flow. All infants received inhalational induction with 8% sevoflurane in 100.0% oxygen at a gas flow rate of 6 L/min. Nasotracheal intubation was performed 4 minutes after induction. Sevoflurane vaporization was decreased to 4.0% for placement of a peripheral intravenous line and invasive hemodynamic monitors. Five minutes later, sedatives and muscle relaxant were administered and the vaporizer was adjusted to 2% for maintenance of anesthesia. Bispectral index (BIS) scores, circulatory parameters, satisfactory and successful intubation ratios, adverse reactions, and complications of intubation were recorded. RESULTS: Times to loss of lash and pain reflexes were longer for the DPBF group (P < 0.01). Satisfactory intubation ratios were 93.1% and 61.5% for the IPBF and DPBF groups, respectively (P = 0.008). Successful intubation ratios were 96.6% and 76.9% for the IPBF and DPBF groups, respectively (P = 0.044). Following sevoflurane inhalation, blood pressures decreased significantly in the IPBF group but remained stable in the DPBF group. BIS scores declined to similar stable values, and a "nadir BIS" was recorded for both groups. No obvious adverse reactions or complications of intubation were noted perioperatively. CONCLUSIONS: Induction with high concentration sevoflurane, although faster for infants with IPBF, is safe for infants with IPBF or DPBF. However, nasotracheal intubation without muscle relaxant after induction with high concentration sevoflurane is less successful and less satisfactory for infants with DPBF and should be used with caution in this patient group.