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OBJECTIVE: This study aimed to delineate the recovery patterns of regional oxygen saturation (SrO2) in pediatric cardiac surgery patients subjected to remote ischemic preconditioning (RIPC), utilizing near-infrared spectroscopy (NIRS) for quantification. It also sought to establish the correlation between these perfusion patterns and postoperative clinical outcomes. DESIGN: A prospective longitudinal observational study. SETTING: The study was conducted at Fundación Valle Del Lili, a high-complexity service provider institution in Fundación Valle Del Lili. PARTICIPANTS: Pediatric patients (younger than 18 years of age) scheduled for elective cardiac surgery requiring cardiopulmonary bypass between August 2022 and July 2023. INTERVENTIONS: RIPC was performed after anesthetic induction, involving cycles of ischemia and reperfusion on a lower limb. Monitoring included SrO2 using NIRS. MEASUREMENTS AND MAIN RESULTS: The study identified 4 distinct patterns of SrO2 during RIPC. Findings demonstrated a significant association between the negative SrO2 pattern and increased postoperative adverse events, including extended hospital stays and higher mortality, while a positive pattern was associated with better outcomes. CONCLUSIONS: Specific patterns of SrO2 response to RIPC may serve as important indicators for risk stratification in congenital heart surgery. This study illustrated the potential of NIRS in detecting hypoxic states and predicting postoperative outcomes, emphasizing the need for standardized clinical interpretation of RIPC patterns.

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Congenital heart diseases impact millions annually, with pediatric care lacking suitable risk assessment tools. This research seeks to illuminate the association between the global longitudinal strain (GLS) and the subsequent impact on postoperative outcomes, contributing to a deeper understanding of its predictive value in the pediatric population affected by congenital heart diseases. An observational, analytic, longitudinal, and prospective study was conducted from May 2022 to May 2023, including all patients under 18 undergoing heart surgery with cardiopulmonary bypass (CBP). Patients not classifiable within the Risk Adjustment for Congenital Heart Surgery were excluded. Using transesophageal echocardiography, GLS was measured pre- and post-CPB. Receiver operating characteristic curve analysis determined GLS cut-off points for 30-day mortality risk, using Youden's method for optimal sensitivity and specificity. Bivariate and multivariate analysis identified the relationships between clinical variables. Eighty-nine patients undergoing congenital heart surgery were included. Fifteen deaths occurred. The area under the curve (AUC) for each GLS classification (pre, post, index) demonstrated effective discriminatory capacity (> 0.70) in predicting 30-day mortality. Pre-CBP GLS showed the strongest predictive power (AUC 0.833, IQR: 0.731 - 0.936) with a cut-off point of 12. Values lower than the cut-off point of pre-CPB GLS correlated with increased vasoactive-inotropic Scores and longer mechanical ventilation. GLS measurement is a reproducible method for assessing ventricular function in pediatric heart surgery, showing potential as a prognostic tool. This study marks the initial effort to establish cut-off points for preoperative GLS, postoperative GLS, and the strain index.

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The modification of the rutile TiO2(110) surface with dopamine represents the best example of the functionalization of TiO2-based nanoparticles with catecholamines, which is of great interest for sunlight harvesting and drug delivery. However, there is little information on the dopamine-TiO2(110) adsorption complex in terms of thermodynamic properties and structural parameters such as bond coordination and orientation of the terminal ethyl-amino group. Here, we report a density functional theory (DFT) investigation of dopamine adsorption on the TiO2(110) surface using the optB86b-vdW functional with a Hubbard-type correction to the Ti 3d orbitals, where U eff = 3 eV. Guided by available X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) data, our simulations identify enolate species with bidentate coordination at a submonolayer coverage, which are bonded to two neighboring 5-fold-coordinated Ti atoms at the TiO2(110) surface through both deprotonated oxygen atoms of the dopamine, i.e., in a bridging fashion. The process is highly exothermic, involving an adsorption energy of -2.90 eV. Calculated structural parameters suggest that the molecule sits approximately upright on the surface with the amino group interacting with the π-like orbitals of the aromatic ring, leading to a gauche-like configuration. The resulting NH···π hydrogen bond in this configuration can be broken by overcoming an energy barrier of 0.22 eV; in this way, the amino group rotation leads to an anti-like conformation, making this terminal group able to bind to other biomolecules. This mechanism is endothermic by 0.07 eV. Comparison of existing spectroscopic data with DFT modeling shows that our computational setup can reproduce most experimentally determined parameters such as tilt angles from NEXAFS and chemical shifts in XPS, which allows us to identify the preferred mode of adsorption of dopamine on the TiO2(110) surface.

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Human α1D-adrenoceptors are G protein-coupled receptors that mediate adrenaline/noradrenaline actions. There is a growing interest in identifying regulatory domains in these receptors and determining how they function. In this work, we show that the absence of the human α1D-adrenoceptor carboxyl tail results in altered ERK (extracellular signal-regulated kinase) and p38 phosphorylation states. Amino terminus-truncated and both amino and carboxyl termini-truncated α1D-adrenoceptors were transfected into Rat-1, HEK293, and B103 cells, and changes in the phosphorylation state of extracellular signal-regulated kinase was assessed using biochemical and biophysical approaches. The phosphorylation state of other protein kinases (p38, MEK1, and Raf-1) was also studied. Noradrenaline-induced ERK phosphorylation in Rat-1 fibroblasts expressing amino termini-truncated α1D-adrenoceptors. However, in cells expressing receptors with both amino and carboxyl termini truncations, noradrenaline-induced activation was abrogated. Interestingly, ERK phosphorylation that normally occurs through activation of endogenous G protein-coupled receptors, EGF receptors, and protein kinase C, was also decreased, suggesting that downstream steps in the mitogen-activated protein kinase pathway were affected. A similar effect was observed in B103 cells but not in HEK 293 cells. Phosphorylation of Raf-1 and MEK1 was also diminished in Rat-1 fibroblasts expressing amino- and carboxyl-truncated α1D-adrenoceptors. Our data indicate that expression of carboxyl terminus-truncated α1D-adrenoceptors alters ERK and p38 phosphorylation state.

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Sphingosine-1-phosphate-induced α1B-adrenergic receptor desensitization and phosphorylation were studied in rat-1 fibroblasts stably expressing enhanced green fluorescent protein-tagged adrenoceptors. Sphingosine-1-phosphate induced adrenoceptor desensitization and phosphorylation through a signaling cascade that involved phosphoinositide 3-kinase and protein kinase C activities. The autocrine/paracrine role of sphingosine-1-phosphate was also studied. It was observed that activation of receptor tyrosine kinases, such as insulin growth factor-1 (IGF-I) and epidermal growth factor (EGF) receptors increased sphingosine kinase activity. Such activation and consequent production of sphingosine-1-phosphate appear to be functionally relevant in IGF-I- and EGF-induced α1B-adrenoceptor phosphorylation and desensitization as evidenced by the following facts: a) expression of a catalytically inactive (dominant-negative) mutant of sphingosine kinase 1 or b) S1P1 receptor knockdown markedly reduced this growth factor action. This action of sphingosine-1-phosphate involves EGF receptor transactivation. In addition, taking advantage of the presence of the eGFP tag in the receptor construction, we showed that S1P was capable of inducing α1B-adrenergic receptor internalization and that its autocrine/paracrine generation was relevant for internalization induced by IGF-I. Four distinct hormone receptors and two autocrine/paracrine mediators participate in IGF-I receptor-α1B-adrenergic receptor crosstalk.

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