Examinando por Autor "Tapia, P."
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Ítem Effect of a lung rest strategy during ECMO in a porcine acute lung injury model(SpringerOpen, 2015-10) Araos, J.; Cruces, P.; Tapia, P.; Alegria, L.; García, P.; Salomon, T.; Rodriguez, F.; Amthauer, M.; Castro, G.; Erranz, B.; Soto, D.; Carreño, P.; Medina, T.; Damiani, F.; Bugedo, G.; Bruhn, A.Introduction ECMO is used to treat patients who develop refractory hypoxemia and to provide a more protective ventilation. Several guidelines recommend “lung rest” strategies based on variable ventilatory parameters. However, there is limited evidence to support this strategy. Objectives To compare the effect of a lung rest strategy based on near-apneic ventilation (Vt 1-2 ml/kg, PEEP 10, respiratory rate-RR 5 min) versus conventional (Vt 10ml/kg, PEEP 5, RR 20/min), and standard protective ventilation (Vt 6ml/kg, PEEP 10, RR 20/min). Methods Twenty-four domestic pigs (26-36 kg) were anesthetized, mechanically ventilated (Vt 10 ml/kg, PEEP 5, O2 1.0) and invasively monitored. Six animals were used as Sham. In the other 18 lung injury was induced by saline lavages (30 ml/kg per lavage) performed repeatedly in both supine and prone position until PaO2/FiO2 dropped below 250. They were then subjected to a 2-hour injurious ventilation with PCV, PEEP = 0, Pinsp = 40 cmH2O, RR = 10/min, I:E = 1:1, one hour in prone and the other in supine. After completing lung injury (time 0) animals were connected to a saline primed-MEDOS Hilite ECMO circuit by inserting a AVALON 23F double-lumen cannula through the external jugular vein. Blood flow was set at 60-70% of cardiac output. Animals were randomized into one of the three groups and ventilated according to randomization for the following 24 hours. Respiratory and hemodynamic data were collected at times 0, 3, 6, 12, 18 and 24h. After euthanizing animals at time 24h, tissue samples were extracted from the lungs and injury evaluated and scored by light microscopy. Total lung water content was estimated by the wet-dry weight ratio. Results PaO2 decreased significantly in all groups after injury, but was progressively restored after ECMO start, despite the study group. Mean arterial pressure remained within normal limits throughout the study period, whereas MPAP increased significantly after injury but reached values close to SHAM soon after ECMO initiation. Lung wet-dry weight ratio and histological injury score increased significantly in all study groups compared to SHAM. Although non-significant, there was a trend towards a better histological injury score when Vt was reduced. Conclusions In this preliminary analysis, we found no clear advantage of reducing Vt when applying ECMO to support a double-hit animal model of ARDS in regard to resolution of lung edema or gas exchange. However, further work is required to determine if the non-significant reduction in lung injury observed in the near-apneic strategy may be relevant in providing further protection to the injured lungs supported by ECMO. © 2015 Araos et al.Ítem Human peritoneal mesothelial cell death induced by high-glucose hypertonic solution involves Ca2+ and Na+ ions and oxidative stress with the participation of PKC/NOX2 and PI3K/Akt pathways(Frontiers Media, 2017-06) Simon, F.; Tapia, P.; Armisen, R.; Echeverria, C.; Gatica, S.; Vallejos, A.; Pacheco, A.; Sanhueza, M.E.; Alvo, M.; Segovia, E.; Torres, R.Chronic peritoneal dialysis (PD) therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH) solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC) death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.Ítem Liquid extracorporeal carbon dioxide removal: use of THAM (tris-hydroxymethyl aminomethane) coupled to hemofiltration to control hypercapnic acidosis in a porcine model of protective mechanical ventilation(E-CENTURY PUBLISHING CORP, 2016) Tapia, P.; Lillo, F; Soto, D; Escobar, L; Simon, F; Hernandez, K; Alegria, L; Bruhn, AA promising approach to facilitate protective mechanical ventilation is the use of extracorporeal CO2 removal techniques. Several strategies based on membrane gas exchangers have been developed. However, these techniques are still poorly available. The goal of this study was to assess the efficacy and safety of THAM infusion coupled to hemofiltration for the management of hypercapnic acidosis. A severe respiratory acidosis was induced in seven anesthetized pigs. Five of them were treated with THAM 8-mmol . kg(-1) . h(-1) coupled to hemofiltration (THAM+HF group) at 100 mL . kg(-1) . h(-1). After 18-hours of treatment the THAM infusion was stopped but hemofiltration was kept on until 24-hours. The 2 other animals were treated with THAM but without hemofiltration. After 1-hour of treatment in THAM+HF, PaCO2 rapidly decreased from a median of 89.0 (IQR) (80.0, 98.0) to 71.3 (65.8, 82.0) mmHg (P<0.05), while pH increased from 7.12 (7.01, 7.15) to 7.29 (7.27, 7.30) (P<0.05). Thereafter PaCO2 remained stable between 60-70 mmHg, while pH increased above 7.4. After stopping THAM at 18 hours of treatment a profound rebound effect was observed with severe hypercapnic acidosis. The most important side effect we observed was hyperosmolality, which reached a maximum of 330 (328, 332) mOsm . kg H2O-1 at T18. The animals treated only with THAM developed severe hypercapnia, despite the fact that pH returned to normal values, and died after 12 hours. Control-group had an uneven evolution until the end of the experiment. A combined treatment with THAM coupled to hemofiltration may be an effective treatment to control severe hypercapnic acidosis.Ítem Procoagulant phenotype induced by oxidized high-density lipoprotein associates with acute kidney injury and death(Elsevier, 2023-03) Prado, Y.; Pérez, L.; Eltit, F.; Echeverría, C.; Llancalahuen, F.; Tapia, P.; González, P.; Kalergis, A.; Cabello-Verrugio, C.Background Oxidative stress derived from severe systemic inflammation promotes conversion from high-density lipoprotein HDL to oxidized HDL (oxHDL), which interacts with vascular endothelial cells (ECs). OxHDL acquires procoagulant features playing a role in modulating coagulation, which has been linked with organ failure in ICU patients. However, whether oxHDL elicits a ECs-mediated procoagulant phenotype generating organ failure and death, and the underlying molecular mechanism is not known. Therefore, we studied whether oxHDL-treated rats and high-oxHDL ICU patients exhibit a procoagulant phenotype and its association with kidney injury and mortality and the endothelial underlying molecular mechanism. Methods Human ECs, oxHDL-treated rats and ICU patients were subjected to several cellular and molecular studies, coagulation analyses, kidney injury assessment and mortality determination. Results OxHDL-treated ECs showed a procoagulant protein expression reprograming characterized by increased E-/P-selectin and vWF mRNA expression through specific signaling pathways. OxHDL-treated rats exhibited a procoagulant phenotype and modified E-/P-selectin, vWF, TF and t-PA mRNA expression correlating with plasma TF, t-PA and D-dimer. Also, showed increased death events and the relative risk of death, and increased creatinine, urea, BUN/creatinine ratio, KIM-1, NGAL, β2M, and decreased eGFR, all concordant with kidney injury, correlated with plasma TF, t-PA and D-dimer. ICU patients showed correlation between plasma oxHDL and increased creatinine, cystatin, BUN, BUN/creatinine ratio, KIM-1, NGAL, β2M, and decreased GFR. Notably, ICU high-oxHDL patients showed decreased survival. Interestingly, altered coagulation factors TF, t-PA and D-dimer correlated with both increased oxHDL levels and kidney injury markers, indicating a connection between these factors. Conclusion Increased circulating oxHDL generates an endothelial-dependent procoagulant phenotype that associates with acute kidney injury and increased risk of death.