JOSE OTAVIO COSTA AULER JUNIOR
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cirurgia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/08 - Laboratório de Anestesiologia, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/08 - Laboratório de Anestesiologia, Hospital das Clínicas, Faculdade de Medicina - Líder
14 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 14
- TREATMENT WITH HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS IN A PIG MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY: EFFECTS ON MICROVASCULAR ENDOTHELIAL CELLS AND TUBULAR CELLS IN THE KIDNEY(2023) MAIA, Debora Rothstein Ramos; OTSUKI, Denise Aya; RODRIGUES, Camila Eleuterio; ZBORIL, Sabrina; SANCHES, Talita Rojas; NETO, Amaro Nunes Duarte; ANDRADE, Lucia; AULER, Jose Otavio CostaBackground: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 x 106 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappa B) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-kappa B signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.
- The effect of premedication with ketamine, alone or with diazepam, on anaesthesia with sevoflurane in parrots (Amazona aestiva)(2013) PAULA, Valeria Veras; OTSUKI, Denise Aya; AULER JUNIOR, Jose Otavio Costa; NUNES, Talyta Lins; AMBROSIO, Aline Magalhaes; FANTONI, Denise TabacchiBackground: Premedication is rarely used in avian species. The aim of this study was to evaluate the effect of premedication on the quality of sevoflurane induction and anaesthesia in parrots. We hypothesised that premedication would facilitate handling and decrease the minimum anaesthetic dose (MAD). Thirty-six adult parrots were randomly distributed in three groups: group S (n = 12) was premedicated with NaCl 0.9%; group KS (n = 12) was premedicated with 10 mg.kg(-1) ketamine; and group KDS (n = 12) was premedicated with 10 mg.kg(-1) ketamine and 0.5 mg.kg(-1) diazepam, delivered intramuscularly. After induction using 4.5% sevoflurane introduced through a facemask, the MAD was determined for each animal. The heart rate (HR), respiratory rate (RR), systolic arterial blood pressure (SAP), and cloacal temperature (CT) were recorded before premedication (T0), 15 minutes after premedication (T1), and after MAD determination (T2). Arterial blood gas analyses were performed at T0 and T2. The quality of anaesthesia was evaluated using subjective scales based on animal behaviour and handling during induction, maintenance, and recovery. Statistical analyses were performed using analysis of variance or Kruskal-Wallis tests followed by Tukey's or Dunn's tests. Results: The minimal anaesthetic doses obtained were 2.4 +/- 0.37%, 1.7 +/- 0.39%, and 1.3 +/- 0.32% for groups S, KS, and KDS, respectively. There were no differences in HR, RR, or CT among groups, but SAP was significantly lower in group S. Sedation was observed in both the premedicated S-KS and S-KDS groups. There were no differences in the quality of intubation and recovery from anaesthesia among the three groups, although the induction time was significantly shorter in the pre-medicated groups, and the KS group showed less muscle relaxation. Conclusions: Ketamine alone or the ketamine/diazepam combination decreased the MAD of sevoflurane in parrots (Amazona aestiva). Ketamine alone or in combination with diazepam promoted a good quality of sedation, which improved handling and reduced the stress of the birds. All protocols provided safe anaesthesia in this avian species.
- PULSE PRESSURE VARIATION IS COMPARABLE WITH CENTRAL VENOUS PRESSURE TO GUIDE FLUID RESUSCITATION IN EXPERIMENTAL HEMORRHAGIC SHOCK WITH ENDOTOXEMIA(2013) NOEL-MORGAN, Jessica; OTSUKI, Denise Aya; AULER JR., Jose Otavio Costa; FUKUSHIMA, Julia Tizue; FANTONI, Denise TabacchiIntroduction: Pulse pressure variation (PPV) has been proposed as a promising resuscitation goal, but its ability to predict fluid responsiveness has been questioned in various conditions. The purpose of this study was to assess the performance of PPV in predicting fluid responsiveness in experimental hemorrhagic shock with endotoxemia, while comparing it with goals determined by a conventional set of guidelines. Methods: Twenty-seven pigs were submitted to acute hemorrhagic shock with intravenous infusion of endotoxin and randomized to three groups: (i) control; (ii) conventional treatment with crystalloids to achieve and maintain central venous pressure (CVP) 12 to 15 mmHg, mean arterial pressure of 65 mmHg or greater, and SvO(2) (mixed venous oxygen saturation) of 65% or greater; (iii) treatment to achieve and maintain PPV of 13% or less. Parametric data were analyzed by two-way analysis of variance and Tukey test and differences in crystalloid volumes by t test. Predictive values of variables regarding fluid responsiveness were evaluated by receiver operating characteristic curves and multiple logistic regression. Results: Both treatments produced satisfactory hemodynamic recovery, without statistical differences in fluid administration (P = 0.066), but conventional treatment induced higher CVP (P = 0.001). Areas under receiver operating characteristic curves were larger for CVP (0.77; 95% confidence interval, 0.68-0.86) and PPV (0.74; 95% confidence interval, 0.65-0.83), and these variables were further selected by multiple logistic regression as independent predictors of responsiveness. Optimal PPV cutoff was 15%, with false-positive results involving mean pulmonary arterial pressure of 27 mmHg or greater. Conclusions: Acute resuscitation guided by PPV was comparable with the strategy guided by CVP, mean arterial pressure, and SvO(2). Central venous pressure and PPV were individually limited but independently predictive of fluid responsiveness.
- Predictors and their prognostic value for no ROSC and mortality after a non-cardiac surgery intraoperative cardiac arrest: a retrospective cohort study(2019) VANE, Matheus F.; CARMONA, Maria J. C.; PEREIRA, Sergio M.; KERN, Karl B.; TIMERMAN, Sergio; PEREZ, Guilherme; VANE, Luiz Antonio; OTSUKI, Denise Aya; JR, Jose O. C. AulerData on predictors of intraoperative cardiac arrest (ICA) outcomes are scarce in the literature. This study analysed predictors of poor outcome and their prognostic value after an ICA. Clinical and laboratory data before and 24 hours (h) after ICA were analysed as predictors for no return of spontaneous circulation (ROSC) and 24 h and 1-year mortality. Receiver operating characteristic curves for each predictor and sensitivity, specificity, positive and negative likelihood ratios, and post-test probability were calculated. A total of 167,574 anaesthetic procedures were performed, including 158 cases of ICAs. Based on the predictors for no ROSC, a threshold of 13 minutes of ICA yielded the highest area under curve (AUC) (0.867[0.80-0.93]), with a sensitivity and specificity of 78.4% [69.6-86.3%] and 89.3% [80.4-96.4%], respectively. For the 1-year mortality, the GCS without the verbal component 24 h after an ICA had the highest AUC (0.616 [0.792-0.956]), with a sensitivity of 79.3% [65.5-93.1%] and specificity of 86.1 [74.4-95.4]. ICA duration and GCS 24 h after the event had the best prognostic value for no ROSC and 1-year mortality. For 24 h mortality, no predictors had prognostic value.
- Evaluation of Neuronal Apoptosis Precursors in an Experimental Model of Acute Normovolemic Hemodilution(2014) FRAZILIO, Fabricio O.; OTSUKI, Denise Aya; NOEL-MORGAN, Jessica; MAXIMINO, Jessica Ruivo; OLIVEIRA, Gabriela Pintar; CHADI, Gerson; AULER JR., Jose Otavio Costa; FANTONI, Denise TabacchiBackground: The effects of acute anemia on neuronal cells and the safe limits of hematocrit are not well established. The objective of this study was to evaluate neuronal pro-and anti-apoptotic Bax and Bcl-x proteins, caspase-3 and -9 activity, and DNA fragmentation after acute normovolemic hemodilution (ANH). Methods: Twenty-four pigs were anesthetized and randomized into 4 groups: Sham, ANH to 15% hematocrit (ANH15%), ANH to 10% hematocrit (ANH10%) and hypoxia (Hx). ANH was achieved by simultaneous blood withdrawal and hydroxyethyl starch infusion. Hx consisted of ventilation with a 6% inspired oxygen fraction for 60 minutes. Bax and Bcl-x proteins as well as DNA fragmentation were evaluated in cortical nuclear and mitochondrial fractions. Caspase-3 and -9 activity was evaluated in the cortical mitochondrial and hippocampal cytosolic fractions. The data were compared using analysis of variance followed by Tukey's test (P<0.05). Results: No changes were observed in Bax protein expression after hemodilution in the ANH15% and ANH10% groups compared to the Sham group. Bax expression in the Hx group was increased in the nuclear and mitochondrial fractions compared to all other groups. No significant difference was observed in Bcl-x expression. Caspase-3 and -9 activity in the cytosolic and mitochondrial fractions was different in the Hx group compared to all other groups. No statistical significance in DNA fragmentation was found among the Sham, ANH15% or ANH10% groups. Conclusion: ANH to 10 and 15% hematocrit did not induce alterations in apoptosis precursors, suggesting that cerebral oxygenation was preserved during these anemic states.
- Heart Rate Variability Analysis in an Experimental Model of Hemorrhagic Shock and Resuscitation in Pigs(2015) SALOMAO JR., Edgard; OTSUKI, Denise Aya; CORREA, Andre Luis; FANTONI, Denise Tabacchi; SANTOS, Fernando dos; IRIGOYEN, Maria Claudia; AULER JR., Jose Otavio CostaBackground The analysis of heart rate variability (HRV) has been shown as a promising non-invasive technique for assessing the cardiac autonomic modulation in trauma. The aim of this study was to evaluate HRV during hemorrhagic shock and fluid resuscitation, comparing to traditional hemodynamic and metabolic parameters. Methods Twenty anesthetized and mechanically ventilated pigs were submitted to hemorrhagic shock (60% of estimated blood volume) and evaluated for 60 minutes without fluid replacement. Surviving animals were treated with Ringer solution and evaluated for an additional period of 180 minutes. HRV metrics (time and frequency domain) as well as hemodynamic and metabolic parameters were evaluated in survivors and non-survivors animals. Results Seven of the 20 animals died during hemorrhage and initial fluid resuscitation. All animals presented an increase in time-domain HRV measures during haemorrhage and fluid resuscitation restored baseline values. Although not significantly, normalized low-frequency and LF/HF ratio decreased during early stages of haemorrhage, recovering baseline values later during hemorrhagic shock, and increased after fluid resuscitation. Non-surviving animals presented significantly lower mean arterial pressure (43 +/- 7vs57 +/- 9 mmHg, P<0.05) and cardiac index (1.7 +/- 0.2vs2.6 +/- 0.5 L/min/m(2), P<0.05), and higher levels of plasma lactate (7.2 +/- 2.4vs3.7 +/- 1.4 mmol/L, P<0.05), base excess (-6.8 +/- 3.3vs-2.3 +/- 2.8 mmol/L, P<0.05) and potassium (5.3 +/- 0.6vs4.2 +/- 0.3 mmol/L, P<0.05) at 30 minutes after hemorrhagic shock compared with surviving animals. Conclusions The HRV increased early during hemorrhage but none of the evaluated HRV metrics was able to discriminate survivors from non-survivors during hemorrhagic shock. Moreover, metabolic and hemodynamic variables were more reliable to reflect hemorrhagic shock severity than HRV metrics.
- Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis(2022) CARNICELLI, Paulo; OTSUKI, Denise Aya; MONTEIRO FILHO, Adalberto; KAHVEGIAN, Marcia Aparecida Portela; IDA, Keila Kazue; AULER-JR, Jose Otavio Costa; ROUBY, Jean-Jacques; FANTONI, Denise TabacchiPurpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 x 10(9) cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 +/- 9.7 vs. 32.5 +/- 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 +/- 1 vs. 9.61 +/- 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 +/- 9.6 vs. 63.5 +/- 9.2%, P = 0.026), and increased plasma lactate (3.7 +/- 0.5 vs. 5.5 +/- 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 +/- 0.4 vs. 14.4 +/- 0.3 mL/m(2); P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 +/- 0.2 vs. 2.4 +/- 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.
- Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study(2023) KEMPER, Daniella Aparecida Godoi; OTSUKI, Denise Aya; MAIA, Debora Rothstein Ramos; MOSSOCO, Cristina de Oliveira; MARCASSO, Rogerio Anderson; CUNHA, Ligia Cristina Camara; JR, Jose Otavio Costa Auler; FANTONI, Denise TabacchiBackground: Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. Methods: Twenty pigs were randomly assigned to Control group (n = 10), which received saline solution; or to Sildenafil group (n = 10), which received sildenafil orally (100 mg). After 30 min-utes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4 & mu;g.kg-1.h-1) for 180 minutes. We evaluated hemodynamic and oxy-genation functions, and also lung histology and plasma cytokine (TNFa, IL-1(3, IL6, and IL10) and troponin I response. Results: Significant hemodynamic alterations were observed after 30 minutes of LPS contin-uous infusion, mainly in pulmonary arterial pressure (from Baseline 19 & PLUSMN; 2 mmHg to LPS30 52 & PLUSMN; 4 mmHg, p < 0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411 & PLUSMN; 29 to LPS180 334 & PLUSMN; 49, p < 0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35 & PLUSMN; 4 mmHg at LPS30, p < 0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly.Conclusion: Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.& COPY; 2021 Published by Elsevier Editora Ltda. on behalf of Sociedade Brasileira de Anestesiologia. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
- Sevoflurane preconditioning during myocardial ischemia-reperfusion reduces infarct size and preserves autonomic control of circulation in rats(2016) PASQUALIN, Rubens Campana; MOSTARDA, Cristiano Teixeira; SOUZA, Leandro Ezequiel de; VANE, Matheus Fachini; SIRVENTE, Raquel; OTSUKI, Denise Aya; TORRES, Marcelo Luis Abramides; IRIGOYEN, Maria Claudia Costa; AULER, Jose Otavio CostaPURPOSE: To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia-reperfusion. METHODS: Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. RESULTS: The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. CONCLUSION: Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period.
- Effects of terlipressin as early treatment for protection of brain in a model of haemorrhagic shock(2015) IDA, Keila Kazue; OTSUKI, Denise Aya; SASAKI, Adolfo Toshiro Cotarelli; BORGES, Emilyn Silva; CASTRO, Letcia Urbano Cardoso; SANCHES, Talita Rojas; SHIMIZU, Maria-Heloisa Massola; ANDRADE, Lcia Conceicao; AULER JR., Jose-Otavio Costa; DYSON, Alex; SMITH, Kenneth John; ROCHA FILHO, Joel Avancini; MALBOUISSON, Luiz-Marcelo SaIntroduction: We investigated whether treatment with terlipressin during recovery from hypotension due to haemorrhagic shock (HS) is effective in restoring cerebral perfusion pressure (CPP) and brain tissue markers of water balance, oxidative stress and apoptosis. Methods: In this randomised controlled study, animals undergoing HS (target mean arterial pressure (MAP) 40 mmHg for 30 minutes) were randomised to receive lactated Ringer's solution (LR group; n = 14; volume equal to three times the volume bled), terlipressin (TERLI group; n = 14; 2-mg bolus), no treatment (HAEMO group; n = 12) or sham (n = 6). CPP, systemic haemodynamics (thermodilution technique) and blood gas analyses were registered at baseline, shock and 5, 30, 60 (T60), 90 and 120 minutes after treatment (T120). After the animals were killed, brain tissue samples were obtained to measure markers of water balance (aquaporin-4 (AQP4)), Na+-K+-2Cl(-) co-transporter (NKCC1)), oxidative stress (thiobarbituric acid reactive substances (TBARS) and manganese superoxide dismutase (MnSOD)) and apoptotic damage (Bcl-x and Bax). Results: Despite the HS-induced decrease in cardiac output (CO) and hyperlactataemia, resuscitation with terlipressin recovered MAP and resulted in restoration of CPP and in cerebral protection expressed by normalisation of AQP4, NKCC1, TBARS and MnSOD expression and Bcl-x/Bax ratio at T60 and T120 compared with sham animals. In the LR group, CO and blood lactate levels were recovered, but the CPP and MAP were significantly decreased and TBARS levels and AQP4, NKCC1 and MnSOD expression and Bcl-x/Bax ratio were significantly increased at T60 and T120 compared with the sham group. Conclusions: During recovery from HS-induced hypotension, terlipressin was effective in normalising CPP and cerebral markers of water balance, oxidative damage and apoptosis. The role of this pressor agent on brain perfusion in HS requires further investigation.