DENISE AYA OTSUKI
Projetos de Pesquisa
Unidades Organizacionais
LIM/08 - Laboratório de Anestesiologia, Hospital das Clínicas, Faculdade de Medicina
11 resultados
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conferenceObject RESUSCITATION WITH FLUID OR TERLIPRESSLN DOES NOT INFLUENCE COAGULATION STATUS IN A MODEL OF SEVERE CONTROLLED HAEMORRHAGIC SHOCK(2012) SASAKI, A. T. C.; OTSUKI, D. A.; IDA, K. K.; AULER JR., J. O. C.; MALBOUISSON, L. M. S.- Terlipressin combined with conservative fluid management attenuates hemorrhagic shock-induced acute kidney injury in rats(2022) CASTRO, Leticia Urbano Cardoso; OTSUKI, Denise Aya; SANCHES, Talita Rojas; SOUZA, Felipe Lima; SANTINHO, Mirela Aparecida Rodrigues; SILVA, Cleonice da; NORONHA, Irene de Lourdes; DUARTE-NETO, Amaro Nunes; GOMES, Samirah Abreu; MALBOUISSON, Luiz-Marcelo Sa; ANDRADE, LuciaHemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer's (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30-40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn (liberal fluid management); at 2 times the volume (conservative fluid management), plus terlipressin (10 mu g/100 g body weight); and at an equal volume (conservative fluid management), plus terlipressin (10 mu g/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, interleukin 6 levels, interleukin 18 levels, and nuclear factor kappa B expression. In terlipressin-treated animals, there was also significantly higher angiotensin II type 1 receptor expression and normalization of arginine vasopressin 1a receptor expression. Terlipressin associated with conservative fluid management could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the arginine vasopressin 1a receptor.
- Computed Tomography Assessment of Tidal Lung Overinflation in Domestic Cats Undergoing Pressure-Controlled Mechanical Ventilation During General Anesthesia(2022) MARTINS, Alessandro R. C.; AMBROSIO, Aline M.; FANTONI, Denise T.; PINTO, Ana Carolina B. C. F.; VILLAMIZAR-MARTINEZ, Lenin Arturo; SOARES, Joao H. N.; OTSUKI, Denise A.; MALBOUISSON, Luiz Marcelo S.ObjectiveThis study aimed to evaluate lung overinflation at different airway inspiratory pressure levels using computed tomography in cats undergoing general anesthesia. Study DesignProspective laboratory study. AnimalsA group of 17 healthy male cats, aged 1.9-4.5 years and weighing 3.5 +/- 0.5 kg. MethodsSeventeen adult male cats were ventilated in pressure-controlled mode with airway pressure stepwise increased from 5 to 15 cmH(2)O in 2 cmH(2)O steps every 5 min and then stepwise decreased. The respiratory rate was set at 15 movements per min and end-expiratory pressure at zero (ZEEP). After 5 min in each inspiratory pressure step, a 4 s inspiratory pause was performed to obtain a thoracic juxta-diaphragmatic single slice helical CT image and to collect respiratory mechanics data and an arterial blood sample. Lung parenchyma aeration was defined as overinflated, normally-aerated, poorly-aerated, and non-aerated according to the CT attenuation number (-1,000 to -900 HU, -900 to -500 HU, -500 to -100 HU, and -100 to +100 HU, respectively). ResultAt 5 cmH(2)O airway pressure, tidal volume was 6.7 +/- 2.2 ml kg(-1), 2.1% (0.3-6.3%) of the pulmonary parenchyma was overinflated and 84.9% (77.6%-87.6%) was normally inflated. Increases in airway pressure were associated with progressive distention of the lung parenchyma. At 15 cmH(2)O airway pressure, tidal volume increased to 31.5 +/- 9.9 ml kg(-1) (p < 0.001), overinflated pulmonary parenchyma increased to 28.4% (21.2-30.6%) (p < 0.001), while normally inflated parenchyma decreased 57.9% (53.4-62.8%) (p < 0.001). Tidal volume and overinflated lung fraction returned to baseline when airway pressure was decreased. A progressive decrease was observed in arterial carbon dioxide partial pressure (PaCO2) and end-tidal carbon dioxide (ETCO2) when the airway pressures were increased above 9 cmH(2)O (p < 0.001). The increase in airway pressure promoted an elevation in pH (p < 0.001).
- Impact of Cardiopulmonary Bypass on Respiratory Mucociliary Function in an Experimental Porcine Model(2015) SANCHEZ-VELIZ, Rodrigo; CARMONA, Maria Jose; OTSUKI, Denise Aya; FREITAS, Claudia; BENICIO, Anderson; NEGRI, Elnara Marcia; MALBOUISSON, Luiz MarceloBackground The impact of cardiac surgery using cardiopulmonary bypass (CPB) on the respiratory mucociliary function is unknown. This study evaluated the effects of CPB and interruption of mechanical ventilation on the respiratory mucociliary system. Methods Twenty-two pigs were randomly assigned to the control (n = 10) or CPB group (n = 12). After the induction of anesthesia, a tracheostomy was performed, and tracheal tissue samples were excised (T0) from both groups. All animals underwent thoracotomy. In the CPB group, an aorto-bicaval CPB was installed and maintained for 90 minutes. During the CPB, mechanical ventilation was interrupted, and the tracheal tube was disconnected. A second tracheal tissue sample was obtained 180 minutes after the tracheostomy (T180). Mucus samples were collected from the trachea using a bronchoscope at T0, T90 and T180. Ciliary beat frequency (CBF) and in situ mucociliary transport (MCT) were studied in ex vivo tracheal epithelium. Mucus viscosity (MV) was assessed using a cone-plate viscometer. Qualitative tracheal histological analysis was performed at T180 tissue samples. Results CBF decreased in the CPB group (13.1 +/- 1.9 Hz vs. 11.1 +/- 2.1 Hz, p < 0.05) but not in the control group (13.1 +/- 1 Hz vs. 13 +/- 2.9 Hz). At T90, viscosity was increased in the CPB group compared to the control (p < 0.05). No significant differences were observed in in situ MCT. Tracheal histology in the CPB group showed areas of ciliated epithelium loss, submucosal edema and infiltration of inflammatory cells. Conclusion CPB acutely contributed to alterations in tracheal mucocilliary function.
- Can a Therapeutic Strategy for Hypotension Improve Cerebral Perfusion and Oxygenation in an Experimental Model of Hemorrhagic Shock and Severe Traumatic Brain Injury?(2023) BALZI, Ana Paula de Carvalho Canela; OTSUKI, Denise Aya; ANDRADE, Lucia; PAIVA, Wellingson; SOUZA, Felipe Lima; AURELIANO, Luiz Guilherme Cernaglia; MALBOUISSON, Luiz Marcelo SaBackgroundRestoration of brain tissue perfusion is a determining factor in the neurological evolution of patients with traumatic brain injury (TBI) and hemorrhagic shock (HS). In a porcine model of HS without neurological damage, it was observed that the use of fluids or vasoactive drugs was effective in restoring brain perfusion; however, only terlipressin promoted restoration of cerebral oxygenation and lower expression of edema and apoptosis markers. It is unclear whether the use of vasopressor drugs is effective and beneficial during situations of TBI. The objective of this study is to compare the effects of resuscitation with saline solution and terlipressin on cerebral perfusion and oxygenation in a model of TBI and HS.MethodsThirty-two pigs weighing 20-30 kg were randomly allocated into four groups: control (no treatment), saline (60 ml/kg of 0.9% NaCl), terlipressin (2 mg of terlipressin), and saline plus terlipressin (20 ml/kg of 0.9% NaCl + 2 mg of terlipressin). Brain injury was induced by lateral fluid percussion, and HS was induced through pressure-controlled bleeding, aiming at a mean arterial pressure (MAP) of 40 mmHg. After 30 min of circulatory shock, resuscitation strategies were initiated according to the group. The systemic and cerebral hemodynamic and oxygenation parameters, lactate levels, and hemoglobin levels were evaluated. The data were subjected to analysis of variance for repeated measures. The significance level established for statistical analysis was p < 0.05.ResultsThe terlipressin and saline plus terlipressin groups showed an increase in MAP that lasted until the end of the experiment (p < 0.05). There was a notable increase in intracranial pressure in all groups after starting treatment for shock. Cerebral perfusion pressure and cerebral oximetry showed no improvement after hemodynamic recovery in any group. The groups that received saline at resuscitation had the lowest hemoglobin concentrations after treatment.ConclusionsThe treatment of hypotension in HS with saline and/or terlipressin cannot restore cerebral perfusion or oxygenation in experimental models of HS and severe TBI. Elevated MAP raises intracranial pressure owing to brain autoregulation dysfunction caused by TBI.
- Effects of Positive End-expiratory Pressure Titration and Recruitment Maneuver on Lung Inflammation and Hyperinflation in Experimental Acid Aspiration-induced Lung Injury(2012) AMBROSIO, Aline M.; LUO, Rubin; FANTONI, Denise T.; GUTIERRES, Claudia; LU, Qin; GU, Wen-Jie; OTSUKI, Denise A.; MALBOUISSON, Luiz M. S.; AULER JR., Jose O. C.; ROUBY, Jean-JacquesBackground: In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods: Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results: Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion: In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.
conferenceObject IMPACT OF DIFFERENT HAEMODYNAMIC RESUSCITATION STRATEGIES ON BRAIN PERFUSION AND TISSUE EDEMA MARKERS IN A MODEL OF SEVERE HAEMORRHAGIC SHOCK(2013) MALBOUISSON, L. M.; IDA, K. K.; OTSUKI, D. A.; CASTRO, L. U.; SANCHES, T. R.; SHIMIZU, M. M.; ANDRADE, L. C.; CARMONA, M. C.- Myocardial protection induced by fentanyl in pigs exposed to high-dose adrenaline(2015) LUZ, Vinicius Fernando da; OTSUKI, Denise Aya; GONZALEZ, Maria Margarita Castro; NEGRI, Elnara Marcia; CALDINI, Elia Garcia; DAMACENO-RODRIGUES, Nilsa Regina; MALBOUISSON, Luiz Marcelo Sa; VIANA, Bruno Goncalves; VANE, Matheus Fachini; CARMONA, Maria Jose CarvalhoThe use of high doses of adrenaline is common in critical patients, especially during cardiac arrest. During these situations, myocardial dysfunction can be a result of multiple factors, including adrenaline use. In addition, opioids have been shown to have anti-arrhythmic and anti-ischemic mechanisms that may confer cardiac protection. This study aimed to evaluate the effects of fentanyl on myocardial function in pigs exposed to high-dose adrenaline. After institutional ethics committee approval, 26 pigs were randomly allocated to receive either 20 mu g/kg fentanyl (n = 10; fentanyl group) administered 5 min before five doses of adrenaline (20 mu g/kg), equivalent-volume saline (n = 10; saline group) using the same adrenaline dosing protocol, or neither fentanyl nor adrenaline (n = 6; sham group). The fentanyl group showed lower levels of troponin at the end of the sixth hour compared with the saline group (1.91 +/- 1.47 vs 5.44 +/- 5.35 ng/mL, P = 0.019). Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. The conclusion was reached that fentanyl attenuates myocardial injury caused by high-dose adrenaline without blunting the hemodynamic effect of adrenaline.
conferenceObject TERLIPRESSLN IS SUPERIOR TO LACTATED RLNGER SOLUTION FOR CEREBRAL PERFUSION PRESSURE DURING RESUSCITATION IN A MODEL OF HAEMORRHAGIC SHOCK(2012) IDA, K. K.; OTSUKI, D. A.; SASAKI, A. T. C.; AULER JR., J. O. C.; MALBOUISSON, L. M. S.- 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.