RESUMO
OBJECTIVE: The hemolytic product free-hemoglobin (fHb) reduces nitric oxide (NO) bioavailability. The present study aims to establish whether administration of different blood transfusions result in increased circulating fHb levels and NO consumption with effects on arterial NO-dependent blood flow in patients undergoing CABG surgery. METHODS: Ninety-five consecutive patients undergoing elective CABG surgery were prospectively divided in four groups based on blood transfusion requirements during surgery: stored blood cells (SBC, n. 21), intraoperative autologous salvaged blood (ASB, n. 25), SBC and ASB (n.22), no transfusion (control, n. 27). Blood samples were collected before and after intervention to analyse plasma levels of fHb and NO consumption. Endothelium-dependent relaxation was assessed in left internal mammary artery (LIMA) rings harvested before chest closure. Peripheral artery tonometry was assessed after intervention. RESULTS: Transfusions with SBC increased plasma fHb (p<0.05). Transfusions of ASB resulted in higher plasma fHb compared to SBC (p<0.01). fHb concentrations directly correlated with NO consumption (r=0.65, p<0.001). Maximal endothelium-dependent relaxation in LIMA was significantly attenuated in SBC and ASB patients compared to control (15.2±3.1% vs 21.1±2.5% vs 43±5.0% respectively; p<0.01). Significant correlations were identified between the aortic pressure wave velocity, plasma fHb concentration and NO consumption (p<0.01). CONCLUSIONS: Intraoperative blood transfusions and particularly autologous salvaged blood impair endothelium-dependent relaxation through NO scavenging by fHb. These findings obtained in vitro and in vivo provide new insights into the adverse relation between blood transfusions and patient outcome.
Assuntos
Transfusão de Sangue Autóloga/efeitos adversos , Transfusão de Sangue , Ponte de Artéria Coronária/efeitos adversos , Endotélio Vascular/fisiopatologia , Artéria Torácica Interna/fisiopatologia , Artéria Torácica Interna/cirurgia , Vasodilatação , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Endotélio Vascular/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Recuperação de Sangue Operatório , Estudos Prospectivos , Análise de Onda de Pulso , Rigidez VascularRESUMO
In order to assess mechanisms underlying inflammatory activation during extracorporeal circulation (ECC), several small animal models of ECC have been proposed recently. The majority of them are based on home-made, nonstandardized, and hardly reproducible oxygenators. The present study has generated fundamental information on the role of oxygenator of ECC in activating inflammatory signaling pathways on leukocytes, leading to systemic inflammatory response, and organ dysfunction. The present results suggest that experimental animal models of ECC used in translational research on inflammatory response should be based on standardized, reproducible oxygenators with clinical characteristics.
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Circulação Extracorpórea , Leucócitos/metabolismo , Oxigenadores , Animais , Inflamação/metabolismo , Modelos AnimaisRESUMO
Pulmonary arterial hypertension is a common complication of congenital heart defects with left-to-right shunts. Current preclinical models do not reproduce clinical characteristics of shunt-related pulmonary hypertension. Aorto-caval shunt was firstly described as a model of right ventricle volume overload. The pathophysiology and the possible determination of pulmonary arterial hypertension of different periods of shunt exposure are still undefined. A method to create standardized, reproducible aorto-caval shunt was developed in growing rats (260±40 g). Three groups of animals were considered: shunt exposure for 10 weeks, shunt exposure for 20 weeks and control (sham laparotomy). Echocardiography and magnetic resonance revealed increased right ventricular end diastolic area in shunt at 10 weeks compared to control. Hemodynamic analysis demonstrated increased right ventricular afterload and increased effective pulmonary arterial elastance (Ea) in shunt at 20 weeks compared to control (1.29±0.20 vs. 0.14±0.06 mmHg/µl, p=0.004). At the same time point, the maximal slope of end-systolic pressure-volume relationship (Ees) decreased (0.5±0.2 mmHg/ml vs. 1.2±0.3, p<0.001). Consequently, right ventricular-arterial coupling was markedly deteriorated with a ≈50% decrease in the ratio of end-systolic to pulmonary artery elastance (Ees/Ea). Finally, left ventricular preload diminished (≈30% decrease in left ventricular end-diastolic volume). Histology demonstrated medial hypertrophy and small artery luminal narrowing. Chronic exposure to aorto-caval shunt is a reliable model to produce right ventricular volume overload and secondary pulmonary arterial hypertension. This model could be an alternative with low mortality and high reproducibility for investigators on the underlying mechanisms of shunt-related pulmonary hypertension.
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Hipertensão Pulmonar/fisiopatologia , Animais , Aorta/patologia , Pressão Sanguínea , Modelos Animais de Doenças , Ecocardiografia , Ventrículos do Coração/patologia , Hemodinâmica , Pulmão/irrigação sanguínea , Imageamento por Ressonância Magnética , Masculino , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Volume Sistólico , Ultrassonografia Doppler , Remodelação VascularRESUMO
INTRODUCTION: Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA. METHODS: Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 µg/kg/min; n = 15), epinephrine (0.1 µg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter. RESULTS: The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan. CONCLUSIONS: Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA.
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Parada Circulatória Induzida por Hipotermia Profunda , Epinefrina/farmacologia , Coração/efeitos dos fármacos , Hidrazonas/farmacologia , Piridazinas/farmacologia , Animais , Western Blotting , Ponte Cardiopulmonar , Hemodinâmica/efeitos dos fármacos , Técnicas Imunoenzimáticas , Masculino , Fosforilação , Distribuição Aleatória , Ratos , Ratos Wistar , Reaquecimento , Simendana , Troponina I/sangueRESUMO
. Preparedness for emergencies: strategies to increase the supply of beds and advanced intensive skills. INTRODUCTION: The recent pandemic has highlighted the importance of emergency preparedness plans. In addition to technological and structural resources, it is essential to have professionals with skills that allow them to safely work in intensive care areas. AIM: The aim of the contribution is to propose an intervention model to develop the skills of nurses of operatory theatres or intensive care to enable them to work safely in critical care settings. METHODS: A plan was devised, involving a multiprofessional group to increase the number of beds in the intensive and semi-intensive care areas, as well as to train staff, hypothesising the activities to be reduced by moving staff to different areas. RESULTS: The proposed organisational model could be implemented in other hospitals; it guarantees emergency preparedness and the expansion of the skills of the staff involved. CONCLUSIONS: Nursing staff with advanced skills should be readily available to safely guarantee the expansion of intensive care beds. The current division between intensive and semi-intensive settings could be revised in favour of a single critical care area.
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Emergências , Hospitais , Humanos , Cuidados CríticosRESUMO
Therapeutic hypothermia is recommended by international guidelines after cardio-circulatory arrest. However, the effects of different temperatures during the first 24 hours after deep hypothermic circulatory arrest (DHCA) for aortic arch surgery on survival and neurologic outcome are undefined. We hypothesize that temperature variation after aortic arch surgery is associated with survival and neurologic outcome. In the period 2010-2014, a total of 210 consecutive patients undergoing aortic arch surgery with DHCA were included. They were retrospectively divided into three groups by median nasopharyngeal temperature within 24 hours after rewarming: hypothermia (<36°C; n = 65), normothermia (36-37°C; n = 110), and hyperthermia (>37°C; n = 35). Multivariate stepwise logistic and linear regressions were performed to determine whether different temperature independently predicted 30-day mortality, stroke incidence, and neurologic outcome assessed by cerebral performance category (CPC) at hospital discharge. Compared with normothermia, hyperthermia was independently associated with a higher risk of 30-day mortality (28.6% vs. 10.9%; odds ratio [OR] 2.8; 95% confidence interval [CI], 1.1-8.6; p = 0.005), stroke incidence (64.3% vs. 9.1%; OR 9.1; 95% CI, 2.7-23.0; p = 0.001), and poor neurologic outcome (CPC 3-5) (68.8% vs. 39.6%; OR 4.8; 95% CI, 1.4-8.7; p = 0.01). No significant differences were demonstrated between hypothermia and normothermia. Postoperative hypothermia is not associated with a better outcome after aortic arch surgery with DHCA. However, postoperative hyperthermia (>37°C) is associated with high stroke incidence, poor neurologic outcome, and increased 30-day mortality. Target temperature management in the first 24 hours after surgery should be evaluated in prospective randomized trials.
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Parada Circulatória Induzida por Hipotermia Profunda , Reaquecimento , Adulto , Idoso , Aorta Torácica/cirurgia , Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Parada Circulatória Induzida por Hipotermia Profunda/métodos , Parada Circulatória Induzida por Hipotermia Profunda/mortalidade , Parada Circulatória Induzida por Hipotermia Profunda/estatística & dados numéricos , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reaquecimento/efeitos adversos , Reaquecimento/métodos , Reaquecimento/mortalidade , Reaquecimento/estatística & dados numéricos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , TemperaturaRESUMO
BACKGROUND: This study examined the acute effect of intravenous S-nitroso human serum albumin (S-NO-HSA) infusion on overall hemodynamics and oxidative stress in a chronic left-to-right shunt-induced pulmonary arterial hypertension model with right ventricle (RV) failure. METHODS: An aortocaval fistula (pulmonary-to-systemic blood flow ratio [Qp/Qs] > 2.0) was surgically created in 50 male Wistar rats. After 10 weeks, they were randomly treated with S-NO-HSA (n = 20) or human serum albumin (HSA; n = 25) infusion (0.5 µmol/kg/h) for 60 minutes. A sham group (n = 10) received S-NO-HSA. RV contractility, RV-vascular coupling, and ventricular interdependence were assessed in vivo at different pre-loads by biventricular conductance catheters. Heart and lung biopsy specimens were obtained for determination of high-energy phosphates, oxidative stress (oxidized glutathione/reduced glutathione), and endothelial nitric oxide synthase protein expression. RESULTS: S-NO-HSA, compared with HSA infusion, reduced RV afterload expressed by effective pulmonary arterial elastance (Ea; 0.49 ± 0.3 vs 1.2 ± 0.2 mm Hg/ml; p = 0.0005) and improved RV diastolic function (slope of end-diastolic pressure-volume relationship) as well as contractility indicated by slope of end-systolic pressure-volume relationship (Ees). Therefore an increase in efficiency of ventricular-vascular coupling (Ees/Ea) occurred after S-NO-HSA (0.35 ± 0.17 to 0.94 ± 0.21; p = 0.005), but not HSA infusion, leading to positive effect on ventricular interdependence with increased left ventricular stroke volume (56% ± 4% vs 19% ± 5%; p = 0.0013). S-NO-HSA, compared with HSA, treatment improved adenosine 5'-triphosphate (13.9 ± 1.1 vs 7.0 ± 1.8 µmol/g protein) and phosphocreatine (5.9 ± 3.3 vs 1.9 ± 0.6 µmol/g protein; p = 0.01) RV content and decreased the tissue oxidized glutathione/reduced glutathione ratio (p = 0.001). CONCLUSIONS: S-NO-HSA reduces pulmonary hypertension and improves RV systolic and diastolic function and RV-arterial coupling, with a positive effect on ventricular interdependence by increasing energetic reserve and reducing oxidative stress.