Fluids are used for intravenous infusion during practically all surgeries, but several different compositions are available on the market. Crystalloid fluids comprise lactated or acetated Ringer solutions, normal saline, Plasma-Lyte, hypertonic saline, and glucose. They lack allergic properties but are prone to cause peripheral tissue oedema. Their turn­ over is governed by physiological factors such as dehydration and drug effects. Colloid fluids include hydroxyethyl starch, albumin, dextran, and gelatin. These fluids have various degrees of allergic properties and do not promote peripheral oedema. Their half-life is usually about hours. Factors increasing the turnover rate are poorly known but might include inflammatory states. Current debates include the widespread use of normal saline, which should be replaced by Ringer’s or Plasma-Lyte in most situations, and the kidney damage associated with the use of starch in septic patients. New studies show that hypertonic saline does not improve survival or neurological damage in prehospital care.

Hemodiluição normovolêmica aguda é um procedimento utilizado para diminuir a necessidade de transfusões sangüíneas em diversas cirurgias de grande porte. Poucos trabalhos avaliam as alterações hemodinâmicas e perfusão tecidual através de estudo ecocardiográfico e tonometria gástrica. Foram utilizados 23 porcos (peso 46.6 ± 6.0 kg) anestesiados com quetamina, fentanil e propofol e instrumentados para monitorização hemodinâmica convencional. Os animais foram randomizados em três grupos 30 minutos após estabilização da anestesia: Grupo I (Controle), Grupo II (amido hidroxietílico) e Grupo III (Ringer lactato). Os animais do grupo II e III foram submetidos ao protocolo de hemodiluição com hematócrito alvo de 15%. A retirada de sangue foi realizada em 30 minutos e a expansão plasmática feita simultaneamente com amido hidroxietílico ou Ringer lactato nas proporções de 1:1 ou 1:3 em relação ao sangue retirado. Os parâmetros hemodinâmicos e de oxigenação, pH gástrico, ecocardiografia transesofágica (fração de ejeção através do método Simpson) foram coletados antes da hemodiluição (T0), no fim do procedimento de hemodiluição (T1) e após uma e duas horas (T2, T3). Os dados foram submetidos a análise de variância para medidas repetidas, seguida pelo teste Tukey e teste T student. Resultados: Em relação aos parâmetros do grupo controle, não houve diferença significante durante todo o procedimento. No grupo II e grupo III, houve aumento no índice cardíaco após hemodiluição (T0=5,80±1,46; T1=10,64±1,69 L.min-1.m2 e T0=5,53±1,18, T1=7,91±1,40 L.min-1.m2 respectivamente), e diminuição do índice de resistência vascular sistêmica (T0=1753±336, T1=822±140 dina.s.cm-5.m-2 e T0=1673±566, T1=1026±190 dina.s.cm-5.m-2 respectivamente), ambos estatisticamente significante. A fração de ejeção apresentou aumento significativo após a hemodiluição no grupo II. O pH gástrico diminuiu significativamente no grupo III. O lactato arterial aumentou de forma significante no grupo III após a hemodiluição. A microscopia eletrônica do ventrículo esquerdo mostraram discreta destruição de miofilamentos no grupo II. Houve destruição importante nas miofibrilas no grupo III. Conclusão: Estes resultados sugerem que na hemodiluição moderada a grave, o amido hidroxietílico consegue preservar melhor a estabilidade hemodinâmica do que a solução de Ringer lactato. / Normovolemic acute hemodilution is a procedure utilized to decrease the needs of blood transfusion during a variety of surgical procedures. Nevertheless, there are few works that evaluate its pulmonary effects as well as hemodynamic changes by means of echocardiography and tonometric evaluation. Methods: 23 anesthetized pigs (weight 46.6 ± 6.0 kg) were instrumented for standard hemodynamic monitoring. In order to prevent possible effects of inhaled anesthetics on pulmonary mechanics, intravenous anesthesia was chosen and consisted of ketamine, fentanyl and propofol administered throughout the study. Thirty minutes after anesthesia stabilization animals were randomized in three groups: Group I (Control), Group II (hydroxyethyl starch) and Group III (Lactated Ringer’s). Animals of group II and III were submitted to acute normovolemic hemodilution to reach a pre-established hematocrit around 15%. Blood withdrawal was accomplished in thirty minutes and plasma expansion was performed simultaneously with hydroxyethyl starch or Lactated Ringer’s administered in a proportion of 1:1 or 3:1 in relation to the amount of bloods withdrawn. Hemodynamic, gastric pH, transesophageal echography (ejection fraction, by Simpon method) and oxygen transport were measured before blood withdrawal (T0), at the end of hemodilution (T1), one and two hours after the end of hemodilution (T2, T3). Data were submitted to analysis of Variance for repeated measures followed by the Tukey test and also to a student T test. Results: In regard to all parameters of Group I (Control), there were no significant difference during the whole procedure. In Group II and Group III, there was an increase in cardiac index after hemodilution (T0=5.80±1.46; T1=10.64±1.69 L.min-1.m2 and T0=5.53±1.18, T1=7.91±1.40 L.min-1.m2), and a decrease in systemic vascular resistance index (T0=1753±336, T1=822±140 dyne.s.cm-5.m-2 and T0=1673±566, T1=1026±190 dyne.s.cm-5.m-2), both statistically significant. Ejection Fraction increased significantly after hemodilution in group II. Gastric pH decreased significantly in Group III, and arterial lactate increased significantly after hemodilution in group III. Electron microscopy of left ventricular bipsies showed a slight destruction in filament and preserved myofibrillar ultrastructure in group II. There was important destruction in myofibrillar ultrastructure in group III. Conclusion: These results suggest that in severe hemodilution, hydroxyethyl starch preserves hemonodynamic stability better than Lactate Ringer’s.

Hemodiluição normovolêmica aguda é um procedimento utilizado para diminuir a necessidade de transfusões sangüíneas em diversas cirurgias de grande porte. Poucos trabalhos avaliam as alterações hemodinâmicas e perfusão tecidual através de estudo ecocardiográfico e tonometria gástrica. Foram utilizados 23 porcos (peso 46.6 ± 6.0 kg) anestesiados com quetamina, fentanil e propofol e instrumentados para monitorização hemodinâmica convencional. Os animais foram randomizados em três grupos 30 minutos após estabilização da anestesia: Grupo I (Controle), Grupo II (amido hidroxietílico) e Grupo III (Ringer lactato). Os animais do grupo II e III foram submetidos ao protocolo de hemodiluição com hematócrito alvo de 15%. A retirada de sangue foi realizada em 30 minutos e a expansão plasmática feita simultaneamente com amido hidroxietílico ou Ringer lactato nas proporções de 1:1 ou 1:3 em relação ao sangue retirado. Os parâmetros hemodinâmicos e de oxigenação, pH gástrico, ecocardiografia transesofágica (fração de ejeção através do método Simpson) foram coletados antes da hemodiluição (T0), no fim do procedimento de hemodiluição (T1) e após uma e duas horas (T2, T3). Os dados foram submetidos a análise de variância para medidas repetidas, seguida pelo teste Tukey e teste T student. Resultados: Em relação aos parâmetros do grupo controle, não houve diferença significante durante todo o procedimento. No grupo II e grupo III, houve aumento no índice cardíaco após hemodiluição (T0=5,80±1,46; T1=10,64±1,69 L.min-1.m2 e T0=5,53±1,18, T1=7,91±1,40 L.min-1.m2 respectivamente), e diminuição do índice de resistência vascular sistêmica (T0=1753±336, T1=822±140 dina.s.cm-5.m-2 e T0=1673±566, T1=1026±190 dina.s.cm-5.m-2 respectivamente), ambos estatisticamente significante. A fração de ejeção apresentou aumento significativo após a hemodiluição no grupo II. O pH gástrico diminuiu significativamente no grupo III. O lactato arterial aumentou de forma significante no grupo III após a hemodiluição. A microscopia eletrônica do ventrículo esquerdo mostraram discreta destruição de miofilamentos no grupo II. Houve destruição importante nas miofibrilas no grupo III. Conclusão: Estes resultados sugerem que na hemodiluição moderada a grave, o amido hidroxietílico consegue preservar melhor a estabilidade hemodinâmica do que a solução de Ringer lactato. / Normovolemic acute hemodilution is a procedure utilized to decrease the needs of blood transfusion during a variety of surgical procedures. Nevertheless, there are few works that evaluate its pulmonary effects as well as hemodynamic changes by means of echocardiography and tonometric evaluation. Methods: 23 anesthetized pigs (weight 46.6 ± 6.0 kg) were instrumented for standard hemodynamic monitoring. In order to prevent possible effects of inhaled anesthetics on pulmonary mechanics, intravenous anesthesia was chosen and consisted of ketamine, fentanyl and propofol administered throughout the study. Thirty minutes after anesthesia stabilization animals were randomized in three groups: Group I (Control), Group II (hydroxyethyl starch) and Group III (Lactated Ringer’s). Animals of group II and III were submitted to acute normovolemic hemodilution to reach a pre-established hematocrit around 15%. Blood withdrawal was accomplished in thirty minutes and plasma expansion was performed simultaneously with hydroxyethyl starch or Lactated Ringer’s administered in a proportion of 1:1 or 3:1 in relation to the amount of bloods withdrawn. Hemodynamic, gastric pH, transesophageal echography (ejection fraction, by Simpon method) and oxygen transport were measured before blood withdrawal (T0), at the end of hemodilution (T1), one and two hours after the end of hemodilution (T2, T3). Data were submitted to analysis of Variance for repeated measures followed by the Tukey test and also to a student T test. Results: In regard to all parameters of Group I (Control), there were no significant difference during the whole procedure. In Group II and Group III, there was an increase in cardiac index after hemodilution (T0=5.80±1.46; T1=10.64±1.69 L.min-1.m2 and T0=5.53±1.18, T1=7.91±1.40 L.min-1.m2), and a decrease in systemic vascular resistance index (T0=1753±336, T1=822±140 dyne.s.cm-5.m-2 and T0=1673±566, T1=1026±190 dyne.s.cm-5.m-2), both statistically significant. Ejection Fraction increased significantly after hemodilution in group II. Gastric pH decreased significantly in Group III, and arterial lactate increased significantly after hemodilution in group III. Electron microscopy of left ventricular bipsies showed a slight destruction in filament and preserved myofibrillar ultrastructure in group II. There was important destruction in myofibrillar ultrastructure in group III. Conclusion: These results suggest that in severe hemodilution, hydroxyethyl starch preserves hemonodynamic stability better than Lactate Ringer’s.

Le but de notre travail était d'étudier des nouveaux aspects de la physiopathologie et de la thérapeutique du choc anaphylactique chez le rat Brown Norway. La première partie de notre thèse étudie la physiopathologie systémique et régionale du choc anaphylactique. Le choc anaphylactique s'accompagne d'une diminution rapide du débit cardiaque, d'une altération brutale de l'autorégulation du débit sanguin cérébral et d'une atteinte respiratoire associant un oedème des voies respiratoires et un bronchospasme. La deuxième partie de notre travail s'intéresse à la prise en charge thérapeutique du choc anaphylactique. L'adrénaline s'avère supérieure à la vasopressine, pour inhiber le bronchospasme et diminuer la perméabilité microvasculaire, permettant une meilleure préservation de l'oxygénation cérébrale, en particulier dans la région de l'hippocampe, mais aussi une correction du bronchospsme et une diminution de l'hyperperméabilté bronchique à la phase précoce du choc anaphylactique. Nous avons également comparé les effets de trois types de solutés de remplissage administrés en association avec l'adrénaline au cours du choc anaphylactique, démontrant la supériorité de l'administration de soluté macromoléculaires tels que l'HES et l'échec des solutés salés hypertoniques. Enfin nous avons pu mettre en évidence l'intérêt de l'administration de bleu de méthylène (3mg/kg) en démontrant l'existence d'un effet synergique avec l'adrénaline au cours du choc anaphylactique / The aim of our work was to study new aspects of the pathophysiology and treatment of anaphylactic shock in the Brown Norway rat. The first part of this thesis focuses on the systemic and regional pathophysiology of anaphylactic shock which is accompanied by a rapid decrease in cardiac output, a sudden alteration of autoregulation of cerebral blood flow and a respiratory dysfunction involving swelling of the airways and bronchospasm. The second part of our work focuses on the therapeutic management of anaphylactic shock. Epinephrine was found to be superior to vasopressin, to inhibit bronchospasm and decrease microvascular permeability, allowing a better preservation of the cerebral oxygenation, in particular in the region of the hippocampus. Furthermore, it provided also an alleviation of bronchospasm and of bronchial hyperperméabilté in the early phase of anaphylactic shock. We also compared the effects of three types of fluid therapy administered in combination with adrenaline during anaphylactic shock, demonstrating the superiority of the administration of a macromolecular solution such as HES compared to hypertonic saline fluids. Finally we were able to highlight the usefulness of the administration of methylene blue (3mg/kg) demonstrating the existence of a synergistic effect with adrenaline during anaphylactic shock

Background Haemodilution and hypothermia induce coagulopathy separately, but their combined effect on coagulation has not been widely studied. Fibrinogen concentrate can correct dilutional coagulopathy and has an additional effect when combined with factor XIII concentrate. However, their effect on dilutional coagulopathy concomitant with hypothermia has not been studied previously. Free oscillation rheometry – FOR (Reorox®) – is a novel viscoelastic haemostatic assay that has not been studied in this context before. Methods Blood from 10 healthy volunteers was diluted by 33% with hydroxyethyl starch or Ringer’s acetate solutions. Effects of fibrinogen added in vitro with and without factor XIII were studied at 33°C and 37°C. Coagulation velocity (coagulation time) and clot strength (elasticity) were assessed with FOR. Coagulation was initiated in vitro with thromboplastin alone, or thromboplastin plus a platelet inhibitor. Results Hydroxyethyl starch increased the coagulation time and decreased clot strength significantly more than Ringer’s acetate solution, both in the presence and absence of a platelet inhibitor. There was a significant interaction between haemodilution with hydroxyethyl starch and hypothermia, resulting in increased coagulation time. After addition of fibrinogen, coagulation time shortened and elasticity increased, with the exception of fibrinogen-dependent clot strength (i.e., elasticity in the presence of a platelet inhibitor) after hydroxyethyl starch haemodilution. Factor XIII had an additional effect with fibrinogen on fibrinogen-dependent clot strength in blood diluted with Ringer’s acetate solution. Hypothermia did not influence any of the coagulation factor effects. Conclusions Both haemodilution and mild hypothermia impaired coagulation. Coagulopathy was more pronounced after haemodilution with hydroxyethyl starch than with Ringer’s acetate. Addition of fibrinogen with factor XIII was unable to reverse hydroxyethyl starch induced clot instability, but improved coagulation in blood diluted with Ringer’s acetate solution. Fibrinogen improved coagulation irrespective of hypothermia. / <p>Funding Agencies|Region Skane (Sweden)||CSL Beehring||</p>

Hydroxyethyl starches (HES) are the most routinely used synthetic colloids during fluid resuscitation and have reported effects on coagulation. The overall goal of the investigation in this thesis was to evaluate the effects of tetrastarch administration on hemodynamic, laboratory, and hemostatic variables in healthy dogs and dogs with systemic inflammation. The objectives were to compare hemodynamic and laboratory variables in dogs receiving an isotonic crystalloid (0.9% NaCl) or tetrastarch during health and after induction of systemic inflammation; to compare the hemostatic effects of an isotonic crystalloid (0.9% NaCl) and synthetic colloid (tetrastarch) in healthy dogs and dogs with induced systemic inflammation; to compare two different protocols for TEG® activation and to determine the correlation between TEG® variables and traditional coagulation test results. Sixteen adult purpose-bred Beagles were randomized into one of two groups receiving fluid resuscitation with either 40 mL/kg IV isotonic crystalloid (0.9% NaCl) or synthetic colloid (tetrastarch) after administration of lipopolysaccharide (LPS; 5 μg/kg, IV) or an equal volume of placebo (0.9% NaCl, IV). Blood samples, for analysis, were collected at 0, 1, 2, 4, and 24 hours from the time of fluid resuscitation. After a 14-day washout period, the study was repeated such that dogs received the opposite treatment (LPS or placebo) and the same resuscitation fluid. Resuscitation with equal volumes of 0.9% NaCl and tetrastarch caused similar changes in hemodynamic and laboratory variables in dogs with LPS-induced systemic inflammation; however, larger increases in HR and blood pressure were seen within the first 2 hours following tetrastarch administration compared to 0.9% NaCl. Tetrastarch administration increased COP in all dogs, despite a decrease in TS. Tetrastarch bolus administration to dogs with LPS-induced systemic inflammation also resulted in a transient hypocoagulability characterized by a prolonged PTT, decreased clot formation speed and clot strength, and acquired type 1 von Willebrand disease. Considering the limited additional benefit of tetrastarch administration on hemodynamic variables demonstrated, as well as the transient adverse hemostatic effects of tetrastarch administration, the increased cost associated with the use of tetrastarch likely negates its use as a first line treatment during fluid resuscitation in dogs. / Pet Trust Fund

Introdução: A Hemodiluição normovolêmica Aguda (HNA) envolve a retirada do sangue total e concomitante infusão de fluidos de reposição volêmica para manutenção da normovolemia. É uma estratégia que restringe a transfusão de sangue e evita a transmissão de doenças, imunossupressão e outras complicações associadas à transfusão sanguínea. Objetivos: O objetivo deste estudo foi determinar os efeitos de diversos fluidos na resposta inflamatória durante o procedimento de HNA. Métodos: Foram utilizados 28 suínos (n=28; 7/grupo) randomizados nos seguinte grupos: Controle, grupo anestesiado sem HNA; HNA + Amido, os animais foram submetidos a HNA sendo a reposição volêmica realizada com amido hidroxietílico 6% (130/0,4) na taxa de 1 ml de fluido para 1 ml de sangue retirado; HNA + NaCl, animais submetidos a HNA com reposição volêmica realizada com solução de cloerto de sódio 0,9% na proporção de 3:1; HNA + GEL, procedimento de HNA realizado com infusão da gelatina fluida modificada na taxa de 1:1. Os animais foram hemodiluídos durante 30 minutos para o hematócrito de 15%. Foram mensurados os parâmetros hemodinâmicos e foram coletados sangue para realização da hemogasometria e determinação dos níveis plasmáticos de IL-1b, TNF-a, IL-6 e IL-10, além do burst oxidativo de neutrófilos e monócitos circulantes. O lavado broncoalveolar foi coletado para mensuração dos níveis da IL-8 e do burst oxidativo de células pulmonares. O tecido pulmonar foi coletado para análise histológica e para imunoistoquímica para detecção da expressão de COX-2 e Eselectina. A análise estatística foi realizada por meio de provas paramétricas como a análise de variância com medidas repetidas (ANOVA), seguido do teste de Tukey- Kramer e de provas não paramétricas, o teste de Kruskal-Wallis. O grau de significância estabelecido foi de 5% (p < 0,05). Resultados: Os principais resultados deste estudo demonstraram que os animais hemodiluídos tanto com gelatina, como solução de cloreto de sódio 0,9% apresentaram resposta inflamatória mais pronunciada quando comparado aos outros grupos, traduzida no aumento de citocinas (TNF-, IL-6 e IL-10), na expressão de COX-2 e E-selectina no tecido pulmonar, além da observação de edema pulmonar, congestão e colapso alveolar. Apesar destes fatos, a resposta inflamatória estudada no sangue foi considerada de baixa magnitude. Conclusão: Durante a HNA, tanto a gelatina quanto a solução de cloreto de sódio 0,9% promove resposta inflamatória mais intensa quando comparada ao amido hidroxietílico 6% / Background: Acute normovolemic hemodilution (ANH) involves intentional withdrawal of the whole blood with concurrent infusion of fluids to maintain normovolemia. ANH avoids blood transfusion and deleterious effects related with transfusion. Objective: The aim of this study was to determine the effects of diverse fluids on the inflammatory response during ANH. Methods: Twenty-eight pigs (n=28; 7/group) were randomized as follows: (Control) control group without ANH; (ANH + HES) ANH with 6% hydroxyethyl starch at a ratio of 1:1; (ANH + NS) ANH with normal saline at a ratio of 3:1; (ANH + GEL) ANH with gelatin 1:1. Animals were hemodiluted to a hematocrit of 15% in 30 min. Hemodynamic parameters were recorded, and blood samples were collected to determine plasma levels of IL-1, IL-6, TNF-, IL-10, as well as gas analysis. IL-8 was measured in the bronchoalveolar lavage fluid (BALF). Neutrophil and macrophage oxidative burst activity were determined in the peripheral blood and BALF. Histophatological and immunohistochemistry to COX-2 and E-selectin expression were performed with the lung tissue. Data were submitted to analysis of Variance for repeated measures followed by the Tukey-Kramer test. To immunohistochemistry and histophatological scores the Kruskal-Wallis test was used to assess the significance. The p < 0.05 was considered significant. Results: The principal findings of this investigation showed that animals hemodiluted with GEL and NS had a more pronounced inflammatory response when compared to those hemodiluted with HES. The animals in the GEL and NS groups showed an increase in cytokines (TNF-, IL-6, IL-10), a strong expression of COX-2 and Eselectin in the lung tissue and pulmonary edema, congestion and alveoli collapse. However, the magnitude of this response was quite small showing that ANH does not substantially activate the inflammatory system. Conclusion: During ANH, GEL and NS but not HES could elicit an inflammatory response besides the effective plasma volume therapy

Introdução: A Hemodiluição normovolêmica Aguda (HNA) envolve a retirada do sangue total e concomitante infusão de fluidos de reposição volêmica para manutenção da normovolemia. É uma estratégia que restringe a transfusão de sangue e evita a transmissão de doenças, imunossupressão e outras complicações associadas à transfusão sanguínea. Objetivos: O objetivo deste estudo foi determinar os efeitos de diversos fluidos na resposta inflamatória durante o procedimento de HNA. Métodos: Foram utilizados 28 suínos (n=28; 7/grupo) randomizados nos seguinte grupos: Controle, grupo anestesiado sem HNA; HNA + Amido, os animais foram submetidos a HNA sendo a reposição volêmica realizada com amido hidroxietílico 6% (130/0,4) na taxa de 1 ml de fluido para 1 ml de sangue retirado; HNA + NaCl, animais submetidos a HNA com reposição volêmica realizada com solução de cloerto de sódio 0,9% na proporção de 3:1; HNA + GEL, procedimento de HNA realizado com infusão da gelatina fluida modificada na taxa de 1:1. Os animais foram hemodiluídos durante 30 minutos para o hematócrito de 15%. Foram mensurados os parâmetros hemodinâmicos e foram coletados sangue para realização da hemogasometria e determinação dos níveis plasmáticos de IL-1b, TNF-a, IL-6 e IL-10, além do burst oxidativo de neutrófilos e monócitos circulantes. O lavado broncoalveolar foi coletado para mensuração dos níveis da IL-8 e do burst oxidativo de células pulmonares. O tecido pulmonar foi coletado para análise histológica e para imunoistoquímica para detecção da expressão de COX-2 e Eselectina. A análise estatística foi realizada por meio de provas paramétricas como a análise de variância com medidas repetidas (ANOVA), seguido do teste de Tukey- Kramer e de provas não paramétricas, o teste de Kruskal-Wallis. O grau de significância estabelecido foi de 5% (p < 0,05). Resultados: Os principais resultados deste estudo demonstraram que os animais hemodiluídos tanto com gelatina, como solução de cloreto de sódio 0,9% apresentaram resposta inflamatória mais pronunciada quando comparado aos outros grupos, traduzida no aumento de citocinas (TNF-, IL-6 e IL-10), na expressão de COX-2 e E-selectina no tecido pulmonar, além da observação de edema pulmonar, congestão e colapso alveolar. Apesar destes fatos, a resposta inflamatória estudada no sangue foi considerada de baixa magnitude. Conclusão: Durante a HNA, tanto a gelatina quanto a solução de cloreto de sódio 0,9% promove resposta inflamatória mais intensa quando comparada ao amido hidroxietílico 6% / Background: Acute normovolemic hemodilution (ANH) involves intentional withdrawal of the whole blood with concurrent infusion of fluids to maintain normovolemia. ANH avoids blood transfusion and deleterious effects related with transfusion. Objective: The aim of this study was to determine the effects of diverse fluids on the inflammatory response during ANH. Methods: Twenty-eight pigs (n=28; 7/group) were randomized as follows: (Control) control group without ANH; (ANH + HES) ANH with 6% hydroxyethyl starch at a ratio of 1:1; (ANH + NS) ANH with normal saline at a ratio of 3:1; (ANH + GEL) ANH with gelatin 1:1. Animals were hemodiluted to a hematocrit of 15% in 30 min. Hemodynamic parameters were recorded, and blood samples were collected to determine plasma levels of IL-1, IL-6, TNF-, IL-10, as well as gas analysis. IL-8 was measured in the bronchoalveolar lavage fluid (BALF). Neutrophil and macrophage oxidative burst activity were determined in the peripheral blood and BALF. Histophatological and immunohistochemistry to COX-2 and E-selectin expression were performed with the lung tissue. Data were submitted to analysis of Variance for repeated measures followed by the Tukey-Kramer test. To immunohistochemistry and histophatological scores the Kruskal-Wallis test was used to assess the significance. The p < 0.05 was considered significant. Results: The principal findings of this investigation showed that animals hemodiluted with GEL and NS had a more pronounced inflammatory response when compared to those hemodiluted with HES. The animals in the GEL and NS groups showed an increase in cytokines (TNF-, IL-6, IL-10), a strong expression of COX-2 and Eselectin in the lung tissue and pulmonary edema, congestion and alveoli collapse. However, the magnitude of this response was quite small showing that ANH does not substantially activate the inflammatory system. Conclusion: During ANH, GEL and NS but not HES could elicit an inflammatory response besides the effective plasma volume therapy

Introdução: A hemodiluição normovolêmica aguda (HNA) é estratégia utilizada para diminuir a necessidade de transfusão em procedimentos cirúrgicos. O hematócrito alvo, a solução empregada e os riscos da HNA são controversos e, embora as ações sobre os sistemas nervoso e cardiocirculatório tenham sido extensamente pesquisados, há poucos estudos sobre implicações pulmonares da HNA. O objetivo deste estudo é avaliar os efeitos pulmonares da HNA comparando amido hidroxietílico e Ringer lactato. Métodos: Vinte e cinco porcos foram monitorizados e cateterizados. Utlizou-se anestesia intravenosa contínua com propofol, cetamina, fentanil e pancurônio. Após estabilização da anestesia, os animais foram randomizados: Grupo Controle (n=8), Grupo HES (amido hidroxietílico, n=7) e Grupo RL (Ringer lactato, n=10). Os animais dos grupos II e III foram submetidos a HNA até hematócrito pré-estabelecido de 15%. A retirada do sangue foi acompanhada da expansão plasmática com amido hidroxietílico ou Ringer lactato na proporção de 1:1 ou 3:1 respectivamente. Medidas de mecânica respiratória e oxigenação sangüínea foram realizadas antes da retirada de sangue (T0), ao término da hemodiluição (T1) e após uma e duas horas (T2 e T3). Ao final foram realizadas biópsias pulmonares. Os dados foram submetidos à análise de variância para medidas repetidas (ANOVA) seguidas pelo teste de Tukey. Resultados: Em relação aos parâmetros do grupo controle, não houve diferença significante durante todo o procedimento. O grupo Ringer lactato demonstrou diminuição da complacência estática e aumento da diferença alvéolo-arterial de O2 (DAa-O2) em relação ao controle (*P<0,05). A análise histopatológica evidenciou atelectasias e alargamento da membrana basal na barreira alvéolo-capilar no grupo Ringer lactato. O grupo amido hidroxietílico apresentou comportamento semelhante ao grupo controle. Conclusões: O estudo sugere que na HNA acentuada, o amido hidroxietílico é superior na preservação estrutural do pulmão, evidenciado pormanter a complacência pulmonar e a oxigenação, quando comparada à realizada com solução de Ringer lactato / Introduction: Acute normovolemic hemodilution (ANH) is a common procedure to decrease the needs of blood transfusion during a variety of surgical procedures. There are controversies regarding ANH such as the target hematocrit, the solution to be used and its risks. Although its effects in heart and brain have been extensively studied; investigations concerning its pulmonary effects are lacking. The aim of this experiment was to compare the pulmonary effects of ANH with hydroxyethyl starch and lactated Ringer\'s. Methods: Twenty five pigs were instrumented for standard hemodynamic monitoring. Intravenous anesthesia consisted continuous infusion of propofol, ketamine, fentanyl and pancuronium. After anesthesia stabilization animals were randomized: Control group (n=8), HES group (hydroxyethyl starch, n=7) and LR group (lactated Ringer\'s, n=10). Animals of Control Group were anesthetized and observed. Group Animals of group HES and LR were submitted to ANH to reach a pre-established hematocrit around 15%. Blood withdrawal was accomplished simultaneously with plasma expansion performed with hydroxyethyl starch (1:1) or with lactated Ringer\'s (3:1). Pulmonary mechanics and oxygen transport and were measured before blood withdrawal (T0), at the end of hemodilution (T1), and one and two hours after the end of the hemodilution (T2, T3). Lungs biopsies were performed at the end. Data were submitted to analysis of Variance for repeated measures followed by the Tukey test. Results: In regard to all parameters of Control group, there were no significant differences during the whole procedure. The LR group demonstrated a decrease in compliance and an increased in (a-A)DO2 (*P<0,05). Hystopathological lung analysis revealed moderate to serious collapses as well as basement membrane enlargement in group LR. The HES data were similar to that found in control group. Conclusion: These results suggest that in severe ANH, HES preserves pulmonary structure and seems to less interfere with pulmonary mechanics and oxygenation indexes when compared to lactated Ringer\'s

Introdução: A hemodiluição normovolêmica aguda (HNA) é estratégia utilizada para diminuir a necessidade de transfusão em procedimentos cirúrgicos. O hematócrito alvo, a solução empregada e os riscos da HNA são controversos e, embora as ações sobre os sistemas nervoso e cardiocirculatório tenham sido extensamente pesquisados, há poucos estudos sobre implicações pulmonares da HNA. O objetivo deste estudo é avaliar os efeitos pulmonares da HNA comparando amido hidroxietílico e Ringer lactato. Métodos: Vinte e cinco porcos foram monitorizados e cateterizados. Utlizou-se anestesia intravenosa contínua com propofol, cetamina, fentanil e pancurônio. Após estabilização da anestesia, os animais foram randomizados: Grupo Controle (n=8), Grupo HES (amido hidroxietílico, n=7) e Grupo RL (Ringer lactato, n=10). Os animais dos grupos II e III foram submetidos a HNA até hematócrito pré-estabelecido de 15%. A retirada do sangue foi acompanhada da expansão plasmática com amido hidroxietílico ou Ringer lactato na proporção de 1:1 ou 3:1 respectivamente. Medidas de mecânica respiratória e oxigenação sangüínea foram realizadas antes da retirada de sangue (T0), ao término da hemodiluição (T1) e após uma e duas horas (T2 e T3). Ao final foram realizadas biópsias pulmonares. Os dados foram submetidos à análise de variância para medidas repetidas (ANOVA) seguidas pelo teste de Tukey. Resultados: Em relação aos parâmetros do grupo controle, não houve diferença significante durante todo o procedimento. O grupo Ringer lactato demonstrou diminuição da complacência estática e aumento da diferença alvéolo-arterial de O2 (DAa-O2) em relação ao controle (*P<0,05). A análise histopatológica evidenciou atelectasias e alargamento da membrana basal na barreira alvéolo-capilar no grupo Ringer lactato. O grupo amido hidroxietílico apresentou comportamento semelhante ao grupo controle. Conclusões: O estudo sugere que na HNA acentuada, o amido hidroxietílico é superior na preservação estrutural do pulmão, evidenciado pormanter a complacência pulmonar e a oxigenação, quando comparada à realizada com solução de Ringer lactato / Introduction: Acute normovolemic hemodilution (ANH) is a common procedure to decrease the needs of blood transfusion during a variety of surgical procedures. There are controversies regarding ANH such as the target hematocrit, the solution to be used and its risks. Although its effects in heart and brain have been extensively studied; investigations concerning its pulmonary effects are lacking. The aim of this experiment was to compare the pulmonary effects of ANH with hydroxyethyl starch and lactated Ringer\'s. Methods: Twenty five pigs were instrumented for standard hemodynamic monitoring. Intravenous anesthesia consisted continuous infusion of propofol, ketamine, fentanyl and pancuronium. After anesthesia stabilization animals were randomized: Control group (n=8), HES group (hydroxyethyl starch, n=7) and LR group (lactated Ringer\'s, n=10). Animals of Control Group were anesthetized and observed. Group Animals of group HES and LR were submitted to ANH to reach a pre-established hematocrit around 15%. Blood withdrawal was accomplished simultaneously with plasma expansion performed with hydroxyethyl starch (1:1) or with lactated Ringer\'s (3:1). Pulmonary mechanics and oxygen transport and were measured before blood withdrawal (T0), at the end of hemodilution (T1), and one and two hours after the end of the hemodilution (T2, T3). Lungs biopsies were performed at the end. Data were submitted to analysis of Variance for repeated measures followed by the Tukey test. Results: In regard to all parameters of Control group, there were no significant differences during the whole procedure. The LR group demonstrated a decrease in compliance and an increased in (a-A)DO2 (*P<0,05). Hystopathological lung analysis revealed moderate to serious collapses as well as basement membrane enlargement in group LR. The HES data were similar to that found in control group. Conclusion: These results suggest that in severe ANH, HES preserves pulmonary structure and seems to less interfere with pulmonary mechanics and oxygenation indexes when compared to lactated Ringer\'s