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Conclusions 1. In comparison to the Ringer‘s acetate solution the use of HyperHaes® solution after coronary artery bypass surgery had positive effect on haemodynamic parameters: cardiac index increased (p<0.05), systolic volume index increased (p<0.05), cardiac afterload decreased, that is pulmonary vascular resistance index decreased (p<0.05) and systemic vascular resistance index decreased (p<0.05); the difference between the central and peripheral temperatures in experimental group (p<0.05). 2. The oxygen transport was more effective (oxygen delivery index increased (p<0.05)) when HyperHaes® solution was used in comparison to Ringer‘s acetate solution. 3. No substantial effect of HyperHaes® solution on the duration of artificial lung ventilation and intrapulmonary shunt size was defined. 4. The use of HyperHaes® solution influenced substantially some parameters of homeostasis (serum sodium concentration increased (p<0.05), serum potassium concentration decreased (p<0.05)) in compa-rison to Ringer‘s acetate solution. 5. Higher diuresis (p<0.01), lower need for the infusion therapy for the first 24 hours (p<0.05), lower total fluid balance (p<0.01) were determined in HyperHaes® group versus Ringer‘s acetate group. 6. No adverse effects (disturbances of homeostasis, neurologic symptoms, increased bleeding through mediastinal tubes, anaphylactic reactions) were noted in patients who received HyperHaes® solution.

Hypertonic saline (HS) is an accepted treatment for traumatic brain injury (TBI). However, the behavioral and cognitive consequences following HS administration have not thoroughly been examined. Recent preclinical evidence has suggested that nicotinamide (NAM) is beneficial for recovery of function following TBI. The first study compared the behavioral and cognitive consequences of HS and NAM as competitive therapeutic agents for the treatment of TBI. Following controlled cortical impact (CCI), bolus administrations of NAM (500 mg/kg), 7.5% HS, or 0.9% saline vehicle (1.0 mL/kg) were given at 2, 24, and 48 hrs post-CCI. Behavioral results revealed that animals treated with NAM and HS showed significant improvements in beam walk and locomotor placing compared to the Vehicle group. The Morris water maze (MWM) retrograde amnesia test was conducted on day 12 post-CCI and showed that all groups had significant retention of memory compared to injured, Vehicle-treated animals. Working memory was also assessed on days 18-20 using the MWM. The NAM and Vehicle groups quickly acquired the task; however, HS animals showed no acquisition of this task. Histological examinations revealed that the HS-treated animals lost significantly more cortical tissue than either the NAM or Vehicle-treated animals. HS-treated animals showed a greater loss of hippocampal tissue compared to the other groups. In general, NAM showed a faster rate of recovery than HS without this associated tissue loss. Study 1 suggested that future research into HS should include drug injection time course studies. Multiple injections may be responsible for the notable tissue damage. Therefore, it is possible that fewer injections will result in comparable behavioral recovery and less tissue damage that was observed. Due to the detrimental effects of 7.5% HS on cognition and hippocampal tissue following multiple administration in study 1, the proposed second study sought to study the behavioral and cognitive effects of HS using either single or multiple injection regime. The proposed study entailed a lengthier testing schedule than in study 1 and included the same histological examination to compare the different dosages. Additionally, edema formation was measured 24 hours following each drug endpoint in order to delineate the possible underlying mechanism of the observed deficits. In Study 2, HS tended to improve function on motor, sensorimotor and neurological tasks. Although this was a trend on all tests, animals treated with a single administration of HS overall performed better on all tasks compared to those receiving double or multiple injections. In the retrograde amnesia test, although not significant, the Sham, HS-2, and HS-24 animals showed improvement; whereas, the Vehicle and HS-48 animals showed no improvement in performance. This could possibly be linked to the additional hippocampal tissue loss that was noted in the HS-48 animals. In the working memory paradigm, the HS-2 and Vehicle groups had longer latencies to reach the platform than did the Sham group. However, after the first testing day, there were no significant differences between any of the groups. All animals treated with HS performed at the same rate and their performance either stayed the same over the three day testing period or became worse. It appears these animals were unable to learn and improve in the new memory acquisition task which is comparable to the results found in study 1. In study 1, there were again no observed hippocampal volume differences between the Sham and Vehicle-treated animals. However, there was extensive hippocampal tissue damage observed in all of the HS groups. Furthermore, animals treated with a single administration of HS had less hippocampal loss than those with double or multiple doses. Those animals receiving more than one dose of HS lost significantly more hippocampal tissue than the Vehicle group. The results of study 2 are comparable, and support, the results of study 1. Both studies support the strengths and weakness of HS therapy following TBI. Although there are potential benefits of HS therapy, there are also detrimental risks involved. Cognitive and structural damage could possible occur if the dosage amounts are not closely studied and monitored. Although the use of HS may be beneficial to reduce ICP following TBI, it appears that the use of HS may also lead to direct or indirect tissue loss possibly by chronic cellular dehydration. Stronger or more delineated effects may be noticed using higher doses or concentrations of HS in future studies. However, due to the nature of these results, caution should be advised with the use of all therapeutic usage of HS until further detailed studies are conducted.

Orientador: Artur Udelsmann / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T15:05:32Z (GMT). No. of bitstreams: 1 Bonfim_MatheusRodrigues_M.pdf: 2022340 bytes, checksum: a5de652e3794240a34fc70fa9e5da209 (MD5) Previous issue date: 2008 / Resumo: Justificativa e objetivos: Várias soluções podem ser empregadas no tratamento da hipovolemia, sendo as mais comuns as cristalóides e as colóides. Na década de 1980, estudou-se o uso de soluções salinas hipertônicas, na reposição volêmica com pequenos volumes. Posteriormente foi indicada a associação das soluções hipertônicas com soluções colóides com resultados satisfatórios. O hidroxi-etil amido hipertônico é uma nova solução de reposição volêmica, composta por um colóide associado ao NaCl 7,2%. O objetivo deste trabalho foi estudar, em cães submetidos à hipovolemia, as respostas hemodinâmicas da reposição volêmica com solução fisiológica e hidroxi-etil amido hipertônico. Método: 40 cães sob anestesia geral e monitorização hemodinâmica com pressão arterial invasiva e cateter de Swan-Ganz, após medidas hemodinâmicas em repouso, foram sangrados 20 ml.kg-1 em 10 minutos e tiveram os parâmetros novamente medidos após 10 minutos; em seguida foi realizada reposição volêmica com solução fisiológica na razão de duas vezes o volume retirado em 5 minutos ou 4 ml.kg-1 de hidroxi-etil amido hipertônico também em 5 minutos e os dados hemodinâmicos foram medidos após 5, 15, 30, 45 e 60 minutos. Os resultados foram comparados estatisticamente. Resultados: nesse estudo, a reposição volêmica com as duas soluções fez os valores retornarem a níveis hemodinâmicos satisfatórios. Valores iniciais maiores foram observados com a solução fisiológica, mas tenderam a diminuir progressivamente, com o hidroxi-etil amido hipertônico os parâmetros estudados retornaram a valores semelhantes ao repouso e variaram menos. O índice cardíaco mostrou valores maiores para o grupo SF em todos os momentos após a reposição volêmica (p<0,001) . As pressões arteriais e pulmonares não mostraram diferenças entre os grupos. As pressões capilar pulmonar e venosa central mostraram valores maiores para o grupo SF imediatamente após a reposição volêmica (M3). Conclusões: ambas as soluções se mostraram eficientes na reposição volêmica no curto prazo estudado, mas o hidroxi-etil amido hipertônico proporcionou resultados mais estáveis. Unitermos: hipovolemia, hidroxi-etil amido, solução salina hipertônica / Abstract: Background and Objectives: Several solutions may be employed for the treatment of hypovolemia. Among the various solutions used, the most common are crystalloids and colloids. In the 80s, the use of hypertonic saline solutions was studied for small-volume fluid replacement. Subsequently, these hypertonic solutions were associated with colloid solutions producing satisfactory results. Hypertonic hydroxyethyl starch is a new solution used for volume replacement that is composed of a colloid associated with 7.2% NaCl. The purpose of this study was to examine hemodynamic response to volume replacement using saline solution and hypertonic hydroxyethyl starch in dogs subjected to hypovolemia. Method: Forty (40) dogs underwent general anesthesia and were hemodynamically monitored with intra-arterial blood pressure monitoring and a Swan-Ganz catheter. Baseline hemodynamic values were measured and the dogs were bled 20 ml.Kg.1 Parameters were measured after 10 minutes. Volume replacement with saline solution was then performed at a ratio of twice the volume removed or 4 ml.Kg-1 of hypertonic hydroxyethyl starch. Hemodynamic data was measured after 5, 15, 30, 45 and 60 minutes. The results were statistically compared. Results: In this study, values returned to satisfactory hemodynamic levels when volume was replaced with both solutions. Higher initial values were observed when saline solution was used. However, these values tended to decrease progressively. When hypertonic hydroxyethyl starch was used, the parameters studied returned more rapidly to values similar to those at baseline and less variation was observed. The cardiac index showed higher values for the saline group at all time periods studied after volume replacement (p<0.001). Arterial blood pressure and pulmonary blood pressure showed no differences between groups. Pulmonary capillary pressure and central venous pressure showed higher values for the saline group immediately after volume replacement (M3). Conclusions: Both solutions proved to be efficient at replacing volume in the short period studied. However, hypertonic hidroxyethyl starch provided more stable results. Uniterms: Hypovolemia, Hetastarch, Saline Solution, Hypertonic / Mestrado / Cirurgia / Mestre em Cirurgia

A hemodiluição normovolêmica aguda (HNA) é terapia mundialmente reconhecida como vantajosa em cirurgias que possuem grande potencial para sangramento, mas o edema provocado pela maior infusão de fluidos pode ser danoso em alguns pacientes. No intuito de avaliar as repercussões hemodinâmicas e laboratoriais da utilização da solução salina hipertônica a 7,5% como líquido parcial de reposição na HNA foram estudados 20 pacientes submetidos à artrodese para correção de escoliose de coluna. No grupo 1 (SS 0,9%, n=10) o sangue retirado na HNA, realizada momentos antes da cirurgia, foi reposto por solução salina 0,9% em um volume três vezes maior que o retirado. No grupo 2 (SS 7,5%, n=10) a metade do que foi retirado foi reposto com solução a 0,9% (três vezes o volume retirado) e a outra metade por 4 ml.kg-1 de solução salina hipertônica 7,5%. Nenhum dos pacientes apresentou distúrbios do equilíbrio ácido-básico e as alterações metabólicas (aumento da osmolaridade, sódio e cloro plasmáticos) foram passageiras. Os pacientes mantiveram-se hemodinamicamente estáveis e não foi observado sangramento anormal intra-operatório. A incidência de transfusão sangüínea foi semelhante embora os pacientes do grupo solução hipertônica tenham ficado clinicamente menos edemaciados. Mesmo não sendo objeto do estudo, observou-se menor incidência de infecções pós-operatórias nos pacientes submetidos à infusão de solução hipertônica, o que pode significar potencial efeito protetor da solução. Embora mais estudos com números maiores de pacientes sejam necessários para se comprovar esses efeitos, a solução hipertônica mostrou-se barata, simples e segura como maneira de redução do volume infundido na HNA. / The acute normovolemic hemodilution (ANH) is a therapy recognized as benefic in surgeries that have a great potential for bleeding but the swelling caused by solutions infused intra-operative can be harmful in some kind of patients. Twenty patients submitted to arthrodesis for scoliosis correction were studied in order to evaluate the hemodynamic and laboratory effects of 7.5% hypertonic saline solution as a partial fluid replacement in ANH. In group 1 (SS 0.9%, n = 10) the collected blood in ANH was replaced by saline solution 0.9% in a volume three times greater than the withdrawal. In group 2 (SS 7.5%, n = 10), half of the blood removed was restored by 0.9% solution (three times the amount withdrawn) and the other half by 4 ml.kg-1 of 7.5% solution. None of the patients presented acid-base disorders. Metabolic changes - enhanced of plasmatic levels of sodium, chlorine and osmolarity - were all transitory. Patients remain hemodynamic stable and no abnormal bleeding was observed. They had similar incidence of blood transfusion but the ones in hypertonic solution group were clinically less swollen. Lower incidences of post-operative infections were found in this group, which could mean a possible protector potential of hypertonic solution. SS 7.5% was a cheap, simple and safe alternative to reduce volume infused in ANH.

Japanese eels (Anguilla japonicas) are snakelike fishes living in waters in the Asian region. In contrast to most fishes which are stenohalines that can only live in waters with a narrow range of salinity, Japanese eels are classified as euryhalines that can habitat in a broad range of salinity. As the lifecycle of Japanese eels consists of stages across fresh and seawater districts, a well-developed osmoregulation mechanism is needed to balance the intra- and extra- cellular osmolarity of the fishes throughout the seawater acclimation process. While fish gills are one of the organs that separating the ambient water and the inner body fluid of the fish, the fish gills of the Japanese eels have been studied as one of the most crucial organs for osmoregulation purposes. Yet, the osmoregulation and survival strategies of Japanese eels under hyperosmotic stress has not been fully elucidated. In chapter 2, this study has performed a transcriptome study on the ex vivo gill filament model of the Japanese eel to profile the molecular responses after a hypertonic treatment of 4 hours or 8 hours. The experiment is aimed to mimic the gill cells exposed to seawater in the seawater acclimation process of Japanese eels. A profile of differential expressed genes (DEGs) has been revealed that 577 DEGs were commonly upregulated and 711 DEGs were commonly downregulated in both 4- and 8-hours hypertonic treatment. Functional analysis and annotation have been processed with these DEGs, including Ingenuity Canonical Pathways analysis and gene ontology. These analyses have revealed that the cellular homeostasis of the gill cells has been disrupted and cell death responses has been induced by osmotic stress. The results have raises a concern that the maintenance of cellular viability and a cell death regulation mechanism are needed for the fishes to survive in the early stage of seawater acclimation. In chapter 3, this chapter demonstrated that gill cells in Japanese eels are susceptible to apoptosis when they are exposed to hyperosmotic treatments in both in vitro gill cell and the ex vivo gill filament model. To maintain the viability of the gills cells, two inhibitors of apoptosis, XIAP, and survivin, were seen to be expressed in gills cells. The expression of XIAP and survivin were upregulated by dexamethasone, which is an agonist mimicking the effect of cortisol on fishes in seawater acclimation. Meanwhile, the expression levels of the apoptosis executor, caspase 3, were downregulated. These data suggested that with the regulation of cortisol express in the fishes, XIAP and survivin are effective apoptosis regulators in the gill cells of Japanese eels. The study has demonstrated the molecular responses of the gills of Japanese eels exposed to hyperosmotic stress at the transcriptional level and post-translational level by using transcriptome studies and protein study respectively. The study has paved cell death regulation to be another the key field to study in understanding the ability of salinity tolerance in euryhalines.

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Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

O presente estudo visou avaliar a influência da diabetes experimental no perfil nociceptivo orofacial de ratos. Foram utilizados 40 ratos Wistar, no qual 20 receberam injeção de estreptozotocina (STZ) para a indução da diabetes experimental (grupo diabetes), e 20 receberam solução de citrato de sódio (CS - grupo controle). Esses animais foram subdivididos em dois subgrupos de 10 ratos que apenas se diferenciaram com relação à substância que foi injetada no músculo masseter: solução salina isotônica (SI) [n=10: Cont-SI; n=10: Diab-SI] ou hipertônica (SH) [n=10: Cont-SH; n=10: Diab-SH]. Num primeiro momento foi feita a administração intraperitoneal de STZ ou CS e quatorze dias após, com os animais levemente anestesiados, foi realizada a injeção de 100 &#x3BC;L de solução SH-5% ou SI-0,9% na região média do músculo masseter esquerdo, numa profundidade de 5 mm e então foi quantificado, por dois minutos, o comportamento nociceptivo caracterizado pelo ato do rato sacudir/agitar a pata posterior ipsilateral o que é aceito como índice de nocicepção muscular. Uma hora após a avaliação comportamental nociceptiva, os ratos foram eutanasiados por sobredose de anestésico e o músculo masseter esquerdo foi retirado com auxílio de um bisturi circular; parte deste músculo foi utilizada para a análise da expressão de RNA para as citocinas pró inflamatórias [fator de necrose tumoral (TNF&#x3B1;), IL1&#x3B2;, IL6, ciclooxigenase 2 (COX-2)] e anti inflamatórias [IL- 2, IL- 10)] por meio da técnica de Reação em Cadeia da Polimerase quantitativa (qPCR); a parte restante foi corada pela técnica de hematoxilina-eosina e depois realizada a análise histopatológica descritiva em microscópio de luz. Foi observado um aumento significativo do comportamento nociceptivo nos ratos não diabéticos ou normoglicêmicos submetidos à injeção de SH (Cont-SH) em relação aos demais grupos que foram similares entre si. Na análise de citocinas, verificamos que o músculo masseter de ratos não diabéticos submetidos à injeção de SH (Cont-SH) apresentaram um aumento significativo da expressão relativa de TNF&#x3B1; em relação aos demais grupos que foram similares entre si; para a IL-1&#x3B2; também foi verificada um aumento da expressão relativa do grupo (Cont-SH) em relação aos grupos Cont-SI e Diab-SI, mas não em relação ao grupo Diab-SH e a IL-6 foi significativamente mais expressa no músculo masseter de ratos não diabéticos submetidos à injeção de SH em relação ao grupo Cont-SI, mas não foi diferente nos demais grupos. As demais citocinas avaliadas (COX-2, IL-2 e IL-10) não mostraram diferenças significativas entre os grupos. Na análise histopatológica não foram identificadas alterações significativas no tecido muscular, apenas um discreto infiltrado inflamatório no grupo Cont-SH. Diante dos resultados obtidos, podemos concluir que os ratos diabéticos apresentaram um reduzido comportamento nociceptivo, o que indica uma hiponocicepção química. / This study aimed to evaluate the influence of experimental diabetes in rats nociceptive orofacial profile. 40 Wistar rats were used, in which 20 received streptozotocin injection (STZ) to induce experimental diabetes (group), and 20 received sodium citrate solution (CS - control group). These animals were divided into two groups of 10 rats differed only with respect to the substance that has been injected into the masseter: isotonic saline (IS) [n = 10: Cont-IS; n = 10: Diab-IS] or hypertonic (HS) [n = 10: Cont-HS; n = 10: Diab-HS]. Initially was taken intraperitoneal administration of STZ or CS and fourteen days with lightly anesthetized animal, injection of 100 &#x3BC;L of 5% HS solution or 0.9% IS in the middle region of the left masseter muscle was performed at a depth of 5 mm and then was quantified for two minutes, the nociceptive behavior characterized by the rats act shake/agitating the ipsilateral hind paw which is accepted as muscle nociception index. One hour after the nociceptive behavioral evaluation, the rats were euthanized by overdose of anesthetic and the left masseter muscle was removed with the aid of a circular scalpel; part of this muscle was used for analysis of RNA expression for pro - inflammatory cytokines [tumor necrosis factor (TNF), IL1&#x3B2;, IL6, cyclooxygenase 2 (COX-2)], and anti - inflammatory [IL-2, IL - 10] by reaction technique of quantitative polymerase chain (qPCR); the remaining half was stained with hematoxylin-eosin and then conducted a descriptive histopathological analysis by light microscopy. It was observed a significant increase of nociceptive behavior in non-diabetic and normoglycemic rats with injection of HS (Cont-HS) compared to other groups that were similar to each other. In cytokine analysis, we find that the masseter muscle of non-diabetic rats with injection of (Cont-HS) showed a significant increase in TNF relative expression compared to the other groups that were similar to each other; for IL-1&#x3B2; was also found an increase of the group relative expression (Cont-HS) with respect to Cont-IS and Diab-IS groups, but not in relation to Diab-HS group and IL-6 was significantly expressed the masseter muscle of rats without diabetes underwent injection compared to Cont-IS group, but was not different in the other groups. On the evaluated cytokines (COX-2, IL-2 and IL-10) showed no significant differences between groups. Histologically significant changes were not found in muscle tissue, just a mild inflammatory infiltrate in the Cont-SH group. Based on these results, we conclude that the diabetic rats had a reduced nociceptive behavior, which indicates a chemical hyponociception.