In this thesis, we included results from two studies. The first one considered the effects of the blood volume changes, during blood donation, on the heart rate variability (HRV) measured, non-invasively, form electrocardiographic (ECG) and photoplethysmographic (PPG) signals. Our results showed that, during blood donation, there were no significant changes in the pulsatile area of PPG signal, while heart rate increased. No significant changes were noticed in HRV extracted from both signals. Error analysis between the HRV extracted from ECG and peak interval variability (PIV) suggested that the error during blood donation was increased which means that the use of PIV extracted from PPG signal, used as a replacement diagnostic tool in clinical applications, needs further investigations and should be carefully studied in non-stationary cardiovascular situations such as blood donation. The imbalance between the two branches of the autonomic nervous system, sympathetic and parasympathetic, vagal, may result in a harmful activation of myocardial tissues which cause arrhythmias and sudden cardiac death. Although the study of the sympathovagal balance have been attracting many researchers, further studies are needed to elucidate the effects of many kinds of drugs on the autonomic modulation of the cardiac muscle, specifically, the cells of sinoatrial (SA) node. The aim of the second part of this thesis was to assess the effects of calcium channel blocker (Verapamil), calcium channel sensitizer (Levosimendan), calcium chloride (CaCl2), the combinations of verapamil/ CaCl2, levosimendan/ CaCl2, and noradrenaline infusion on beat-to-beat cardiovascular variability represented, in this research, by systolic blood pressure variability (SBPV), and stroke volume variability (SVV) signals. We used Fat Fourier Transform (FFT) to evaluate the power spectral density of the fluctuations in both signals to evaluate the effects of short-term treatments with those drugs on the sympathovagal balance in normal rats. Then, we compared the spectra obtained from SBPV and SVV to decide which of these fluctuations along with corresponding spectrum was more able to provide a clear feedback about the autonomic nervous system. Our data suggests that there were a significant correlations between low- (LF), mid- (MF), and high-frequency (HF) spectra obtained from SBPV and SVV except between the HF spectra estimated from after the infusion of levosimendan where a poor correlation (r = 0.530, p = 0.281) was noticed. This that both HF components obtained provide different information regarding the autonomic nervous system modulation of the SA node cells, while the results obtained from the rest of experiments showed that both signals provide same information about the modulation of sympathetic and parasympathetic tone due to all stages of different drugs infusion studied in this thesis. Besides that, we found that both spectra may be used to track the fluctuations in the cardiac output as a result of the drugs infusion.

Kohlenmonoxid (CO) wird nach Einatmung weitgehend an Hämoglobin gebunden, eine minimale Bindung findet auch an Myoglobin statt. Die Kohlenmonoxid-Hämoglobinkonzentration (COHb) im Blut steigt nach Inhalation proportional zur inhalierten CO-Menge und zur Hämoglobinmasse an. Dieser Anstieg wird über die CO-Hämoxymetrie ermittelt und resultierend aus der CO-Verdünnung die Hämoglobinmenge berechnet. Über die Hämoglobinkonzentration und den Hämatokrit kann im Anschluss das Blutvolumen berechnet werden. Grundsätzlich ist dieses Verfahren seit über 100 Jahren bekannt und wird seit ca. 1995 als Routinemethode zur Blutvolumenbestimmung in der Sportmedizin verwendet. Es existieren darüber hinaus methodische Probleme durch die CO-Abatmung und die Evaluierung in großen Kollektiven. Die hier vorgestellte Methodik beinhaltet die Weiterentwicklung der CO-Methode zur Direktmessung im geschlossenen System. Die Probanden atmen dabei ein exakt definiertes Bolus-Volumen in einem geschlossenen Atmungssystem über 15 Minuten ein. Die maximale Arbeitsplatzkonzentration (MAK: COHb 5%), also die resultierende COHb-Konzentration im Blut bei einer CO-Langzeitexposition von 35 ppm, wird in der Regel nur leicht überschritten. Dazu wurden an 104 Probanden zwei Vergleichsmessungen in definiertem Abstand und an 20 Probanden Wiederholungsmessungen nach Blutspende zum Nachweis der Reliabilität und Validität durchgeführt. Zusätzlich ist die Abfallkinetik von COHb an 20 Probanden bestimmt worden. Im Ergebnis stellt sich methodenbedingt ein COHb-Steady-State nach 9 Minuten Rückatmung im geschlossenen System ein. Der Typical-Error der Messwiederholung der Methodik liegt bei 1,9% bzw. nach weiterer Modifizierung der Methodik bei 1,3%. Der Nachweis eines Blutverlustes von 490 ml im Rahmen einer Blutspende zeigt nur eine minimale Abweichung von 10 g Hämoglobinmasse zwischen gemessenem und kalkuliertem Verlust. Die Halbwertszeit von COHb wurde mit 135 min bestimmt. Die verwendete Methodik zeigt aufgrund der induzierten COHb-Steady-State-Kinetik Vorteile bei der Anwendung und Genauigkeit. Der Nachweis der Wiederholbarkeit und Messgenauigkeit konnte an einem hinreichend großen Kollektiv gezeigt werden. Bei Mehrfachanwendung bietet die Sensitivität der Methodik die Möglichkeit der Aufdeckung von Manipulationen des Blutes über Erythropoetin (EPO) oder Eigenbluttransfusion. Dabei bewegt sich die eingesetzte CO-Belastung während der Methode im Bereich des Konsums von wenigen Zigaretten.

Newly created software is presented in magister degree thesis. The software was created for the innovative non–invasive cerebral blood flow autoregulation monitor which has no analogy in the global high tech market. It will be possible at first time to get diagnostic information about the cerebral blood flow autoregulation status of patient with severe brain injuries using such non–invasive monitoring technology in clinical practice. That will help with the individual treatment decision making. Clinical studies were conducted in neurosurgical intensive care units using created software. It has been shown that non–invasive and invasive cerebrovascular blood flow autoregulation monitoring technologies provide the same diagnostic information about the patient status. That conclusion is statistically significant and evidence based. Some R & D projects were performed using non–invasive cerebrovascular blood flow autoregulation monitor with implemented new software. The results of such projects were used in order to formulate the metrological – technological requirements for the final design and development of the innovative non–invasive blood flow autoregulation monitor. Such device is under creation in Telematics Scientific Laboratory which works together with Vittamed Technologijos Ltd and conducts 6.015 million Lt project (BPD04-ERPF-3.1.7-03-05/0020).

In this thesis, we included results from two studies. The first one considered the effects of the blood volume changes, during blood donation, on the heart rate variability (HRV) measured, non-invasively, form electrocardiographic (ECG) and photoplethysmographic (PPG) signals. Our results showed that, during blood donation, there were no significant changes in the pulsatile area of PPG signal, while heart rate increased. No significant changes were noticed in HRV extracted from both signals. Error analysis between the HRV extracted from ECG and peak interval variability (PIV) suggested that the error during blood donation was increased which means that the use of PIV extracted from PPG signal, used as a replacement diagnostic tool in clinical applications, needs further investigations and should be carefully studied in non-stationary cardiovascular situations such as blood donation. The imbalance between the two branches of the autonomic nervous system, sympathetic and parasympathetic, vagal, may result in a harmful activation of myocardial tissues which cause arrhythmias and sudden cardiac death. Although the study of the sympathovagal balance have been attracting many researchers, further studies are needed to elucidate the effects of many kinds of drugs on the autonomic modulation of the cardiac muscle, specifically, the cells of sinoatrial (SA) node. The aim of the second part of this thesis was to assess the effects of calcium channel blocker (Verapamil), calcium channel sensitizer (Levosimendan), calcium chloride (CaCl2), the combinations of verapamil/ CaCl2, levosimendan/ CaCl2, and noradrenaline infusion on beat-to-beat cardiovascular variability represented, in this research, by systolic blood pressure variability (SBPV), and stroke volume variability (SVV) signals. We used Fat Fourier Transform (FFT) to evaluate the power spectral density of the fluctuations in both signals to evaluate the effects of short-term treatments with those drugs on the sympathovagal balance in normal rats. Then, we compared the spectra obtained from SBPV and SVV to decide which of these fluctuations along with corresponding spectrum was more able to provide a clear feedback about the autonomic nervous system. Our data suggests that there were a significant correlations between low- (LF), mid- (MF), and high-frequency (HF) spectra obtained from SBPV and SVV except between the HF spectra estimated from after the infusion of levosimendan where a poor correlation (r = 0.530, p = 0.281) was noticed. This that both HF components obtained provide different information regarding the autonomic nervous system modulation of the SA node cells, while the results obtained from the rest of experiments showed that both signals provide same information about the modulation of sympathetic and parasympathetic tone due to all stages of different drugs infusion studied in this thesis. Besides that, we found that both spectra may be used to track the fluctuations in the cardiac output as a result of the drugs infusion.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 6 uppsatser.

Trata-se de estudo descritivo quantitativo, cujo objetivo foi analisar a aplicabilidade de intervenções da NIC, para situações de Volume de líquidos deficiente no Atendimento Préhospitalar Móvel Avançado à vítima de trauma. Os sujeitos do estudo foram 11 enfermeiros que atuam em Unidades Avançadas Pré-hospitalares da região de Ribeirão Preto. O estudo foi realizado em três etapas, na primeira, foram descritas pelos enfermeiros quais atividades eram realizadas para vítimas de trauma com diagnósticos de Volume de líquidos deficiente e Risco de volume de líquidos deficiente e aplicado um instrumento para apontar a aplicabilidade das intervenções e atividades contidas na NIC para os dois diagnósticos. Na segunda etapa, foram realizados o mapeamento cruzado das atividades e das intervenções da NIC para cada diagnóstico. Na terceira etapa, foram realizados o refinamento do mapeamento comparativo por enfermeiros expertos e a análise da opinião dos enfermeiros quanto à aplicabilidade das atividades à vítima de trauma. A seguir, foi realizada a proposta de reestruturação da NIC para situação de Volume de líquidos deficiente, no APH Avançado Móvel. Nos resultados identificamos 10 enfermeiros do sexo feminino, um do sexo masculino; um com doutorado, cinco com mestrado, quatro especialistas e um somente com graduação; quatro enfermeiros possuem entre 20 e 30 anos, dois entre 31 a 40 anos e cinco entre 41 e 50 anos; com relação ao tempo de atividade no APH Avançado Móvel, identificamos três enfermeiros com três anos, quatro entre quatro e cinco anos e quatro com seis anos ou mais nesse campo de assistência. Na primeira etapa identificaram-se 55 atividades descritas pelos enfermeiros para Volume de líquidos deficiente e 54 para Risco de volume de líquidos deficiente. No mapeamento cruzado, foram listadas 12 intervenções e 59 atividades das 30 intervenções e 750 atividades contidas na NIC, para o diagnóstico Volume de líquidos deficiente e, para Risco de volume de líquidos, 8 intervenções e 34 atividades das 28 intervenções e 691 atividades da NIC. Após refinamento do mapeamento cruzado pelos expertos, foi sugerido agregar as intervenções Encaminhamento, Gerenciamento de protocolo de emergência e Cuidados de emergência para ambos os diagnósticos e Controle de suprimentos para o diagnóstico Volume de líquidos deficiente. Foram refinadas, para Volume de líquidos deficiente, as seguintes intervenções: Controle da hipovolemia, Controle do choque: hipovolêmico, Monitoração hídrica, Terapia endovenosa, Controle do choque, Monitoração dos sinais vitais, Precauções contrassangramento, Punção venosa, Prevenção do choque, Redução do sangramento, Monitoração neurológica, Supervisão, Cuidados de emergência, Gerenciamento do protocolo de emergência, Controle de suprimentos e Encaminhamento e, para Risco de volume de líquidos deficiente, Controle da hipovolemia, Monitoração hídrica, Controle hídrico, Precauções contrassangramento, Prevenção do choque, Redução do sangramento, Supervisão, Sondagem gastrintestinal, Cuidados de emergência, Gerenciamento do protocolo de emergência e Encaminhamento. Na análise da aplicabilidade, foi considerado que as intervenções prioritárias, para Volume de líquidos deficiente, são Punção venosa (0,88) e Terapia endovenosa (0,81) e, para Risco de volume de líquidos, a intervenção Prevenção do choque (0,84). Na proposta de reorganização dos níveis de intervenções da NIC, sugerimos como prioritárias, para Volume de líquidos deficiente, Controle do choque, Monitoração de sinais vitais, Controle da hipovolemia e Supervisão e, para Risco de volume de líquidos deficiente, as intervenções Prevenção do choque e Supervisão. Concluímos que as intervenções contidas na NIC possuem aplicabilidade no cotidiano do APH Avançado Móvel e que algumas alterações devem ser realizadas para melhor utilização neste contexto. / It is a quantitative descriptive study, which aim was to examine the applicability of NIC interventions in situations of inadequate volume of fluid in the pre-hospital Advanced Mobile on the victim of trauma. The group responsible for this study was composed by 11 nurses who work in Advanced Pre-hospital units in the region of Ribeirão Preto. The study was conducted in three stages. The first one was a description given by the nurses, explaining which activities were performed on victims of trauma with diagnoses of fluid volume deficit and risk of fluid volume deficit and then was applied an instrument to indicate the applicability of interventions and activities contained the NIC for both diagnoses. In the second step, was performed a cross-mapping of the interventions and activities of the NIC for each diagnosis. In the third step, were performed by expert nurses the refinement of the cross-mapping and the analysis of the applicability of the activities to victims of trauma. Next, the proposal was to restructure the NIC to the fluid volume deficit victims in APH Advanced Mobile. Results identified that 10 nurses were female, one male. One with a doctorate, five with master, four specialists and only one with graduation. Four nurses have between 20 and 30 years, two between 31 to 40 years and five between 41 and 50 years. About the time of activity in APH Advanced Mobile, we identified three nurses with 3 years, four between 4 and 5 years and four with 6 or more years in this field for assistance. The first stage identified, through the nurses description, 55 activities for the fluid volume deficit treatment and 54 risk fluid volume deficit treatments. In the mapping cross were listed 12 interventions and 59 activities from 30 interventions and 750 activities contained in the NCI for this diagnosis. The results obtained for Risk of fluid volume deficit were 8 interventions and 34 activities of the 28 interventions and 691 activities contained in the NIC. After the refinement of the mapping cross by experts, it was suggested adding interventions Routing, Emergency management protocol and Emergency care for both diagnosis and Control of supplies for the diagnosis of fluid volume deficit. Were refined for fluid volume deficit the following interventions: Hypovolemia management, Shock management: volume , Fluid monitoring, intravenous therapy, Shock management, Vital signs monitoring, Bleeding precautions, Intravenous (IV) insertion, Shock prevention, Bleeding reduction, Neurological monitoring, Surveillance, Emergency care, Emergency Management, Protocol and Routing Control Supplies, and Risk of fluid volume deficit, Hypovolemia management, Fluid Monitoring, Bleeding precautions, Shock prevention, Bleeding reduction, Supervision, Gastrointestinal tube care, Emergency Care, Emergency Management and Routing Protocol. Analyzing the applicability, it was considered that the priority interventions for the fluid volume deficit are Intravenous (IV) insertion (0.88) and Intravenous therapy (0.81), and risk of fluid volume deficit, the impact Shock prevention (0,84). In the proposed reorganization of the levels of the NIC interventions, was suggested as a priority intervention for volume of fluid volume deficit, control of shock, vital signs Monitoring, supervision, hypovolermia management, and Risk of inadequate volume of fluid, the impact of prevention interventions and Supervision. We conclude that the interventions in the NIC have applicability in the daily lives of APH Advanced Mobile and that some changes should be made to a better use in this context.

Introdução: A Variação da Pressão Sistólica (VPS) e da Pressão de Pulso (VPP) têm sido propostas como métodos efetivos para monitoração hemodinâmica, em predizer a resposta à reposição da volemia durante a ventilação mecânica. A primeira é calculada pela diferença entre a pressão sistólica máxima e mínima em um ciclo respiratório, e composta pela somatória dos componentes delta up e delta down; e a VPP obtida pela diferença entre a pressão sistólica e diastólica também em um ciclo respiratório. O objetivo deste estudo foi avaliar a VPS e seus componentes, e a VPP durante a ventilação com volume (VCV) e pressão (PCV) controlados, em coelhos normovolêmicos ou submetidos à hemorragia controlada. Método: Trinta e dois coelhos foram distribuídos de forma aleatória em quatro grupos: G1-ConPCV, G2-HemPCV, G3-ConVCV e G4-HemVCV. Foram ventilados em PCV ou VCV, com volume corrente entre 10 e 12 ml.kg-1 e freqüência respiratória para manter normocapnia. Nos grupos controle (G1-ConPCV e G3-ConVCV), sangue não foi retirado, e cada momento foi avaliado por 30 minutos (M0, M1 e M2); nos grupos com hemorragia (G2-HemPCV e G4-HemVCV), não houve perda sangüínea em M0, em M1 retirou-se 15% da volemia estimada, assim como em M2, de forma gradual. Os dados foram submetidos à análise de variância para medidas repetidas (ANOVA), sendo considerados significativos para um valor de p<0,05, e apresentados na forma de média e desvio-padrão. Resultados: Não houve diferença em M0 entre os grupos estudados. Em M1, os grupos com perda sanguínea apresentaram maiores variações na VPS, em seu componente delta down e na VPP, diferindo significativamente apenas dos grupos controle. Quando a volemia foi reduzida em 30% (M2), G4-HemVCV apresentou maior variação na pressão sistólica, no componente delta down e na pressão de pulso; bem como ambos grupos submetidos à hemorragia apresentaram valores significativamente maiores do que os grupos controle. O débito cardíaco não apresentou variação significativa (p>0,05) entre os momentos e grupos estudados. Conclusões: Em coelhos normovolêmicos ou com hipovolemia leve, ambos modos de ventilação se comportam de forma semelhante sobre as variáveis estudadas, ao passo que na hipovolemia moderada pôde-se observar menor comprometimento hemodinâmico durante a PCV / Rationale: Systolic pressure variation (SPV) and pulse pressure variation (PPV) indices have been proposed as effective methods of hemodynamic monitoring to predict fluid responsiveness during mechanical ventilation. SPV is calculated by the difference between the maximum and minimum values of systolic blood pressure following a single positive pressure breath, and it is made up of the sum of their components delta up and delta down; PPV is obtained by the difference between systolic and diastolic blood pressure also in a single positive pressure breath. The purpose of this study was to evaluate SPV and its components, and PPV during volume (VCV) and pressure (PCV) controlled ventilation in normovolemic rabbits or ones submitted to graded hemorrhage. Method: Thirty two rabbits were randomly allocated in four groups: G1- ConPCV, G2-HemPCV, G3-ConVCV and G4-HemVCV. They were ventilated in PCV or VCV; tidal volume was fixed between 10 to 12 mL.kg-1 and respiratory rate was monitored in order to maintain normocapnia. In control groups (G1- ConPCV and G3-ConVCV) blood was not withdrawn and each moment was evaluated for 30 minutes (M0, M1 and M2); in hemorrhage groups (G2-HemPCV and G4-HemVCV) there was no blood loss in M0; in M1 and M2 15% of estimated volemia was graded withdrawn. Data were submitted to analysis of variance for repeated measures (ANOVA); significance level was p<0,05 and results were expressed as mean ± standard deviation. Results: In M0, no significant differences were observed among all groups. Hemorrhagic groups (G2-HemPCV and G4-HemVCV) presented higher SPV, delta down and PPV in M1, differing significantly (p<0,05) only from control groups. When 30% of estimated blood volume was removed, higher SPV, delta down and PPV were observed mainly in G4-HemVCV. Cardiac output did not vary significantly (p>0,05) among groups and moments. Conclusions: In rabbits with normovolemia or slight hemorrhage, both modes of ventilation had similar behavior over studied parameters, while in the ones undergoing moderate hemorrhage PCV determined less hemodynamic compromising

Magnetic resonance imaging (MRI) has emerged as the imaging modality of choice in a wide variety experimental and clinical applications. In this dissertation, I will describe novel MRI techniques for the characterization of neural and pulmonary vascular function in preclinical models of disease. In the first part of this dissertation, experimental results will be presented comparing the identification of ischemic lesions in experimental stroke using dynamic susceptibility contrast (DSC) and a well validated arterial spin labeling (ASL). We show that DSC measurements of an index of cerebral blood flow are sensitive to ischemia, treatment, and stroke subregions. Further, we derived a threshold of cerebral blood flow for ischemia as measured by DSC. Finally, we show that ischemic lesion volumes as defined by DSC are comparable to those defined by ASL. In the second part of this dissertation, a methodology of visualizing clots in experimental animal models of stroke is presented. Clots were rendered visible by MRI through the addition of a gadolinium based contrast agent during formation. Modified clots were used to induce an experimental embolic middle cerebral artery occlusion. Clots in the cerebral vasculature were visualized in vivousing MRI. Further, the efficacy of recombinant tissue plasminogen activator (r-tPA) and the combination of r-tPA and recombinant annexin-2 (rA2) was characterized by clot visualization during lysis. In the third part of this dissertation, we present results of the application of hyperpolarized helium (HP-He) in the characterization of new model of experimental pulmonary ischemia. The longitudinal relaxation time of HP-He is sensitive to the presence of paramagnetic oxygen. During ischemia, oxygen exchange from the airspaces of the lungs to the capillaries is hindered resulting in increased alveolar oxygen content which resulted in the shortening of the HP-He longitudinal relaxation time. Results of measurements of the HP-He relaxation time in both normal and ischemic animals are presented. In the final part of this dissertation, I will present results of a new method to measure pulmonary blood volume (PBV) using proton based MRI. A T1 weighted, inversion recovery spin echo sequence with cardiac and respiratory gating was developed to measure the changes in signal intensity of lung parenchyma before and after the injection of a long acting intravascular contrast agent. PBV is related to the signal change in the lung parenchyma and blood before and after contrast agent. We validate our method using a model of hypoxic pulmonary vasoconstriction in rats.

A administração intravenosa de solução salina hipertônica (HSS) induz alterações sistêmicas circulatórias como o aumento da pressão arterial e do volume circulante efetivo, além de ter efeitos locais sobre a microcirculação. No presente estudo foram analisados os efeitos produzidos pela administração de solução salina hipertônica 7,5% sobre a hemodinâmica do tumor através de estudos de imagem funcional e posteriormente, foi avaliado o seu potencial de otimizar a entrega de moléculas no tumor. A velocidade do sangue nos vasos tumorais estimada por Ultrassom Color Doppler foi aumentada após a injeção da HSS em comparação ao controle PBS em tumores de melanoma (B16F10 (p=0,019), SK-MEL-147 (p =0,028)) e de mama (4T1 (p=0,015)). Este mesmo efeito não foi observado nas artérias segmentarias do rim (p=0,476). Ultrassonografia com contraste por microbolhas (CEUS) foi realizada em xenoenxertos de tumor de melanoma (B16F10), carcinoma de cólon (HCT-116) e mama (MDA-MB-231), e como controle foi realizada imagem no rim e no músculo nos animais portadores destes tipos tumorais (n=3 por grupo). Após a injeção da HSS, o volume relativo de sangue foi aumentado nos tumores B16F10 (p=0,022) e HCT-116 (P = 0,039), mas o mesmo não foi observado com o tumor MDA-MB-231 (p=0,186). Além disso, não houve alterações nos tecidos normais (rim p = 0,957; músculo p = 0,104). Todos os testes estatísticos foram bicaudais. Quando a HSS foi utilizada como veículo para entrega de moléculas de baixo peso molecular como cisplatina e doxorrubicina no tratamento de tumores B16F10 e 4T1 respectivamente, não houve aumento da eficácia terapêutica, avaliada através do crescimento tumoral e peso dos tumores. O efeito da HSS sobre a retenção de macromoléculas nos tumores SK-Mel- 147 e 4T1, avaliado através de imagem por epifluorescência do contraste ótico IR-783, não foi suficientemente notório para rejeitar a hipótese nula. Assim, a HSS induz um aumento transitório na velocidade do sangue e do volume sanguíneo, de maneira relativamente seletiva para os tumores avaliados, com exceção do MDA-MB-231. Portanto, esta pode ser uma estratégia útil para aumentar a entrega de moléculas e otimizar tanto o efeito terapêutico, quanto o diagnóstico por imagem / Intravenous administration of Hypertonic saline solution (HSS) induces systemic circulatory changes including blood pressure rising, effective circulating volume increase as well as local effects on microvasculature. We analyzed the effects produced by Hypertonic Saline 7,5% administration on tumor hemodynamics through functional imaging studies as well as whether it enhances molecular delivery in tumor tissue when used as a vehicle. Blood velocity assessed by Color Doppler Ultrasound was increased after HSS injection compared to PBS in the following tumors: B16F10 (p=0,019), SKMEL- 147 (p=0,028) and 4T1 (p=0,015). No statistical difference was observed on the segmental kidney arteries (p=0,476). Dynamic Contrast enhanced ultrasound (CEUS) was done in B16F10, HCT-116 and MDA-MB-231 tumor xenografts, kidney and muscle tissues (n=3 per group). After HSS injection, relative blood volume was increased in B16F10 (p=0,022) and HCT-116 (p=0,039) but not on MDA-MB-231 (p=0,186). Changes on normal tissues were not statistically different (kidney p=0,957; muscle p=0,104). All statistical tests were two-sided. Administration of HSS as a vehicle for low molecular weight molecules cisplatin and doxorubicin in the treatment of B16F10 and 4T1 tumors respectively had no significant improvement of therapeutic efficacy, estimated by tumor growth and tumor weight measurements. Effect of HSS over retention of macromolecules in tumors SK-Mel-147 and 4T1, evaluated by epifluorescence imaging of the optical contrast IR- 783 was not large enough to reject the null hypothesis. HSS induces a transient increase in velocity of the blood as well as the blood volume that is relatively selective for the evaluated tumors with exception of MDA-MB-231. Data suggest that HSS administration might be a useful strategy to increase the delivery of molecules and optimize both therapy and diagnostic imaging

A administração intravenosa de solução salina hipertônica (HSS) induz alterações sistêmicas circulatórias como o aumento da pressão arterial e do volume circulante efetivo, além de ter efeitos locais sobre a microcirculação. No presente estudo foram analisados os efeitos produzidos pela administração de solução salina hipertônica 7,5% sobre a hemodinâmica do tumor através de estudos de imagem funcional e posteriormente, foi avaliado o seu potencial de otimizar a entrega de moléculas no tumor. A velocidade do sangue nos vasos tumorais estimada por Ultrassom Color Doppler foi aumentada após a injeção da HSS em comparação ao controle PBS em tumores de melanoma (B16F10 (p=0,019), SK-MEL-147 (p =0,028)) e de mama (4T1 (p=0,015)). Este mesmo efeito não foi observado nas artérias segmentarias do rim (p=0,476). Ultrassonografia com contraste por microbolhas (CEUS) foi realizada em xenoenxertos de tumor de melanoma (B16F10), carcinoma de cólon (HCT-116) e mama (MDA-MB-231), e como controle foi realizada imagem no rim e no músculo nos animais portadores destes tipos tumorais (n=3 por grupo). Após a injeção da HSS, o volume relativo de sangue foi aumentado nos tumores B16F10 (p=0,022) e HCT-116 (P = 0,039), mas o mesmo não foi observado com o tumor MDA-MB-231 (p=0,186). Além disso, não houve alterações nos tecidos normais (rim p = 0,957; músculo p = 0,104). Todos os testes estatísticos foram bicaudais. Quando a HSS foi utilizada como veículo para entrega de moléculas de baixo peso molecular como cisplatina e doxorrubicina no tratamento de tumores B16F10 e 4T1 respectivamente, não houve aumento da eficácia terapêutica, avaliada através do crescimento tumoral e peso dos tumores. O efeito da HSS sobre a retenção de macromoléculas nos tumores SK-Mel- 147 e 4T1, avaliado através de imagem por epifluorescência do contraste ótico IR-783, não foi suficientemente notório para rejeitar a hipótese nula. Assim, a HSS induz um aumento transitório na velocidade do sangue e do volume sanguíneo, de maneira relativamente seletiva para os tumores avaliados, com exceção do MDA-MB-231. Portanto, esta pode ser uma estratégia útil para aumentar a entrega de moléculas e otimizar tanto o efeito terapêutico, quanto o diagnóstico por imagem / Intravenous administration of Hypertonic saline solution (HSS) induces systemic circulatory changes including blood pressure rising, effective circulating volume increase as well as local effects on microvasculature. We analyzed the effects produced by Hypertonic Saline 7,5% administration on tumor hemodynamics through functional imaging studies as well as whether it enhances molecular delivery in tumor tissue when used as a vehicle. Blood velocity assessed by Color Doppler Ultrasound was increased after HSS injection compared to PBS in the following tumors: B16F10 (p=0,019), SKMEL- 147 (p=0,028) and 4T1 (p=0,015). No statistical difference was observed on the segmental kidney arteries (p=0,476). Dynamic Contrast enhanced ultrasound (CEUS) was done in B16F10, HCT-116 and MDA-MB-231 tumor xenografts, kidney and muscle tissues (n=3 per group). After HSS injection, relative blood volume was increased in B16F10 (p=0,022) and HCT-116 (p=0,039) but not on MDA-MB-231 (p=0,186). Changes on normal tissues were not statistically different (kidney p=0,957; muscle p=0,104). All statistical tests were two-sided. Administration of HSS as a vehicle for low molecular weight molecules cisplatin and doxorubicin in the treatment of B16F10 and 4T1 tumors respectively had no significant improvement of therapeutic efficacy, estimated by tumor growth and tumor weight measurements. Effect of HSS over retention of macromolecules in tumors SK-Mel-147 and 4T1, evaluated by epifluorescence imaging of the optical contrast IR- 783 was not large enough to reject the null hypothesis. HSS induces a transient increase in velocity of the blood as well as the blood volume that is relatively selective for the evaluated tumors with exception of MDA-MB-231. Data suggest that HSS administration might be a useful strategy to increase the delivery of molecules and optimize both therapy and diagnostic imaging