臂叢阻滯麻醉可以阻斷同側正中神經，尺神經，橈神經和肌皮神經，故其經常被用於上肢手術中麻醉和/或鎮痛。臂叢阻滯麻醉也可以阻滯同側交感神經，導致同側上肢血管擴張（動脈和靜脈）和血流增加。脈沖多普勒超聲技術可以檢測到這些局部的血流動力學變化。文獻回顧表明迄今為止發表的大部分報道片面地評估了臂叢阻滯麻醉後上肢的局部血流動力學變化缺乏全面而系統的研究，並且報道中關於脈沖多普勒超聲技術用於上肢局部血流動力學測量的可靠性和可重復性的數據也很有限。此外，上肢的局部血流動力學變化是否與測量的位置或者使用的臂叢阻滯麻醉技術有關尚且未知。 / 我假設脈沖多普勒超聲是壹種可靠的測量上肢血流動力學變化的方法，它可以系統地定量測定臂叢阻滯麻醉後上肢的局部血流動力學變化，確定這些變化在上肢不同部位的差異，以及確定不同臂叢阻滯麻醉技術後局部血流動力學變化的差異。以下的部分列舉了本博士課題中開展的壹系列研究來證實我的假設。 / 第壹，我們在12個健康年輕誌願者中（年齡21-34歲）用脈沖多普勒超聲在上肢肱動脈和指掌側總動脈進行血流動力學測量，評估其在觀察者內和觀察者間的差異性。兩個觀察者獨立進行了測量。測量的指標包括收縮期峰值血流速度（厘米/秒），舒張末期血流速度（厘米/秒），收縮期峰值血流速度和舒張末期血流速度比值，平均速度（厘米/秒），時均速度（厘米/秒），阻力指數，搏動指數，動脈直徑（厘米），和血流量（毫升/分鐘）。結果顯示脈沖多普勒超聲是壹種可靠的方法，可用來重復測量上肢的局部血流動力學參數（組內相關系數>0.9）. / 第二，我們在8個病人中（年齡24-70歲）系統地評估了超聲波引導下的腋路臂叢神經阻滯後同側肱動脈的局部血流動力學變化。結果表明臂叢神經阻滯後最早的變化是脈沖多普勒頻譜波形的變化，其波形由三相變為單相，舒張期血流曲線擡升。隨著時間推移，收縮期峰值血流速度，舒張末期血流速度，平均速度，時均速度，動脈直徑，和血流量均顯著增加，收縮期峰值血流速度和舒張末期血流速度比值，阻力指數，搏動指數顯著降低。大部分變化發生在神經阻滯後5分鐘。在所有的局部血流動力學指標中，舒張末期血流速度表現出最顯著的變化（3.7倍），其增加超過收縮期峰值血流速度（1.5倍）和平均速度（2.8倍）。 / 第三，利用15個病人（年齡23-70歲），我們評估了超聲波引導下的鎖骨上臂叢神經阻滯後上肢近端動脈（肱動脈）和遠端動脈（指掌側總動脈）血流動力學變化的差異。臂叢神經阻滯之後，在能量多普勒圖像上，指掌側總動脈表現出更明顯的血管擴張。在脈沖多普勒頻譜波形中，兩個動脈均出現舒張早期的反流消失以及舒張期曲線擡升。另外，收縮期峰值血流速度，舒張末期血流速度，平均速度，時均速度，動脈直徑，和血流量增加，收縮期峰值血流速度和舒張末期血流速度比值，阻力指數，搏動指數顯著降低。這些指標的相對變化在指掌側總動脈比肱動脈更顯著。此研究中，4個病人出現對側手部溫度的增加，以此推測局部麻醉藥的雙側擴散。 / 第四，我們開展了壹項前瞻性隨機對照研究來比較腋路和鎖骨上臂叢神經阻滯引起的局部血流動力學變化的不同。兩組病人人口統計學資料類似。兩種臂叢神經阻滯技術均引起肱動脈和指掌側總動脈收縮期峰值血流速度，舒張末期血流速度，平均速度，時均速度，動脈直徑，和血流量的顯著增加，收縮期峰值血流速度和舒張末期血流速度比值，阻力指數，搏動指數顯著降低。跟腋窩方法相比，鎖骨上技術能夠引起肱動脈時均速度和血流量更顯著的增加。然而，在感覺神經阻滯起效方面，腋窩方法比鎖骨上方法更快。 / 總之，脈沖多普勒超聲可重復地測量肱動脈和指掌側總動脈的血流動力學參數及其變化。臂叢阻滯麻醉引起肱動脈和指掌側總動脈脈沖多普勒頻譜形態的變化，血流速度的增加和血流量的增加。這些局部血流動力學變化在指掌側總動脈中比肱動脈更顯著。鎖骨上臂叢神經阻滯比腋窩方法引起更顯著的局部血流動力學變化。臨床醫生可以利用上肢遠端動脈的局部血流動力學變化來評價臂叢阻滯麻醉的交感神經阻滯效應。麻醉醫師還可以根據這些發現為術後需要較好血流灌註的上肢血管手術選取臂叢神經阻滯方法。 / Brachial plexus block (BPB), which produces sensory and motor blockade of the ipsilateral median, ulnar, radial and musculocutaneous nerves, is frequently used for anesthesia and/or analgesia during surgical procedures of the upper extremity. BPB also produces ipsilateral sympathetic nerve blockade that is characterized by vasodilatation (venous and arterial), and an increase in blood flow to the ipsilateral upper extremity. Pulsed wave Doppler (PWD) ultrasound (US) has been used to evaluate these regional hemodynamic changes. A review of the literature shows that most published reports to date have only partially evaluated the regional hemodynamic changes in the upper extremity after a BPB. There are also limited data demonstrating that PWD US is a reliable or reproducible method of quantifying the regional hemodynamic changes in the upper extremity. Moreover, it is also not known whether the regional hemodynamic changes vary with the site of measurement or the technique of BPB used. / I hypothesized that PWD US is a reliable method for measuring regional hemodynamic parameters in the upper extremity. It can be used to comprehensively quantify the regional hemodynamic changes after a BPB and to determine the extent of these changes at different sites in the upper extremity and after different techniques for BPB. The following section outlines a series of studies that I undertook during this PhD project to corroborate my hypothesis. / Firstly, we sought to assess the intra-observer and inter-observer variability of measuring regional hemodynamic parameters, in the brachial and common palmar digital arteries of the upper extremity, using PWD US in 12 healthy young volunteers aged 21-34 yrs. The measurements were performed independently by two observers. Measured hemodynamic parameters included peak systolic velocity (PSV, cm/s), end diastolic velocity (EDV, cm/s), ratio of PSV and EDV (S/D), mean velocity (Vmean, cm/s), time-averaged mean velocity (TAVM, cm/s), resistance index (RI), pulsatility index (PI), the arterial diameter (d, cm), and blood flow (mL/min). The results showed that PWD US is a reliable and reproducible method of measuring regional hemodynamic parameters in the upper extremity (ICC>0.9). / Secondly, we comprehensively evaluated the regional hemodynamic changes in the ipsilateral brachial artery after an ultrasound guided (USG) axillary BPB in eight adult patients aged 24-70 yrs. Our results suggested that the earliest change after the BPB was a change in the morphology of the PWD spectral waveform from a triphasic to a monophasic waveform and an elevation in the diastolic blood flow velocity. Over time, there was also a significant increase in PSV, EDV, Vmean, TAVM, d, and blood flow, and a decrease in S/D ratio, RI, and PI. Most of these changes were seen as early as 5 minutes after the block. The increase in EDV (3.7-fold) was the most notable change, and it was significantly greater than the increase in PSV (1.5-fold) and Vmean (2.8-fold). / Thirdly, the regional hemodynamic changes in the proximal (brachial artery) and distal (common palmar digital artery) artery of the upper extremity after an USG supraclavicular BPB was investigated in 15 adult patients aged 23-70 yrs. After the block, the common palmar digital artery showed more obvious vasodilatation on the power Doppler US scan. In the PWD spectral waveform, and in both arteries studied, the protodiastolic blood flow disappeared and there was an elevation of the diastolic curve. Also there was a significant increase in PSV, EDV, Vmean, TAVM, d, and blood flow, and a significant reduction in S/D ratio, PI and RI in both arteries. Relative changes of these parameters were greater in the common palmar digital artery than in the brachial artery. In this study, bilateral spread of local anesthetic was observed in 4 patients, as evidenced by an increase of skin temperature on the contralateral hand. / Fourthly, a prospective and randomized study was conducted to compare the regional hemodynamic changes in the upper extremity after an axillary and supraclavicular BPB. The two study groups were similar with respect to demographic data. Both axillary and supraclavicular BPB caused a significant increase in PSV, EDV, Vmean, TAVM, d, and blood flow, and a significant reduction in S/D ratio, PI and RI in both the brachial and common palmar digital arteries. Compared with the axillary approach, the supraclavicular approach produced significantly greater increases in TAVM and blood flow in the brachial artery. However, the onset of sensory blockade was faster after the axillary BPB than with the supraclavicular BPB. / In conclusion, PWD US is a reliable and reproducible method for quantifying the regional hemodynamic parameters in both the brachial and common palmar digital arteries. BPB produces a change in the morphology of the PWD spectral waveform, arterial vasodilatation, an increase in blood flow velocity, and an increase in blood flow in both the ipsilateral brachial and common palmar digital arteries. These changes in regional hemodynamic parameters were more profound in the common palmar digital artery than in the brachial artery. Also these changes were more significant after a supraclavicular BPB than after an axillary BPB. These findings will allow clinicians to evaluate the sympathetic effect of a BPB using regional hemodynamic changes in the distal arteries of the upper extremity. These findings will also allow anesthesiologists to make an evidence-based choice on the techniques of BPB for vascular surgery of the upper extremity when good tissue perfusion is desirable postoperatively. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Li, Jiawei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 182-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / TABLE OF CONTENTS / ABSTRACT / 中文摘要 / STATEMENT OF WORK / ACKNOWLEDGMENTS / PUBLICATIONS AND PRESENTATIONS / LIST OF ABBREVIATIONS / LIST OF TABLES / LIST OF FIGURES / Chapter CHAPTER 1 --- Introduction / Chapter 1.1 --- Introduction / Chapter 1.2 --- Aims of the project / Chapter 1.3 --- Outline of the thesis / Chapter CHAPTER 2 --- Literature Review / Chapter 2.1 --- Introduction / Chapter 2.2 --- Why regional hemodynamic changes occur after a BPB / Chapter 2.2.1 --- Anatomy of the sympathetic nervous system in the upper extremity / Chapter 2.2.2 --- The anatomic relationship between the sympathetic nerves and the brachial plexus / Chapter 2.2.3 --- Sympathetic efferents to blood vessels in the upper extremity / Chapter 2.3 --- Methods used to measure regional hemodynamic changes / Chapter 2.3.1 --- Skin and muscle blood flow / Chapter 2.3.2 --- Regional hemodynamic measurements using PWD US / Chapter 2.3.2.1 --- Basics of Doppler ultrasound / Chapter 2.3.2.2 --- Principles of blood flow / Chapter 2.3.2.3 --- Spectral analysis of blood flow using PWD US / Chapter 2.4 --- Published data on regional hemodynamic changes after BPB / Chapter 2.4.1 --- Skin temperature / Chapter 2.4.2 --- Cutaneous and muscular blood flow / Chapter 2.4.3 --- Regional hemodynamic measurements on major arterial branches of the upper extremity / Chapter 2.5 --- Introduction of BPB / Chapter 2.5.1 --- Anatomy of the brachial plexus / Chapter 2.5.2 --- Techniques for performing BPB / Chapter 2.5.3 --- USG BPB / Chapter 2.5.3.1 --- History / Chapter 2.5.3.2 --- Advantages of ultrasound guidance for peripheral nerve blockade / Chapter CHAPTER 3 --- Methodology / Chapter 3.1 --- Introduction / Chapter 3.2 --- Patient preparations / Chapter 3.3 --- Regional hemodynamic measurement / Chapter 3.3.1 --- Ultrasound equipment / Chapter 3.3.2 --- Patient position / Chapter 3.3.3 --- Regional hemodynamic measurements using PWD US / Chapter 3.3.3.1 --- Optimizing settings for B-Mode US / Chapter 3.3.3.2 --- Optimizing settings for PWD US / Chapter 3.3.3.3 --- Measurement of regional hemodynamic parameters / Chapter 3.3.4 --- Measurement of diameter (d) and blood flow (Q) / Chapter 3.4 --- USG BPB / Chapter 3.4.1 --- USG axillary BPB / Chapter 3.4.1.1 --- Scout scan / Chapter 3.4.1.2 --- Aseptic precautions / Chapter 3.4.1.3 --- USG axillary BPB / Chapter 3.4.2 --- USG supraclavicular BPB / Chapter 3.4.2.1 --- Scout scan / Chapter 3.4.2.2 --- Aseptic precautions / Chapter 3.4.2.3 --- USG supraclavicular BPB / Chapter 3.5 --- Outcome data after the BPB / Chapter CHAPTER 4 --- Measurement of Regional Hemodynamic Parameters in the Upper Extremity Using Pulsed Wave Doppler Ultrasound: A Reliability Study / Chapter 4.1 --- Introduction / Chapter 4.2 --- Methods / Chapter 4.2.1 --- Subjects / Chapter 4.2.2 --- Study design / Chapter 4.2.3 --- Data acquisition / Chapter 4.2.4 --- Statistical analysis / Chapter 4.3 --- Results / Chapter 4.4 --- Discussion / Chapter 4.4.1 --- Summary of main findings / Chapter 4.4.2 --- Compared with previous studies / Chapter 4.4.3 --- Sources of measurement variability / Chapter 4.4.4 --- Explanation for the variation in the changes in various regional hemodynamic parameters / Chapter 4.5 --- Conclusion / Chapter CHAPTER 5 --- Regional Hemodynamic Changes after an Axillary BPB: A Pulsed Wave Doppler Ultrasound Study / Chapter 5.1 --- Introduction / Chapter 5.2 --- Methods / Chapter 5.2.1 --- Patient enrollment / Chapter 5.2.2 --- Patient preparation / Chapter 5.2.3 --- Measurement of baseline regional hemodynamic parameters / Chapter 5.2.4 --- USG axillary BPB / Chapter 5.2.5 --- Outcome data after the BPB / Chapter 5.2.6 --- Sensory and motor assessments after the BPB / Chapter 5.2.7 --- Statistical Analysis / Chapter 5.3 --- Results / Chapter 5.4 --- Discussion / Chapter 5.4.1 --- Summary of main findings / Chapter 5.4.2 --- Limitations / Chapter 5.4.3 --- Changes in PWD spectral waveform / Chapter 5.4.4 --- Changes in regional hemodynamic parameters / Chapter 5.4.5 --- Increase in skin temperature / Chapter 5.4.6 --- Effects of local anesthetic / Chapter 5.5 --- Conclusion / Chapter CHAPTER 6 --- Does a Supraclavicular Brachial Plexus Block Induce Comparable Hemodynamic Changes in the Proximal and Distal Arteries of the Upper Extremity? / Chapter 6.1 --- Introduction / Chapter 6.2 --- Methods / Chapter 6.2.1 --- Patient recruitment / Chapter 6.2.2 --- Patient preparation / Chapter 6.2.3 --- Measurement of baseline regional hemodynamic parameters, arterial diameter and blood flow / Chapter 6.2.4 --- USG supraclavicular BPB / Chapter 6.2.5 --- Outcome measurements after the BPB / Chapter 6.2.6 --- Statistical analysis / Chapter 6.3 --- Results / Chapter 6.4 --- Discussion / Chapter 6.4.1 --- Summary of the main findings / Chapter 6.4.2 --- Limitations / Chapter 6.4.3 --- Changes in the PWD spectral waveform / Chapter 6.4.4 --- Explanation of the differences in regional hemodynamic changes in the distal and proximal arteries after BPB / Chapter 6.4.5 --- Increase in skin temperature and its relation to blood flow / Chapter 6.4.6 --- Bilateral sympathetic effect after supraclavicular BPB / Chapter 6.4.7 --- Other findings of this study / Chapter 6.5 --- Conclusion / Chapter CHAPTER 7 --- Does a Supraclavicular Brachial Plexus Block Induce Greater Changes in Regional Hemodynamics than an Axillary Brachial Plexus Block? / Chapter 7.1 --- Introduction / Chapter 7.2 --- Methods / Chapter 7.2.1 --- Sample size estimation / Chapter 7.2.2 --- Exclusion criteria / Chapter 7.2.3 --- Randomized allocation / Chapter 7.2.4 --- Preparations before the ultrasound scan / Chapter 7.2.5 --- Measurement of baseline regional hemodynamic parameters, diameter and blood / Chapter 7.2.6 --- USG axillary and supraclavicular BPB / Chapter 7.2.7 --- Outcome measurements after the BPB / Chapter 7.2.8 --- Statistical analysis / Chapter 7.3 --- Results / Chapter 7.4 --- Discussion / Chapter 7.4.1 --- Summary of the main findings / Chapter 7.4.2 --- Limitations / Chapter 7.4.3 --- Change in the PWD spectral waveform / Chapter 7.4.4 --- Differences in regional hemodynamic changes between the 2 study groups / Chapter 7.4.5 --- Differences in sensory and motor blockade between the 2 study groups / Chapter 7.4.6 --- Changes in skin temperature / Chapter 7.5 --- Conclusion / Chapter CHAPTER 8 --- Summary and Conclusions / APPENDIX / REFERENCES

INTRODUÇÃO: Evidencia experimental sugere que padrões alterados de fluxo vascular, associados às bifurcações, estão envolvidos no desenvolvimento de lesões aneurismáticas. Pesquisamos os efeitos que a sobrecarga hemodinâmica condiciona sobre a parede arterial do ápice da bifurcação aórtica de modelos murinos. MÉTODOS: Sessenta ratos Wistar, selecionados e designados mediante amostragem probabilística simples foram agrupados equitativamente em um grupo controle e três grupos experimentais. Os espécimes foram anestesiados e sob magnificação microscópica, foi realizada uma incisão abdominal média e a aorta e os vasos ilíacos abordados e isolados desde a porção infra-renal até a porção distal da bifurcação. Modificação da geometria da bifurcação aórtica foi realizada mediante tunelamento da porção distal da artéria ilíaca no músculo ílio-lombar, no nível da raiz do membro inferior nos grupos II e IV. Nefrectomia esquerda e ligação da artéria renal inferior direita foram completadas para reforçar o estresse hemodinâmico nos grupos III e IV. Os modelos mantiveram-se em condições de laboratório convencionais com dieta standard para a espécie e água ad libitum para os grupos I e II e solução de NaCl 0,9% para os grupos III e IV. Após seis meses de seguimento, a bifurcação aórtica e as artérias ilíacas foram inspecionadas e subseqüentemente removidas para sua análise histopatológica. Um espécime por cada grupo foi submetido à angiografia digital com reconstrução tridimensional da bifurcação aórtica. RESULTADOS: 1) A pressão arterial, a freqüência cardíaca e a pressão de pulso entre os grupos, com e sem nefrectomia, mostraram diferenças com significância estatística (p <0,05). Os espécimes reunidos nos grupos III e IV que receberam sobrecarga de sódio desenvolveram um padrão hemodinâmico caracterizado por incremento da freqüência cardíaca e da pressão de pulso. 2) Seis espécimes (60%) do grupo IV desenvolveram aneurismas do ápice da bifurcação aórtica. 3) A avaliação angiográfica demonstrou que a morfologia da bifurcação do grupo controle se mantém sem modificações aparentes durante o período de seguimento. Entretanto, o grupo II apresenta dados de remodelamento longitudinal com tortuosidade e alongamento do tronco e ramos que conformam a bifurcação. Já o grupo III apresenta estenose proximal e dilatação incipiente da região do ápice da bifurcação em um padrão descrito como blister-like. Finalmente, o grupo IV demonstra aneurismas e estenoses múltiplas da porção proximal e distal ao divisor de fluxo. CONCLUSÕES: Em modelos murinos, deformações da geometria arterial, introduzidas por mudanças do ângulo de bifurcação, induzem a formação de aneurismas e a associação com hipertensão arterial, pressão de pulso aumentada, freqüência cardíaca elevada e sobrecarga de sódio potencializam a dilatação sacular desses segmentos / BACKGROUND: Experimental evidence indicates that altered patterns of vascular flow associated with bifurcations are involved in the development of aneurysmatic lesions. The effects of the hemodynamic overload on the arterial wall of the aortic bifurcation in murine models were studied. METHODS: Sixty Wistar rats were selected and assigned by simple random sampling into a control group and three experimental groups. The specimens were anesthetized. Under microscopic magnification an abdominal incision was performed and the aortic and iliac vessels were isolated from the infra-renal portion until the distal bifurcation. The modification of the geometry of the aortic bifurcation was accomplished by tunneling of the distal iliac artery into ilio-lumbar muscle in groups II and IV. Left nephrectomy and ligation of inferior right renal artery were completed to enhance the hemodynamic stress in groups III and IV. The models were maintained in conventional laboratory conditions with standard diet for the species and water ad libitum for groups I and II, and NaCl 0.9% for groups III and IV. After six months of follow up, the aortic bifurcation and iliac arteries were inspected and subsequently removed to its histopathological evaluation. One specimen from each group underwent angiography with digital three-dimensional reconstruction of the aortic bifurcation prior to sacrifice. RESULTS: 1) Blood pressure, heart rate and pulse pressure between the groups with and without nephrectomy showed statistically significant differences (p <0.05). The specimens collected in groups III and IV who received sodium overload developed a hemodynamic pattern characterized by increased heart rate and pulse pressure. 2) Six specimens (60%) in group IV developed aneurysmatic dilatation of the apex of the aortic bifurcation. 3) The angiographic evaluation showed that the morphology of the bifurcation of the control group remains unchanged during the study period. However, group II presents data from longitudinal remodeling with tortuosity and lengthening of the trunk and branches that make up the fork. The Group III presents stenosis and proximal dilatation of the apex of the bifurcation in a pattern described as blister-like. Finally, Group IV shows multiple stenosis proximal and distal to the flow divider. CONCLUSIONS: In murine models, the geometry deformation introduced by changes in the angle of bifurcation, induce inflammation of the flow divider, whereas, high blood pressure, pulse pressure, heart rate and high sodium overload catalyze the aneurysmatic dilatation of these segments

Orientador: Norma Sueli Pinheiro Módolo / Resumo: Diversos modelos experimentais têm sido utilizados para ilustrar as alterações hemodinâmicas e metabólicas que ocorrem durante o choque hemorrágico. O objetivo da pesquisa é observar os comportamentos hemodinâmicos e metabólicos que acontecem em um modelo seqüencial e progressivo de choque hemorrágico em cão, verificando quais índices alteram-se mais precocemente. Metodologia: O estudo foi realizado em 13 cães sob anestesia intravenosa total com pentobarbital sódico, em normoventilação e previamente esplenectomizado. Os animais não foram hidratados e a velocidade do sangramento foi ditada pela pressão arterial em que o animal se encontrava. Os atributos estudados foram divididos em hemodinâmicos (freqüência cardíaca - FC, pressão arterial média - PAM, índice de resistência vascular sistêmica - IRVS, índice sistólico - IS, índice cardíaco - IC, índice de choque - I. choque, índice de trabalho sistólico do ventrículo esquerdo - ITSVE, pressão capilar pulmonar - PCP, pressão venosa central - PVC) e metabólicos (saturação venosa mista - SvO2, pressão venosa de oxigênio - PvO2, transporte de oxigênio - DO2, consumo de oxigênio - VO2, Extração de oxigênio - TEO2, lactato sérico - Lactato). A coleta de dados e os atributos foram estudados em 6 momentos distintos: M1 - controle, M2 - sangramento de 10% da volemia calculada para o animal, M3 - sangramento de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Many experimental models have been used to elucidate hemodynamic and metabolic alterations that occur during the hemorrhagic shock. The aim of this research is to observe hemodynamic and metabolic behaviours present in a sequential and progressive model of hemorrhagic shock in dogs, verifying which indexes change more precociously. Methods: This study was performed in 13 dogs under total intravenous anesthesia with sodic pentobarbital, with standart ventilation and formerly splenectomized. The animals were not hydrated and the bleeding velocity was according to the blood pressure of the animal. The studied parameters were divided into hemodynamics (heart rate - HR, mean arterial blood pressure - MAP, sistemic vascular resistance index - SVRI, sistolic index - SI, cardiac index - CI, shock index - S index, sistolic function of the left ventricle index - SFLVI, pulmonary capillary pressure - PCP, central venous pressure - CVP) and metabolics (mixed venous saturation - MVS, venous oxigen pressure - VOP, oxygen transport - OT, oxygen consumption - OC, oxygen extraction - OE and seric lactate). The results and parameters were evaluated in 6 different moments: M1 - control, M2 - bleeding of 10% of calculated volemic for the animal, M3 - increase of 10% in bleeding, M4 - increase of 10% in bleeding, M5 - increase... (Complete abstract, click electronic access below) / Mestre

Introdução: Devido ao aumento do volume abdominal, a posição prona é difícil e desconfortável para a gestante. Por isso, até hoje não foi testado se, nessa posição, a grávida teria seus padrões hemodinâmicos materno-fetais alterados. Objetivos: Analisar a influência da posição prona nos parâmetros hemodinâmicos materno-fetais e no conforto da mulher grávida, em um protótipo de maca especialmente construído para gestantes. Método: Estudo prospectivo, observacional e transversal, com 30 gestantes, em seguimento pré-natal, e 16 não gestantes, como grupo de controle. Os dois grupos foram subdivididos para participar de dois tipos de sequências randomizadas de posições, investigando-se se a mudança na ordem das sequências traria, nas gestantes e seus fetos, alguma variação significativa de valores hemodinâmicos. As posições utilizadas neste estudo foram: prona, supina, semissentada e decúbito lateral esquerdo. Foram avaliados os seguintes parâmetros hemodinâmicos: frequência cardíaca, pressão arterial sistólica, pressão arterial diastólica, saturação de oxigênio e frequência respiratória maternos e linha de base e variabilidade fetais. Para a análise estatística, foi utilizada a análise não paramétrica para medidas repetidas; e, para verificar se a posição anterior à prona teria alguma influência no desempenho dessa última, foram criadas variáveis de variação, que foram comparadas pelo teste de Wilcoxon. Resultados: Comparandose os índices da posição prona aos obtidos nos demais posicionamentos, observou-se que todos os parâmetros mantiveram-se dentro dos valores de normalidade e não houve, nesses valores, interferência das posições anteriores à prona. O grupo de gestantes revelou médias significativamente maiores do que as do grupo de não gestantes em relação às frequências cardíaca (p < 0,004), na sequência 1; e p < 0,001, na 2) e respiratória (na sequência 1, p=0,041; e, na 2, p=0,012). Na análise do grupo de gestantes, observou-se que, em ambas as sequências, as pressões arteriais sistólica e diastólica apresentaram, na posição prona, valores menores que os apresentados nas demais posições. Nesse grupo, observou-se diferença significativa na pressão arterial sistólica, quando se comparou, na sequência 1, a posição prona à semissentada (p < 0,001), à supina (p < 0,01) e ao decúbito lateral esquerdo (p < 0,01); e, na sequência 2, quando se comparou a posição prona às semissentada (p < 0,001) e à supina (p=0,013). Ainda no grupo de grávidas, a pressão arterial diastólica apresentou diferença significativa nas duas sequências: na sequência 1, a posição prona foi comparada às posições semissentada (p < 0,006), supina (p=0,023) e decúbito lateral esquerdo (p=0,017); na sequência 2, foi comparada ao posicionamento semissentado (p < 0,005) e supino (p=0,008). Quanto à saturação do oxigênio, na sequência 2 do grupo de grávidas houve diferença significativa quando se compararam os valores obtidos na posição prona aos obtidos na semissentada (p=0,021) e na supina (p=0,003). Em ambas as sequências, não houve diferença significativa na linha de base fetal, quando se comparou a posição prona com o decúbito lateral esquerdo. Não foram observadas variações significativas na variabilidade fetal nas sequências avaliadas. Todas as pacientes declararam terem se sentido confortáveis durante a permanência em cada uma das posições. Conclusão: No posicionamento prono, os padrões hemodinâmicos materno-fetais mantiveram-se dentro dos valores da normalidade. Na maca especialmente desenvolvida para gestantes, essa posição foi considerada segura e confortável / Introduction: Due to the increase of the abdominal volume, the prone position is a difficult and uncomfortable position for pregnant women. Hence, so far, it has not been tested if, in this position, a pregnant woman would have her maternal fetal hemodynamic parameters altered. Objectives: The objectives of this study were to analyze the influence of prone position in maternal-fetal hemodynamic parameters and the comfort of the pregnant woman on a prototype stretcher specially built for pregnant women. Method: A prospective, observational, crossover study with 30 pregnant women in antenatal segment, and 16 non pregnant women as a control group. The two groups were subdivided to take part in two types of randomized sequences of positions, investigating if the change in the order of the sequences would bring a significant alteration in the maternal fetal hemodynamic values. The positions used in this study were: prone, supine position, fowler position and left lateral. The following hemodynamic parameters were assessed: maternal heart rate, systolic blood pressure, diastolic blood pressure, oxygen saturation and respiratory rate and baseline and fetal variability. To the statistical analysis we used the non-parametric analysis for repeated measures and to verify if the position prior to the prone position would have any influence in it and variables of variation were created and compared to the Wilcoxon test. Results: Comparing the prone positions indexes to the other ones obtained, we observed that all the parameters were within the standards of normality and there was no interference in positions prior to the prone position in these values. The pregnant group showed means significantly higher than the ones of the non-pregnant women regarding the heart rate in sequence 1 (p < 0.004) and in sequence 2 (p < 0.001) and respiratory rate in sequence 1 (p= 0.041) and sequence 2 (p= 0.012). In the analysis of the pregnant group we observed that in prone position the systolic blood pressure and the diastolic blood pressure showed lower values than the other in both sequences. In the systolic blood pressure in the pregnant group sequence 1 the comparison of prone position with the fowler position (p < 0.001), with the supine position (p < 0.001) and with the left lateral (p < 0.001) in the pregnant group sequence 2 the comparison of the prone position with the fowler position (p < 0.001) and with the supine position (p= 0.013) it is observed a significant difference. In the diastolic blood pressure in comparison of the prone position in the pregnant group sequence 1 with the fowler position (p < 0.006), with supine position (p= 0.023) and with the left lateral (p= 0.017) and the pregnant group sequence 2 with the fowler position (p < 0.005) and with the supine position (p= 0.008) it is observed a significant difference. To the oxygen saturation in the pregnant group sequence 2 there was a significant difference when compared to the prone position with the fowler position (p= 0.021) and the prone position with the supine position (p= 0.003). In both sequences there were no significant differences in the fetal baseline between prone position with the left lateral. There were not observed any significant variations in the fetal variability in the sequences assessed. All the patients declared having felt comfortable during their stay in each one of the positions. Conclusion: In the prone positioning the maternal-fetal hemodynamic parameters were within the standards of normality and this position on the stretcher especially designed for pregnant women, considered as a safe and comfortable position

Foram utilizados vinte ovinos, machos com idade entre um e três anos, com peso médio de 33,1 ± 3,1 kg. Os animais foram distribuídos de forma aleatória em três grupos, designados como GH (halotano), GI (isofluorano) e GS (sevofluorano) em experimento do tipo cruzado com intervalo mínimo de 1 semana entre os tratamentos. Numa primeira etapa, os animais foram anestesiados com auxílio de máscara facial, intubados e mantidos sob anestesia com agente segundo a determinação de cada grupo e obtida a concentração alveolar mínima (CAM) dos agentes por meio de estímulo nociceptivo com eletroestimulação. Em uma segunda etapa, os animais foram mantidos com a CAM previamente compreendendo os momentos de M0 a M8 com intervalo de 15 minutos entre os mesmo. Foram avaliadas as funções hemodinâmicas, respiratórias, hemogasométricas, endócrinas e o índice biespectral. Os valores médios de CAM foram de 0,71 ± 0,09%, 1,31 ± 0,33% e 2,69 ± 0,29% para o halotano, isofluorano e sevofluorano respectivamente. Houve redução dos valores do índice cardíaco no GI em todos os momentos comparativamente ao basal (p<0,001); na comparação entre os grupos os valores do M0 no GI foram superiores aos verificados em GH e GS (p<0,01). O valores do volume e índice sistólico foram inferiores ao basal a partir de M6 no grupo GH (p<0,05) e no GI todos os momentos foram inferiores ao basal (p<0,001); na comparação entre os grupos verificou-se que os valores dessas variáveis no momento M0 no GI foram superiores a GH (p<0,05) e GS (p<0,001). As médias da pressão venosa central foram inferiores no grupo GH em todos os momentos comparativamente a M0 (p<0,001), e neste mesmo momento, as médias foram superioriores comparativamente aos outros grupos (p<0,05). Quanto ao índice de resistência vascular sistêmica, os valores foram superiores nos momentos M6, M3 e M7 nos grupos GH (p<0,05), GI (p<0,001) e GS (p<0,01), respectivamente; houve incremento do índice de resistência vascular periférica no momento M7 (p<0,01) no grupo GH a partir de M3 (p<0,001), em GI e em M7 e M8 (p<0,05) comparativamente ao basal. Os valores de tensão de dióxido de carbono no final da expiração foram superiores no grupo GH a partir de M4 (p<0,05) e no GI a partir de M3 (p<0,01) comparativamente ao basal. Os valores do índice biespectral no GI, foram superiores a partir de M5 em relação ao valor basal (p<0,01); na comparação entre os grupos, os momentos M2 e M3 foram inferiores no GI comparativamente ao GH e GS (p<0,05). Houve redução da temperatura retal em todos os grupos e momentos comparativamente ao valor basal (p<0,001). O período de recuperação foi superior no grupo GH (p<0,05). Nas condições do presente estudo a CAM em ovinos é de 0,71%, 1,31% e 2,69% para o halotano, isofluorano e sevofluorano respectivamente; os três agentes promovem redução do débito cardíaco e do volume sistólico; os valores do índice biespectral são semelhantes entre os fármacos, com valores inferiores quando tratados com isofluorano; há indução de estresse neuroendócrino avaliado por meio da dosagem de cortisol; os agentes promovem hipotermia tempo dependente; o halotano promove recuperação anestésica mais prolongada. / Twenty sheep, all males, were used in this experiment. Age ranged from one to three years and mean weight was 33.1 ± 3.1 kg. In a crossover design, animals were randomly treated with halothane (GH), isoflurane (GI) and sevoflurane (GS), with interval of 1 week between treatments. In a first phase, anesthesia was induced by facemask, animals were then intubated and anesthesia maintained with one of the three treatments. Minimum alveolar concentration (MAC) was obtained by nociceptive stimulation for each animal. In phase 2, the animals were anesthetized again by facemask and maintained at the predetermined MAC (Phase 1) for two hours. Data was collected at moments (M0-M8) with intervals of 15 minutes. Cardiovascular, respiratory and bispectral index parameters were recorded. Blood gas analysis, CBC and cortisol levels were also measured and recorded. MAC of each group were 0.71± 0.09%, 1.31 ± 0.33% e 2.69 ± 0.29% for GH, GI and GS respectively. There was a reduction in cardiac index in GI at all times compared to baseline (p<0.001). Among groups the values of M0 in GI were higher than those in GH and GS (p<0.01). In GH, the end systolic volume and stroke index were lower than baseline from M6 until the end of the experiment (p<0.05). In GI, ESV and SI were below the baseline at all times (p<0.001). Among groups it was found that the GI baseline values of these variables were higher than GH (p<0.05) and GS (p<0.001). The mean central venous pressure were lower in the GH group at all times compared to M0 (p<0.001), which was higher than the baseline of the other groups (p<0.05). When compared to baseline, systemic vascular resistance index was higher in the moments M6, M3 and M7 in GH (p<0.05), GI (p<0.001) and GS (p<0.01), respectively. There was an increase in peripheral vascular resistance index (PVRI) at the time M7 (p<0.01) in GH from M3 to the end of the study (p<0.001). In GI, PVRI was increased at M7 and M8 (p<0.05) in comparison to baseline. The values of end-tidal of carbon dioxide were higher than baseline in the GH group from M4 (p<0.05) until the end of study. The same occurred in GI starting at M3 (p<0.01). In GI, the bispectral index values were higher starting at M5 to the end when compared to baseline (p<0.01). Among groups, BIS was lower at M2 and M3 in GI when compared to GH and GS (p< 0.05). Rectal temperature decreased in all groups at all moments in comparison to baseline (p<0.001). The recovery period was longer in GH (p<0.05). Under this study conditions MAC in sheep were 0.71%, 1.31% and 2.69% for halothane, isoflurane and sevoflurane, respectively. All treatments further reduced cardiac output and stroke volume; bispectral index values were similar among drugs, with lower values when treated with isoflurane. A stress response was believed to be induced due to elevation of serum cortisol in all groups. These inhalants promote time-dependent hypothermia. Halothane anesthesia promotes prolonged recovery.

RESUMO Castilho Junior, O T. Avaliaço do efeito da meia elástica na hemodinâmica venosa dos membros inferiores de corredores. 2015. 71f. Dissertação (Mestrado) - Faculdade de Medicina Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto - SP. Introdução: A literatura médica a respeito da eficácia e dos benefícios do uso de meias elásticas de compressão graduada (MECG) na corrida é controversa e inconclusiva. Objetivo: O objetivo foi verificar as alterações da hemodinâmica venosa dos MMII pela pletismografia a ar (PGA) , do lactato sanguíneo e da resposta clínica provocadas pela corrida em atletas amadores saudáveis sem e com o uso de MECG. População e Método: Dez atletas (4 homens e 6 mulheres), corredores voluntários, com idade média 40,3 anos, índice de massa corporal (IMC) médio de 21,88, foram submetidos a avaliações de parâmetros hemodinâmicos venosos por meio da PGA (IEV-índice de enchimento venoso; FE-fraço de ejeção e FVR-fração de volume residual), dosagem de lactato capilar e avaliação clínica (frequência cardíaca, dor e conforto nos MMII) em 3 situações: em repouso (antes da corrida); logo depois de uma corrida de 10 km em esteira com inclinação de 1% sem o uso de MECG e uma semana após com o uso de MECG. Todas as variáveis foram analisadas estatisticamente e considerou-se 5% o nível de significância. Resultado: Após a corrida houve elevação significativa dos valores de IEV dos MMII no grupo sem em relação ao grupo com MECG e em repouso. Houve queda significativa da FVR do membro inferior direito no grupo com MECG em relação aos grupos em repouso e sem meia elástica, o que não ocorreu no membro inferior esquerdo. A FE foi semelhante em todas as situações. O lactato elevou-se no final da corrida no grupo sem MECG e notou-se tendência a elevação no grupo com MECG, mas a diferença inicial e final do lactato nas duas situações permaneceu semelhante. As manifestações clínicas (frequência cardíaca , dor, conforto e lesões) foram semelhantes em todas as situações após a corrida sem e com MECG. Conclusão: Apesar de inalteradas as manifestações clínicas ( frequência cardíaca, dor e desconforto) e dos níveis de lactato de corredores amadores, sadios, após a corrida de 10km com inclinação de 1%, o uso de MECG teve efeitos positivos na hemodinâmica venosa dos MMII, aferidos pela PGA e caracterizados pela redução do IEV em ambos os membros e pela queda da FVR, pelo menos no membro inferior direito. / Background: The literature about the efficacy and the benefits of wearing compression stockings (CS) in running is controverse and inconclusive. Objective: The objective was to verify the changes of venous hemodynamic parameters of the lower limbs measured by air pletismography (APG), of the capillary lactate and of some clinical aspects promoted by running in normal healthy runners wearing or not compression stockings. Methods: Ten volunteer runners (4 men, 6 women), mean age 40,3 years, mean corporal mass index of 21,88, were submitted to evaluation the hemodynamic parameters measured by APG (venous filling index VFI; ejection fraction EF and residual venous fraction - RVF), measurement of capillary lactate and clinical aspects (cardiac frequency, pain, comfort and lesions) in 3 situations: at rest (before running); after a 10 Km running on a treadmill with 1% inclination degree without CS and a week later, after the same running wearing compression stockings. All variables were statistically analised and it was considered 5% as the significance level. Results: After running there was significant elevation of the VFI in the group without CS compared to the groups at rest and with CS. There was also a meaning descent of the RVF levels of the right lower limb of the volunteers wearing CS compared to those without CS and at rest, but this was not noticed on the left lower limb. The EF was the same in all situations. The lactate levels increased after running without CS and there was a tendency of elevation with the use of CS, but the initial and final differences in both situations remained the same. The clinical aspects (cardiac frequency, pain, comfort and lesions) were similar after running with or without CS. Conclusion: Although there were no changes of the clinical aspects (cardiac frequency, pain, comfort and lesions) and the lactate levels of healthy amateur runners after a 10 Km running on a treadmill with a 1% elevation degree, APG showed that the use of CS promoted beneficial effects on venous hemodynamics of the lower limbs, featured by the fall of the VFI levels on both lower limbs and the fall of the RVF levels on the right lower limbs.

Since the advent of functional magnetic resonance imaging (fMRI) and the rise in popularity of its use for resting state functional connectivity mapping (rs-FCM) to non-invasively detect correlated networks of brain activity in human and animal models, many resting state FCM studies have reported differences in these networks under pathologies such as Alzheimer’s or schizophrenia, highlighting the potential for the method’s diagnostic relevance. A common underlying assumption of this analysis, however, is that the blood oxygen level dependent (BOLD) signal of fMRI is a direct measurement of local neural activity. The BOLD signal is in fact a measurement of the local changes in concentration of deoxy-hemoglobin (HbR). Thus, it is imperative that neurovascular coupling—the relationship between neuronal activity and subsequent hemodynamic activity—be better characterized to enable accurate interpretation of resting state fMRI in the context of clinical usage. This dissertation first describes the development and utility of WFOM paradigm for the robust and easily adaptable imaging of simultaneous neuronal and hemodynamic activity in awake mouse models of health or disease in strains with genetically encoded fluorescent calcium reporters. Subsequent exploration of resting state WFOM data collected in Thy1-GCaMP3 and Thy1-GCaMP6f mouse strains is then presented, namely the characterization of spatiotemporal patterns of neuronal and hemodynamic activity and different modulatory depths of neuronal activity via a toolbox of unsupervised blind source separation (e.g. k-means clustering) and supervised (e.g. non-negative least squares, Pearson correlation) analysis tools. The presence of these different modulatory depths of neuronal activity were then confirmed in another Thy1-jRGECO1a mouse strain using the same imaging scheme. Finally, the dissertation documents the application of the WFOM paradigm and select analysis tools to a novel mouse model of diffusely infiltrating glioma, through which neuronal and hemodynamic activity changes during diffusely infiltrating glioma development which impact temporal coherence of the tumor region activity relative to non-tumor regions activity were recorded and analyzed. The paradigm also allowed for recording of numerous spontaneous occurrences of interictal neuronal activity during which neurovascular coupling is modified in the tumor, as well as occurrences of non-convulsive generalized seizure activity (during which neurovascular is non-linear and cortex eventually suffers hypoxia). The detection of spatiotemporal patterns and different modulatory depths of activity in the awake mouse cortex, as well as observation of changes in functional activity in the context of diffusely infiltrating glioma, provide us with new insights into the possible mechanisms underlying variations in resting state connectivity networks found in resting state fMRI studies comparing health and disease states.

Hipercapnia, hipóxia e atelectasia pulmonar são eventos comuns em pacientes anestesiados. A ventilação mecânica pode ser usada nesses casos para garantir adequada troca de gases dos pacientes e melhora da oxigenação, porém seu uso implica em efeitos hemodinâmicos e pulmonares indesejáveis. Para minimizar estes, baixos valores volumes correntes são recomendados, além do uso de pressão positiva ao final da expiração (PEEP) e manobras de recrutamento alveolar (MRA). Este estudo intencionou avaliar o uso de volume corrente de 8mL/kg, além do uso de PEEP associada, ou não, a MRA quanto a oxigenação e troca gasosa de cães jovens, ASA I e II, submetidos a anestesia geral inalatória, para cirurgias ortopédicas e odontológicas, durante 1 hora e que permaneceram em decúbito dorsal. Para tanto, foram utilizados 27 cães, divididos em 2 grupos (14 no grupo PEEP e 13 no grupo MRA) de acordo com o uso isolado de PEEP ou associado a MRA. Todos os pacientes receberam acepromazina 0,03 mg/kg associada a meperidina 3 mg/kg (IM) como MPA, indução realizada com propofol em dose suficiente para intubação orotraqueal e manutenção realizada com isoflurano 1,0 a 1,6% em FiO2 de 50%. Todos os cães foram mantidos em decúbito dorsal logo após intubação, instituição do protocolo de ventilação determinado de acordo com o grupo em que foi alocado e uso de bloqueador neuromuscular rocurônio na dose de 0,6 mg/kg (IV). Após 15 minutos de instrumentação e estabilização do plano anestésico os dados de mecânica ventilatória, gasometria arterial, oxigenação e hemodinâmica foram coletados (M0). No grupo em que se realizou MRA, a PEEP saiu de 0, sofrendo acréscimos de 5 cmH2O a cada 3 minutos, chegando a 15 e retornando gradativamente a 5 cmH2O, pressão na qual foi mantido durante o resto do tempo anestésico. No grupo PEEP foi instituída a pressão de 5 cmH2O, sendo mantida até a extubação. Ao final da MRA (M15 15 minutos após M0) todos foram novamente coletados, assim como em M30 e M60 (respectivamente, 30 e 60 minutos após M15). Através dos parâmetros de capnometria, observou-se que o volume corrente utilizado foi eficiente para garantir troca gasosa em todos os pacientes incluídos no estudo. O uso da MRA foi suficiente para reabrir as áreas colapsadas do pulmão em M0, porém, quando comparado seus índices de oxigenação e complacência com aqueles encontrados no grupo PEEP, não houve superioridade de um dos grupos. O uso de PEEP 5 cmH2O foi capaz de manter os alvéolos sem sofrer re- colapso ao longo do período do estudo. O uso de MRA ou PEEP não interferiu nos parâmetros de hemodinâmica dos cães inseridos no estudo. / Hypercapnia, hypoxia and pulmonary atelectasis are common events in anesthetized patients. Mechanical ventilation can be used in these cases to ensure adequate gas exchange of patients and improvement of oxygenation, but its use implies undesirable hemodynamic and pulmonary effects. To minimize these, low tidal volumes are recommended, in addition to the use of positive end-expiratory pressure (PEEP) and alveolar recruitment maneuvers (ARMs). The aim of this study was to evaluate the use of current volume of 8mL / kg, in addition to the use of PEEP, associated to oxygenation and gas exchange of young dogs, ASA I and II, submitted to general inhalation anesthesia for orthopedic surgeries and dental implants for 1 hour and remained in the supine position. For this, 27 dogs were used, divided into 2 groups (14 in the PEEP group and 13 in the ARM group) according to the use of PEEP alone or associated with ARM. All patients received acepromazine 0.03 mg / kg associated with meperidine 3 mg / kg (IM) as MPA, induction with propofol in sufficient doses for orotracheal intubation and maintenance with isoflurane 1.0 to 1.6% in FiO2 of 50%. All dogs were kept in dorsal decubitus position immediately after intubation, ventilation protocol established according to the group in which they were allocated and use of neuromuscular blocker rocuronium at the dose of 0.6 mg / kg (IV). After 15 minutes of instrumentation and stabilization of the anesthetic plane the data of ventilatory mechanics, arterial blood gases, oxygenation and hemodynamics were collected (M0). In the group which was held MRA left PEEP 0, 5 cmH2O suffering increases every 3 minutes, reaching 15 and returning gradually to 5 cmH 2 O, in which pressure was maintained for the rest of the duration of anesthesia. In the PEEP group, a pressure of 5 cmH2O was instituted and maintained until extubation. At the end of the ARM (M15 - 15 minutes after M0) all were collected again, as well as in M30 and M60 (respectively, 30 and 60 minutes after M15). Through the parameters of capnometry, it was observed that the tidal volume used was efficient to guarantee gas exchange in all patients included in the study. The use of MRA was enough to reopen the collapsed lung areas M0, but compared their levels of oxygenation and compliance with those found in the PEEP group, there was no superiority of one group. The use of PEEP 5 cmH2O was able to maintain the alveoli without undergoing re-collapse over the study period. The use of MRA or PEEP did not interfere in the hemodynamic parameters of the dogs inserted in the study.

Laboratory tests are a primary resource for diagnosing patient diseases. However, physicians often make decisions based on a single laboratory result and have a limited perspective of the role of commonly-measured parameters in enhancing the diagnostic process. By providing a dynamic patient profile, the diagnosis could be more accurate and timely, allowing physicians to anticipate changes in the recovery trajectory and intervene more effectively. The assessment and monitoring of the circulatory system is essential for patients in intensive care units (ICU). One component of this system is the platelet count, which is used in assessing blood clotting. However, platelet counts represent a dynamic equilibrium of many simultaneous processes, including altered capillary permeability, inflammatory cascades (sepsis), and the coagulation process. To characterize the value of dynamic changes in platelet count, analytical methods are applied to datasets of critically-ill patients in (1) a homogeneous population of ICU cardiac surgery patients and (2) a heterogeneous group of ICU patients with different conditions and several hospital admissions. The objective of this study was to develop a methodology to anticipate adverse events using metrics that capture dynamic changes of platelet counts in a homogeneous population, then redefine the methodology for a more heterogeneous and complex dataset. The methodology was extended to analyze other important physiological parameters of the circulatory system (i.e., calcium, albumin, anion gap, and total carbon dioxide). Finally, the methodology was applied to simultaneously analyze some parameters enhancing the predictive power of various models. This methodology assesses dynamic changes of clinical parameters for a heterogeneous population of ICU patients, defining rates of change determined by multiple point regression and by the simpler fixed time parameter value ratios at specific time intervals. Both metrics provide prognostic information, differentiating survivors from non-survivors and have demonstrated being more predictive than complex metrics and risk assessment scores with greater dimensionality. The goal was to determine a minimal set of biomarkers that would better assist care providers in assessing the risk of complications, allowing them alterations in the management of patients. These metrics should be simple and their implementation would be feasible in any environment and under uncertain conditions of the specific diagnosis and the onset of an acute event that causes a patient's admission to the ICU. The results provide evidence of the different behaviors of physiologic parameters during the recovery processes for survivors and non-survivors. These differences were observed during the first 8 to 10 days after a patient's admission to the ICU. The application of the presented methodology could enhance physicians' ability to diagnose more accurately, anticipate changes in recovery trajectories, and prescribe effective treatment, leading to more personalized care and reduced mortality rates.

Nailfold capillary microscopy is simple, non-invasive, no injuries and easy to observe human`s microcirculation and micro blood stream directly. Due to these advantages, it plays a significant role in diseases diagnoses, treatments and prognosis. The observation of microcirculation focuses on hand, foot naildfold, conjunctival, lingual surface and lips. Nailfold microcirculation is usually performed on the ring finger. However, when measuring the speed of blood flow, difficulty to stabilize the region of interest (ROI) is often encountered. This problem becomes more serious when the magnification of microscope increases. Fixture to stabilize finger will inevitably affect the speed of blood flow under observation. The Laser Doppler blood flow velocimetry method, is expensive, only can be used in bigger capillary or to measure the average flow velocity of lager observed area, lacking of diversified morphological features of capillary, it¡¦s precision is worse than microscopy image capture method, and because of the regular contraction and relaxation of arterioles it can only measure the local blood flow velocity, cannot describe whole details of capillary blood flow velocity, some important information of microcirculation will be ignored easily. This thesis employs computer vision technique to operate displacement compensation of microscopy image sequence to stabilize observed area and extract area of capillary. Then the morphological and hemodynamic pathology features will be derived and analyzed to evaluate the status of a person¡¦s health. Not only morphological features, e.g., length, density and color, but also hemodynamic features, e.g., blood flow velocity will be measured to assess the microcirculation in end capillary. The most significant characteristic of this project is to combine three-dimensional models reconstruction technology of computer graphic to reconstruct three-dimensional capillary models and perform the three-dimensional dynamic blood flow visualization. Thus, the capillary blood flow can be adjusted and observed in the desired orientation, magnification and viewpoint. A variety of pathologically significant features of nailfold microcirculation will be extracted in the project proposed. These features can be classified into morphological and hemodynamic features. The morphological features extracted include the number, width/height, density, arteriolar limb caliber, curved segment caliber, venular limb caliber, blood color, tortuosity, and width of the curved segment of capillaries. On the other hand, hemodynamic features including velocity, direction of blood flow will also be extracted. By integrating both morphological and hemodynamic features, the status of a person¡¦s health can be evaluated by the doctor. The novel system proposed is not only easy to operate, low-cost but also has the great potential to be utilized clinically.