Este trabalho teve como objetivo avaliar os efeitos sistêmicos, microcirculatórios assim como mudanças na expressão gênica renal, causados pela ação da noradrenalina, nitropussiato de sódio e levosimendan no tratamento do choque hemorrágico. Nesse estudo foi utilizado o modelo da câmara dorsal.Os animais foram sujeitos a choque hemorrágico e após, foram aleatoriamente divididos em quatro grupos. Os grupos foram: CTRL, recebeu apenas ringer lactato; NPS recebeu ringer lactato com nitroprussiato de sódio; NA recebeu ringer lactato com noradrenalina e LEV, recebeu ringer lactato com levosimendan. Foram avaliados parâmetros sistêmicos, assim como parâmetros microcirculatórios (comparados como percentual em relação ao momento basal). Além disso, foi avaliada a expressão gênica renal de eNOS, HIF-1α, ICAM e caspase-3. O grupo NPS apresentou uma recuperação sustentada do diâmetro arteriolar ( 89 12 %) e DCF (125 114 %) ao final do tratamento. Houve recuperação da velocidade de hemácias nos grupos CTRL e NPS. Não houve diferença em relação ao número de leucócitos aderidos e/ou rolantes ao final do tratamento. A expressão gênica renal de eNOS e caspase-3 entre os grupos não apontou diferenças, entretanto houve diferença significativa na expressão renal de HIF- 1α no grupo NA (0,65 0,08, UA) em relação ao grupo CTRL (0,44 0,06, UA) e LEV (0,45 0,06, UA). Todos os grupos tiveram uma maior expressão de ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, UA) em relação ao grupo SHAM (0,50 0,05, UA). Ringer lactato puro ou associado com noradrenalina ou levosimendan não foram suficientes para recuperar e sustentar os parâmetros microvasculares. O tratamento com nitroprussiato de sódio foi o que apresentou os melhores resultados, com recuperação dos diâmetros arteriolar, da DCF e velocidade de hemácias. / This work aimed at evaluating the systemic and microcirculatory effects, as well as changes in renal gene expression elicited by noradrenalin, sodium nitroprusside and levosimendan associated to volume resuscitation in the treatment of hemorrhagic shock. The dorsal chamber model was used in this study. Animals were subjected to hemorrhagic shock and after that, were randomly distributed between four groups. Groups were: CTRL, received only lactated ringer's solution; NPS received lactated ringer's solution with sodium nitroprusside; NA received lactated ringer's solution with noradrenaline and LEV received lactated ringer's with levosimendan. Systemic and microcirculatory parameters were evaluated ( as percent change compared to baseline). Furthermore, renal genic expression of eNOS, HIF-1a and caspase-3 were also evaluated. NPS group presented a sustained recovery of arteriolar diameter ( 89 12 %) and FCD (125 114 %) at the end of the treatment. There was a red blood cell velocity recovery in CTRL and NPS groups. There was no difference regarding adhered or rolling leukocytes at the end of the treatment. eNOS and caspase-3 renal genic expression between groups showed no differences, however, there was a significant difference in renal genic expression of HIF-1α in NA group (0,65 0,08, AU) compared to CTRL (0,44 0,06, AU) e LEV (0,45 0,06, AU). All groups had a higher expression of ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, AU) compared to the SHAM group (0,50 0,05, AU). Ringer's lactate solution associated or not to noradrenaline or levosimendan were not enough to recover and sustain microvascular parameters. Treatment with sodium nitroprusside presented the best results, with sustained arteriolar diameter, FCD and RBCV recoveries.

Este trabalho teve como objetivo avaliar os efeitos sistêmicos, microcirculatórios assim como mudanças na expressão gênica renal, causados pela ação da noradrenalina, nitropussiato de sódio e levosimendan no tratamento do choque hemorrágico. Nesse estudo foi utilizado o modelo da câmara dorsal.Os animais foram sujeitos a choque hemorrágico e após, foram aleatoriamente divididos em quatro grupos. Os grupos foram: CTRL, recebeu apenas ringer lactato; NPS recebeu ringer lactato com nitroprussiato de sódio; NA recebeu ringer lactato com noradrenalina e LEV, recebeu ringer lactato com levosimendan. Foram avaliados parâmetros sistêmicos, assim como parâmetros microcirculatórios (comparados como percentual em relação ao momento basal). Além disso, foi avaliada a expressão gênica renal de eNOS, HIF-1α, ICAM e caspase-3. O grupo NPS apresentou uma recuperação sustentada do diâmetro arteriolar ( 89 12 %) e DCF (125 114 %) ao final do tratamento. Houve recuperação da velocidade de hemácias nos grupos CTRL e NPS. Não houve diferença em relação ao número de leucócitos aderidos e/ou rolantes ao final do tratamento. A expressão gênica renal de eNOS e caspase-3 entre os grupos não apontou diferenças, entretanto houve diferença significativa na expressão renal de HIF- 1α no grupo NA (0,65 0,08, UA) em relação ao grupo CTRL (0,44 0,06, UA) e LEV (0,45 0,06, UA). Todos os grupos tiveram uma maior expressão de ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, UA) em relação ao grupo SHAM (0,50 0,05, UA). Ringer lactato puro ou associado com noradrenalina ou levosimendan não foram suficientes para recuperar e sustentar os parâmetros microvasculares. O tratamento com nitroprussiato de sódio foi o que apresentou os melhores resultados, com recuperação dos diâmetros arteriolar, da DCF e velocidade de hemácias. / This work aimed at evaluating the systemic and microcirculatory effects, as well as changes in renal gene expression elicited by noradrenalin, sodium nitroprusside and levosimendan associated to volume resuscitation in the treatment of hemorrhagic shock. The dorsal chamber model was used in this study. Animals were subjected to hemorrhagic shock and after that, were randomly distributed between four groups. Groups were: CTRL, received only lactated ringer's solution; NPS received lactated ringer's solution with sodium nitroprusside; NA received lactated ringer's solution with noradrenaline and LEV received lactated ringer's with levosimendan. Systemic and microcirculatory parameters were evaluated ( as percent change compared to baseline). Furthermore, renal genic expression of eNOS, HIF-1a and caspase-3 were also evaluated. NPS group presented a sustained recovery of arteriolar diameter ( 89 12 %) and FCD (125 114 %) at the end of the treatment. There was a red blood cell velocity recovery in CTRL and NPS groups. There was no difference regarding adhered or rolling leukocytes at the end of the treatment. eNOS and caspase-3 renal genic expression between groups showed no differences, however, there was a significant difference in renal genic expression of HIF-1α in NA group (0,65 0,08, AU) compared to CTRL (0,44 0,06, AU) e LEV (0,45 0,06, AU). All groups had a higher expression of ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, AU) compared to the SHAM group (0,50 0,05, AU). Ringer's lactate solution associated or not to noradrenaline or levosimendan were not enough to recover and sustain microvascular parameters. Treatment with sodium nitroprusside presented the best results, with sustained arteriolar diameter, FCD and RBCV recoveries.

In a mouse model of pulmonary thromboembolism induced by a collagen-adrenaline mixture, the SFE extract and ligustilide reduced the paralysis-death ratio, and the anti-thrombotic response of senkyunolide A was more pronounced. The effect of BDPH was not significant. Neither the SFE extract nor the three phthalides prolonged bleeding time in tail-transected mice. / In a rat myocardial ischemia-reperfusion model involving coronary artery ligation, 7-day pre-treatment with the SFE extract and ligustilide reduced ventricular arrhythmias in isolated hearts. BDPH and senkyunolide A were without significant effects. / In rat platelet-rich plasma, platelet aggregation induced by collagen and U46619 but not by adenosine diphosphate was inhibited by the SFE extract. Ligustilide inhibited the responses of all three agonists, while BDPH and senkyunolide A inhibited the collagen response only. / Raw Rhizoma Chuanxiong herb and its crude extract as obtained by supercritical fluid extraction (SFE) comprised mainly phthalides. The SFE extract and three representative phthalides, butylidenephthalide (BDPH), ligustilide and senkyunolide A, were studied on vasorelaxation, myocardial ischemia, platelet aggregation and thrombosis. The mechanisms underlying BDPH-mediated vasorelaxation were also explored. / Rhizoma Chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort., is a common traditional Chinese medicine used for the treatment of cardiovascular diseases. Surprisingly, the scientific basis of its action is poorly understood. The current study aims to establish the pharmacological basis of the cardiovascular effects of Rhizoma Chuanxiong and its active constituents by examining their effects in several cardiovascular domains. / The current study demonstrated various cardiovascular actions of Rhizoma Chuanxiong, and thereby established the pharmacological basis of the effects of the herb. Phthalides, in particular BDPH, ligustilide and senkyunolide A, were important contributors to such actions. Future investigation of the SFE extract and/or individual phthalides related to the progression from in vitro and in vivo effectiveness to clinical efficacy is much anticipated. / The SFE extract, BDPH, ligustilide and senkyunolide A produced vasorelaxation on isolated preparations of rat aorta, rat saphenous vein and pig coronary artery. BDPH-mediated relaxation appeared to involve both extracellular Ca 2+-dependent (L-type voltage-operated, receptor-operated and store-operated Ca2+ channels) and independent (NO modulation, Ca2+ release from internal stores and Ca2+ desensitization) mechanisms. BDPH was also observed to augment relaxation induced by sodium nitroprusside and forskolin through mechanisms that remain undefined. / Chan Sun Kin Sunny. / "July 2005." / Advisers: G. Lin; R. L. Jones. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1575. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 190-209). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

University of Macau / Institute of Chinese Medical Sciences

Systemic cardiovascular effects of volatile and intravenous anesthetics :evaluation in the time domain, the frequency domain and the pressure-volume plane.<p>Cardiovascular stability is of prime importance in order to maintain homeostasis during anesthesia and intensive care, and to reduce cardiovascular perioperative morbidity and mortality.<p>General anesthesia does have profound cardiovascular effects, and the end result is usually a decrease in arterial pressure, with the potential of inadequate organ perfusion and consequently organ damage. Therefore, elucidation of the mechanisms of cardiovascular effects of general anesthesia is important in order to prevent and/or to treat adequately the cardiovascular perturbations, and to perform the optimal choice of the anesthetic management. Anesthetic management for the patient presenting with cardiovascular alterations relates essentially to the question of a volatile anesthetic based regimen versus a propofol based anesthetic regimen.<p>A traditional hemodynamic investigation includes the measurement of heart rate, systemic and pulmonary arterial pressure, the filling pressures of the heart and cardiac output. These measurements allows for the calculation of systemic vascular resistance in order to evaluate arterial tone. However, calculated systemic vascular resistance cannot discriminate between passive (flow-dependent) and active (tone-dependent) changes in arterial pressure. Changes in arterial tone must be assessed by constructing pressure-flow plots.<p>Neither calculated systemic vascular resistance nor pressure-flow plots takes into account the pulsatile nature of the circulation. In order to do so, one has to measure instantaneous pressure and flow waves, perform harmonic analysis on both waves and calculate vascular impedance spectra.<p>The cardiovascular system is a mechanical system in which two components are functionally coupled: there is an energy transfer between the energy source, i.e. the left ventricle, and its mechanical load, i.e. the arterial tree. An alteration in one of these components necessitates an appropriate alteration in the other component in order to maintain optimal coupling, i.e. maximal energy transfer between the two elements. In the pressure-volume plane the left ventricle and the arterial tree are considered to be two elastic chambers in series. The performance of the left ventricle is quantified by the end-systolic elastance, while the load of the arterial tree is quantified by the effective arterial elastance. The ratio of end-systolic elastance to effective arterial elastance relates ventricular-arterial coupling to either maximisation of stroke work or either to maximisation of mechanical efficiency (i.e. the ratio of mechanical power output to cardiac oxygen consumption).<p>In the first experiment we investigated the systemic vascular effects of isoflurane versus propofol anesthesia in dogs using a traditional hemodymamic approach, measurement of instantaneous aortic flow and pressure with subsequent calculation of aortic input impedance spectra, and construction of pressure-flow plots generated by gradual reduction of venous return. Calculated systemic vascular resistance could not detect differences in arteriolar tone between isoflurane and propofol, whereas pressure-flow plots did: compared with isoflurane, propofol better maintained aortic pressure at all levels of flow, except at the lowest level of flow. Impedance spectra demonstrated a decreased pulsatile load and less energy losses in pulsations with propofol as compared with isoflurane.<p>In the second experiment we investigated the effects of escalating doses of sevoflurane and propofol anesthesia on arterial mechanical properties and left ventricular-arterial coupling in the dog. Arterial mechanics were assessed by traditional hemodynamics, aortic input impedance spectra, and pressure-flow plots generated by rapid caval inflow reduction. Left ventricular-arterial coupling was assessed as the ratio of end-systolic elastance to effective arterial elastance. The end-systolic elastance and the effective arterial elastance were obtained from left ventricular pressure and aortic flow data using a ‘single-beat’ estimation method. Traditional hemodynamics and pressure-flow plots demonstrated that sevoflurane causes a limited arteriolar vasodilation and causes arterial hypotension essentially by a decrease of cardiac output. Propofol insignificantly decreases cardiac output, but is an “actual” arteriolar dilator. The impedance spectra demonstrated that sevoflurane and propofol do have different effects on the elastic properties of large conduit arteries. Sevoflurane increased the characteristic impedance and reduced arterial compliance, indicating an increased physical elastance of the arterial tree. Propofol caused an insignificant increase of the characteristic impedance and the arterial compliance remained unaltered, suggesting that propofol does have a beneficial effect on the elastic properties of the arterial tree, thereby confirming the conclusion of the first experiment (i.e. a decreased pulsatile load with propofol). Sevoflurane impaired ventricular-arterial coupling by decreasing end-systolic elastance and increasing effective arterial elastance. Propofol maintained left ventricular-arterial coupling: the end-systolic elastance and effective arterial elastance remained unchanged and as consequence the ratio of end-systolic elastance to effective arterial elastance did not change. All results taken together we conclude that sevoflurane decreases cardiac output and left ventricular contractility, and increases the pulsatile and total load to the left ventricle. Propofol maintains cardiac output and left ventricular contractility, induces an arterial dilatation but without affecting the pulsatile and total load to the left ventricle.<p>These results, obtained in dogs, suggest that propofol, compared to volatile anesthetics, is an anesthetic, which can better preserve hemodynamic stability and homeostasis in the cardiovascular compromized patient undergoing surgery.<p>/<p>Evaluation des effets cardiovasculaires systémiques des agents anesthésiques dans le domaine du temps, le domaine de la fréquence et le plan pression-volume.<p>La stabilité cardiovasculaire est d’une importance prioritaire pour maintenir l’homéostasie pendant l’anesthésie et le séjour aux soins intensifs, et pour réduire la morbidité et mortalité cardiovasculaire pendant la période péri-opératoire.<p>L’anesthésie générale exerce des effets marqués sur le système cardiovasculaire. Généralement une hypotension artérielle systémique est observée, avec la possibilité d’une hypoperfusion des organes vitaux et ultérieurement des lésions de ces mêmes organes. Donc l’éclaircissement des mécanismes des effets cardiovasculaires de l’anesthésie générale est important pour prévenir et traiter les perturbations cardiovasculaires, et pour effectuer le choix optimal de la gestion anesthésique.<p>La question de la gestion anesthésique chez le patient présentant une fonction cardiovasculaire altérée se traduit essentiellement par le choix de l’anesthésie soit basée sur un agent volatile soit basée sur le propofol intraveineux.<p>Une exploration traditionnelle de l’hémodynamique comprend le mesure de la fréquence cardiaque, des pressions artérielles systémique et pulmonaire, des pressions de remplissage et du débit cardiaque. Ces mesures permettent de calculer la résistance vasculaire systémique de manière à évaluer le tonus artériel. Cela dit, la résistance vasculaire systémique calculée ne peut pas faire la différence entre des changements actifs (changements du tonus artériel) ou passifs (changements des débits) de la pression artérielle systémique. Les changements du tonus artériel doivent être évalués par des courbes pression - débit.<p>Ni les résistances vasculaires systémiques ni les courbes pression débit ne tiennent compte de la nature pulsatile de la circulation. L’exploration des effets pulsatiles<p>requiert tout d’abord la mesure des pressions instantanées et des débits instantanés. En seconde lieu, ces signaux doivent subir une décomposition harmonique (analyse de Fourier), pour afin de pouvoir calculer le spectre d’impédance vasculaire.<p>Le ventricule gauche et le système artériel sont deux éléments d’un système mécanique, dans lesquels il y a un transfert d’énergie entre la source d’énergie et sa charge. Une modification dans un des éléments nécessite une modification appropriée dans l’autre élément pour maintenir un couplage optimal entre les deux éléments, c'est-à-dire un transfert maximal d’énergie. Dans le plan pression volume, le ventricule gauche et l’arbre artériel sont considérés comme deux chambres élastiques en série.<p>La performance du ventricule gauche est quantifiée par l’élastance ventriculaire télésystolique, et la charge du système artériel est quantifiée par l’élastance artérielle effective. Le rapport entre l’élastance ventriculaire télésystolique et l’élastance artérielle effective permet de situer le « couplage ventriculo-artériel » soit en termes de maximisation du travail ventriculaire ou soit en termes d’ efficience mécanique. L’efficience myocardique est définie comme un rapport entre la puissance ventriculaire produite et l’oxygène consommé.<p>Dans la première expérimentation, nous avons étudié les effets vasculaires sur la circulation systémique du chien d’une anesthésie inhalatoire à l’isoflurane versus une anesthésie au propofol, ceci au moyen d’une exploration hémodynamique traditionnelle, les spectres d’impédance aortique et les courbes pression débit étant générées par une réduction graduelle du retour veineux. Les résistances vasculaires systémiques calculées n’ont pas décelé de différences de tonus artériolaire entre les effets d’une anesthésie inhalatoire à l’isoflurane et les effets d’une anesthésie intraveineuse au propofol. Par contre les courbes pression-débit démontrent une différence :comparé à l’anesthésie à l’isoflurane, l’anesthésie au propofol maintientt mieux la pression aortique à tous les niveaux de débit sanguin sauf aux débits les plus bas. Les spectres d’impédance démontrent une charge pulsatile réduite et des pertes d’énergie réduites avec le propofol par rapport à l’isoflurane.<p>Dans la seconde expérimentation chez le chien, nous avons étudié les effets de doses croissantes de deux agents anesthésiques généraux, le sevoflurane et le propofol, sur les caractéristiques mécaniques du système artériel et le couplage ventriculo- artériel systémique. La mécanique artérielle était étudiée par une exploration hémodynamique traditionnelle, les spectres d’impédance aortique et les courbes pression-débit étant générées par une réduction rapide du retour veineux. Le couplage ventriculo-artériel systémique était calculé par le rapport entre l’élastance ventriculaire télésystolique et l’élastance artérielle effective. L’élastance ventriculaire télésystolique et l’élastance artérielle effective ont été estimées à partir de la pression ventriculaire gauche et du débit aortique instantané en appliquant une méthode dite de « single beat ». L’hémodynamique traditionnelle et les courbes pression - débit démontrent que le sevoflurane provoque une vasodilatation artériolaire limitée et que la cause principale de l’hypotension artérielle est une réduction du débit cardiaque. Le propofol réduit le débit cardiaque d’une manière non significative, mais est un vasodilatateur artériolaire réel. Les spectres d’impédance montrent que le sevoflurane et le propofol ont des effets différents sur les caractéristiques élastiques des grosses artères à conduction. Le sevoflurane augmente l’impédance caractéristique et réduit la compliance artérielle, indiquant une augmentation de l’élastance physique de l’arbre artériel. Le propofol provoque une augmentation non significative de l’impédance caractéristique, mais la compliance artérielle reste inchangée. Ces résultats suggèrent que le propofol aurait un effet favorable sur les propriétés élastiques de l’arbre artériel, et donc confirment les conclusions de la première expérimentation, c’est-à-dire une charge pulsatile réduite avec le propofol. Le sevoflurane dégrade le couplage ventriculo-artériel à la suite d’une réduction de l’élastance ventriculaire télésystolique et d’une augmentation de l’élastance artérielle effective. Le propofol maintient le couplage ventriculo-artériel. L’élastance ventriculaire télésystolique et l’élastance artérielle effective restent par contre inchangées. Par conséquent, le rapport entre les deux élastances ne change pas. Sur base de ces résultats, nous concluons que le sevoflurane réduit le débit cardiaque et la contractilité du ventricule gauche, et augmente la charge pulsatile et totale sur le ventricule gauche. Le propofol maintient le débit cardiaque et la contractilité du ventricule gauche, et induit une dilatation artérielle sans altérer la charge pulsatile et totale sur le ventricule gauche.<p>Ces résultats, obtenus chez le chien, suggèrent que le propofol, comparé aux anesthésiques volatiles, est un anesthésique qui permet de mieux préserver la stabilité hémodynamique et l’homéostasie chez le patient présentant une fonction cardiovasculaire restreinte et devant bénéficier d’un acte chirurgical.<p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished