L’Anévrisme de l’Aorte Abdominale (AAA) est une pathologie qui est définie par une dilatation localisée et permanente de l’artère et qui concerne plus de 8.8% des personnes âgées. Actuellement, lorsqu’un patient présente une dilatation de l’aorte impliquant l’éventualité d’une intervention chirurgicale en raison du risque de rupture, la décision thérapeutique est prise en fonction du rapport des diamètres de l’artère au niveau de l’anévrisme et à proximité de celui-ci. Pour déterminer ces diamètres, il est généralement procédé à un examen par imagerie médicale (Echographie, Tomographie, IRM,..). On constate cependant que le diagnostic ne peut pas se contenter d’une mesure dimensionnelle simple face aux risques induits: d’une part, passé une certaine excroissance, le risque de rupture peut atteindre 50% mais d’autre part plus de 5% des interventions chirurgicales provoquent le décès du patient. D’autres paramètres de mesure comme la compliance de l’artère, peuvent être à la base de la décision d’une intervention chirurgicale. La compliance correspond à une définition précise utilisée par les cardiologues : c’est une grandeur qui permet de caractériser l’aptitude à la déformation, décrivant la capacité de l'aorte à se distendre sous l'influence de la pression sanguine. De notre point de vue cette notion est insuffisante car, généralement, dans le cas d’un anévrisme, la rupture est très localisée du fait de la complexité de la forme de celui-ci. Il est donc nécessaire d’étendre sa définition à une grandeur localisée non pas au niveau d’une section mais à un endroit précis de la paroi. Les moyens de diagnostics seront d’autant plus fiables qu’ils pourront détecter la compliance localisée. De point de vue mécanique, la détermination de la compliance se transforme donc en la mesure de l'élasticité pariétale aortique localisée. L’élasticité n’est pas un paramètre mesurable directement. Donc, la problématique revient à la détermination de la déformation locale de la paroi aortique sous la sollicitation hémodynamique. La résolution de ce problème reste complexe. En effet, les sollicitations mécaniques dépendent de l’écoulement du sang, des organes environnants l’artère, des propriétés matérielles de l’artère et de la géométrie de l’anévrisme qui sont spécifiques à chaque patient. A l’heure actuelle, beaucoup de travaux numériques et expérimentaux sont effectués mais peu d’études ont permis de bien corréler les techniques d’imageries médicales pour l’aide au diagnostic. C’est dans ce contexte que se situent les travaux de ma thèse, réalisée en collaboration, à la fois avec le CHU de Dijon où ont été effectuées toutes les expérimentations à l’aide d’IRM, le laboratoire GMedTech, GMIT (Galway-Mayo Institute of Technology) en Irlande qui nous a fourni les répliques ainsi que leur savoir-faire dans le domaine cardio-vasculaire et le Laboratoire DRIVE situé à Nevers où ont été menées les mesures d’écoulement par PIV. Les travaux, menés sur des fantômes de diverses formes in vitro, ont pour finalité, d’une part, de construire une méthodologie métrologique pour aider les médecins à comprendre et à valider les mesures d’IRM à l’aide d’autres dispositifs de mesure, d’autre part, de permettre d’améliorer les méthodes de diagnostic des pathologies de type d’anévrisme de l’aorte abdominale. Le principe de ces travaux est donc de mettre en place une modélisation expérimentale in Vitro dans un cadre métrologique d’intercomparaison par divers moyens de mesure et de corréler leurs résultats au long d’un cycle reproduisant les conditions hémodynamiques de mesure, mais aussi de confronter ces résultats à de modélisations numériques. Pour prendre en compte le problème dans sa globalité, non seulement l’évolution de la déformation, représentant l’élasticité de l’aorte, a dû être étudiée mais aussi l’évolution du flux sollicitant la paroi (…). / The Abdominal Aorta Aneurysm (AAA) is a pathology that is defined by a localized and permanent dilation of the artery and which involves over 8.8% of the seniors. Currently, when a patient has a dilatation of the aorta leading to a surgery because of the rupture risk, the therapeutic decision is made depending on the diameter of the aneurysm. To determine this diameter, it is usually conducted an examination by medical imaging (ultrasound, CT, MRI...). However, it notes that the diagnosis can’t be satisfied with a single dimensional measurement face to induced risks: first of all, when the diameter exceed a certain growth, the risk of rupture can reach 50% but more than 5% of surgical procedures may cause the patient's death. Other metrics such as compliance of the artery can be used for the decision for surgery. Compliance corresponds to a precise definition by cardiologists: this is a quantity that characterizes the deformability, describing the ability of aorta to distend under the influence of blood pressure. From our point of view, this concept is insufficient because, generally, in the case of an aneurysm, rupture is highly localized because of the complexity of the shape. It is therefore necessary to extend its definition in a quantity not localized at a section or a specific location but to the whole wall. Diagnostics methods will be more reliable if they can determine localized compliance. From a mechanical standpoint, determining compliance is thus transformed into the measurement of localized parietal elasticity of aorta. The elasticity is not a directly measurable parameter. Therefore, the problem comes down to determining the local strain of the aortic wall in the hemodynamic condition. Solving this problem is complex. Indeed, the mechanical stresses are dependent on the flow of blood, the artery surrounding organs, the material properties of the artery and the geometry of the aneurysm which are specific to each patient. At present, many numerical and experimental works is done but few studies have well correlated medical imaging techniques for the diagnostic aid. It is in this context that are my thesis in collaboration both with the Dijon University Hospital where were performed all experiments using MRI and GMedTech laboratory GMIT (Galway- Mayo Institute of Technology) in Ireland who provided the replicas and their expertise in the cardiovascular area. This work, conducted on various form of phantoms in Vitro, are intended, first to build a metrological methodology to help doctors understand and validate MRI measurements using other devices measurement, on the other hand, to improve the methods of diagnosing the abdominal aortic aneurysm. The principle of this work is to develop experimental modeling in vitro in a metrology framework and correlate the results from different measurement techniques and numerical modeling throughout a cycle reproducing the hemodynamic conditions. To consider the problem as a whole, not only the evolution of deformation representing the elasticity of the aorta should be studied, but also the evolution of soliciting flow. Therefore, in this thesis, several devices such as stereovision, Particle image velocimetry (PIV), MRI kinetic sequence but also the flow 2D and 4D were employed. Various numerical models were established to not only correlate the results with those obtained experimentally, therefore, to improve the credibility of our study, but also to be part of the aid protocol to the diagnosis that we have proposed. In the end, all the results from different experimental and numerical models have led to propose a validated and feasible diagnosis protocol based on MRI sequences. The application of this protocol on a realistic AAA complex phantom showed its feasibility. We can therefore say that the feasibility of the proposed protocol is demonstrated and that based on MRI (…).

L’épidémiologie des anévrismes de l’aorte est un problème de santé publique majeur dans les pays industrialisés. Cette pathologie peut engendrer la mort du patient en cas de rupture de l’anévrisme. Actuellement les critères d’intervention chirurgicale sont basés sur la morphologie de l’anévrisme et il existe des difficultés à évaluer correctement le risque de rupture pour chaque patient. L’objectif de cette thèse était de développer une méthode d’identification des propriétés mécaniques de la paroi artérielle de manière personnalisée permettant d’affiner les critères d’intervention chirurgicale. Des essais de gonflement utilisant des mesures de champs et le développement d’une méthodologie d’analyse ont permis de quantifier la distribution des contraintes des anévrismes de manière expérimentale et de mettre en évidence l’apparition des affaiblissements ponctuels dans la paroi afin de prédire la localisation de la rupture de l’anévrisme. Ensuite, une méthode d’identification de propriétés mécaniques a été mise en place pour mettre en évidence l’hétérogénéité du tissu artériel et pour localiser les endroits à l’origine de la rupture du tissu. L’identification des lois de comportement à partir de données expérimentales issues de patients permettra d’améliorer les modèles numériques artériels utilisées aujourd’hui. De plus, la méthodologie créée pour l’analyse de la rupture d’anévrismes pendant cette thèse ouvre la porte à une étape qui vise à développer la caractérisation mécanique in-vivo par l’utilisation de l’imagerie médicale. L’objectif final sera d’évaluer le risque de rupture de l’anévrisme de chaque patient de manière non-invasive. / Epidemiology of aortic aneurysms is a major public health issue that affects a significant proportion of the population in industrialized countries and can cause the death of the patient in case of rupture of the aneurysm.Currently the only criteria for surgery are based on the morphology of the aneurysm, and there are problems to accurately assess the risk of rupture for each patient.The aim of this thesis was to develop a method to identify the mechanical properties of the arterial wall in a personalized way to refine the criteria for surgery.Inflation tests, full-field measurements and a methodology developed were used in order to quantify experimentally the stress distribution of aneurysms. It was possible to highlight the appearance of localized weakening in the wall which will let us predict the location of the rupture on the aneurysm. Then a method was developed to identify the mechanical properties of the aortic tissue. It was possible to highlight the heterogeneity of arterial tissue and locate the places where the rupture of the tissue may occur.The identification of the aneurysm’s mechanical properties from experimental data will improved arterial numerical models used today. In addition, the methodology developed for the analysis of the rupture of aneurysms during this thesis opens the door to a step that aims to develop the in vivo mechanical characterization by the use of medical imaging. The ultimate goal will be to assess the risk of rupture of the aneurysm of each patient in a noninvasive manner.

Atherosklerose ist eine häufige Erkrankung bei in Gefangenschaft gehaltenen Psittaciformes, deren ante mortem Diagnose sich jedoch schwer gestaltet. Während in der Säugetiermedizin die Anwendung mehrerer diagnostischer, insbesondere echokardiographischer Verfahren schon seit Jahren zur Routine zur Herz-Kreislauf-Diagnostik gehört, sind die Erfahrungen, besonders im Bereich der Echokardiographie beim Vogel, weiterhin limitiert. Referenzwerte gesunder Vögel fehlen häufig und machen die Auswertbarkeit ermittelter Daten schwierig. Ziel dieser Arbeit war es, verschiedene anamnestische und diagnostische Untersuchungen beim Kongograupapageien (Psittacus erithacus erithacus) und speziell die Pulsed-Wave-Doppler-Messung zur Diagnose einer Atherosklerose auszuwerten. Weiterhin wurde der Effekt einer Enalapril-Therapie im Hinblick auf die Blutflussgeschwindigkeit in der Aortenbasis bei Atherosklerose-verdächtigen Vögeln beurteilt. Hierzu wurden insgesamt 39 Kongograupapageien (Psittacus erithacus erithacus) untersucht. Sieben klinisch gesunde Tiere wurden der Kontrollgruppe zugeordnet. Beschriebene Risikofaktoren oder spezifische klinische Symptome wurden als Auswahlkriterium für insgesamt 32 Tiere der Patientengruppe berücksichtigt. Bei allen Tieren wurden, neben einer gründlichen Anamnese und einer klinischen Untersuchung, Röntgenbilder in zwei Ebenen angefertigt, Gesamtcholesterol- und Triglyzeridwerte im Blut bestimmt und es wurde eine echokardiographische Untersuchung unter Inhalationsnarkose durchgeführt. Hierbei wurde das Herz l im B-Mode, als auch mit Hilfe des Spektral-Dopplers untersucht und es wurden Messungen angefertigt. Lagen die gemessenen Werte in der Spektral-Doppler-Untersuchung über den gemessenen Referenzwerten, wurde die orale Behandlung mit Enalapril begonnen. Die statistische Auswertung der Messergebnisse erfolgte, nach Überprüfung auf Normalverteilung der metrischen Daten (Kolmogorov-Smirnov-Test), mit Hilfe des Levene-Signifikanztests und nachfolgend des T-Tests für unabhängige Stichproben, sowie der Korrelationsanalyse nach Pearson. Die statistische Bewertung der Scoringwerte erfolgte mittels Mann-Whitney-U-Test und Kendall-Tau-B-Test. Bei der Auswertung der medikamentellen Behandlung wurde auf eine statistische Auswertung aufgrund der Inhomogenität der individuellen Tiere verzichtet. Zwischen der Kontrollgruppe und der Patientengruppe waren signifikante Unterschiede hinsichtlich des Gesamtscorings (p < 0,001), der Blutflussgeschwindigkeit in der Aortenwurzel (p = 0,002), der Herzfrequenz (p = 0,038) und der Beurteilung der Aortendichte und des umgebenden Gewebes in der radiologischen Untersuchung (p = 0,018) erkennbar. Unabhängig von der Gruppenzugehörigkeit konnten signifikante Korrelationen zwischen der radiologischen Dichte im Bereich der Aorta und dem korrespondierenden Gesamtscoring (r = 0,415), dem Auftreten von klinischen Symptomen und der radiologische Dichte im Bereich der Aorta (r = 0,617), sowie Auffälligkeiten in der B-Mode-Echokardiographie und einer Erhöhung der Blutflussgeschwindigkeit in der Aortenwurzel (r = 0,422) festgestellt werden. Die Medikation mit Enalapril erwies sich in allen untersuchten Fällen generell als verhältnismäßig gut durchführbar und zielführend. Die vorliegende Arbeit konnte zeigen, dass die Spektraldoppler-Echokardiographie in Kombination mit anderen diagnostischen Verfahren zur Einschätzung des kardiovaskulären Status eines Vogels empfohlen werden kann und den Verdacht auf das Vorliegen einer Atherosklerose erhärten kann. Die speziellen Limitierungen dieser Studie beinhalten neben den individuellen Variationen zwischen den untersuchten Tieren und mangelnder Compliance der Tierhalter, außerdem das Fehlen von post mortem Beurteilungen der untersuchten Tiere.

L’aorte est une artère majeure et la rupture de l’aorte (RA) est la lésion la plus commune parmi les larges vaisseaux. Une RA est détectée dans 10 à 15% des cas mortels liés aux accidents de voiture et constitue la cause secondaire des morts consécutives aux chocs traumatiques associés à ces accidents. Les mécanismes variés de RA (éclatement soudain de l’aorte, la contrainte des structures osseuses, le « coup de bélier » et la combinaison de ces mécanismes) peuvent être considérés comme une combinaison de deux types de contributions : la distraction aortique et la pression aortique.L’objectif de ce travail de doctorat est d’étudier les mécanismes liés aux RAs dans les accidents de voitures en se focalisant sur les mécanismes associés à la pression intra-aortique. Le travail est organisé en quatre parties : 1) quantifier la réponse aortique sous des conditions de chargement physiologiques, 2) identifier la nécessité de considérer la pression intra-aortique dans les RA associés aux accidents, 3) développer un modèle d’éléments finis incluant la contribution des mécanisme de lésions et 4) et finalement étudier le mécanisme de RA avec le modèle nouvellement développé. / Blunt aortic rupture (BAR) is the second leading cause of death following blunt trauma in motor vehicle crash accidents (MVCAs). Aortic distraction was postulated to be a primary BAR mechanism, but intra-aortic pressure effect on BAR is controversial. Previous finite element (FE) simulations did not simultaneously study the BAR mechanisms of the two contribution sources. Therefore, the BAR mechanisms remain to be ascertained under the effects of physiological intra-aortic pressure and intra-thoracic interactions during MVCAs.Our objective is to investigate BAR mechanisms in MVCAs with a focus on intra-aortic pressure. The work is organized: 1) to quantify aortic responses under cardiac function, 2) to identify the necessity of considering intra-aortic pressure, 3) to develop a FE model including both injury contribution sources and 4) to investigate BAR mechanism during MVCA with the new model. The aortic responses under cardiac loadings should be considered for BAR. Intra-aortic pressure could induce a significant BAR risk. BAR in MVCA resulted from a combined mechanism with aortic stretch and intra-aortic pressure as the primary and secondary cause.

Background: Effects of cardiovascular (CV) risk factors on the diameter of the thoracic aorta have not been fully studied. This study examined the associations between CV risk factors and diameter of thoracic aorta. Materials and Methods: Study population comprised of 1273 asymptomatic adults aged ≥18 years from Central Appalachia region of the United States who participated in a coronary artery screening between January 2014 and December 2016. Descriptive statistics and multiple linear regression analyses were performed to examine associations between multiple CV risk factors and diameters of the thoracic aorta. Results: Mean (±SD) age of participants was 57.9±9.7 years; that of body mass index (BMI) was 29.4±5.9. The mean aortic sinus, ascending aorta, and descending aorta diameter were 34.1±4.4 mm, 33.8±4.4 mm, and 26.0±3.6 mm, respectively. Increasing age, being male, and having a higher BMI were associated with wider aortic sinus, ascending aorta, and descending aorta diameters. Hypertension (p < 0.05) and obesity (p < 0.0001) were significantly associated with wider diameter for all measured aortic diameters. Participants with diabetes had wider descending aorta compared to those without (26.6±3.9 mm vs. 25.9±3.5 mm, P = 0.012). Participants who had ever smoked a cigarette had significantly wider descending aorta diameter compared to never smokers (26.3±3.6 mm vs. 25.9±3.5 mm, p = 0.031). Conclusions: The study results suggest that decreasing BMI and management of CV risk factors such as hypertension and modifying behavioral risk factors such as smoking are likely to be emphasized in order to decrease the rate of aortic dilatation and subsequent aortic dissection, if aortic dilatation is detected during a CT scan.

Aorte est l'artère qui amortit et conduit le flux sanguin éjecté par le cœur en flux continu vers la périphérie. Avec l’âge, l'élasticité aortique diminue en association avec des altérations fonctionnelles et hémodynamiques de l’aorte et du cœur. Alors que l'hémodynamique artérielle a été largement étudiée par l'analyse des courbes de pression, les modifications de l’onde de débit aortique n’ont été que très peu explorées. L’imagerie IRM, couplée à une segmentation appropriée, permet une évaluation non-invasive et précise du débit sanguin aortique. Cette thèse combine ce débit mesuré en IRM avec les pressions tonométriques afin de proposer des indices quantitatives de rigidité artérielle. Ainsi, ce travail comprend: Une nouvelle approche, basée sur les ondelettes, pour estimer le temps de transit entre les ondes de flux provenant de deux sites aortiques. Ce dernier a permis de calculer la vitesse de l'onde de pouls dans la crosse, qui s’est avérée être un marqueur fort de la rigidité et de l’âge. Une analyse d'impédance aortique dans le domaine fréquentiel pour quantifier la charge pulsatile et les réflexions qui augmentent la charge exercée sur le cœur. Une quantification de la forme de l'onde de débit aortique, dont l’association avec les changements géométriques du cœur a été montrée. Une cartographie des pressions intra-aortiques absolues en utilisant les équations de Navier-Stokes. Ces nouveaux indices ont été testés sur 70 sujets sains et leur complémentarité en termes de caractérisation de l’âge et du couplage entre l'aorte et le cœur a été montrée. De futures études sur l'hypertension artérielle permettront de démontrer l'utilité clinique de nos indices. / Aorta is the artery which immediately accommodates the blood flow ejected from the heart. It buffers blood’s pulsatile momentum and conducts it smoothly towards periphery. With physiological aging, aortic elasticity diminishes significantly in association with aortic or cardiac functional and hemodynamic alterations. While aortic hemodynamics were widely studied through pressure curves analysis, proximal aorta flow patterns were only little investigated. Recent developments of cardiovascular magnetic resonance imaging (MRI) and image segmentation tools, enable an accurate non-invasive evaluation of proximal aortic blood flow. This thesis combined MRI with central pressure measurements by applanation tonometry to propose flow-indices of arterial stiffness. Indeed our work proposed: A new wavelet-based method, which enables temporal localization of signal frequencies to estimate transit-time between flow waves from two aortic sites, in order to derive aortic arch pulse wave velocity, which is a strong marker of stiffening and aging. An aortic impedance analysis in frequency domain to provide indices which reflect changes in aortic pulsatile load and wave reflection, which augments the load on the heart Quantitative flow-morphology indices which were shown to be associated with age-related changes in left heart geometry. Absolute intra-aortic pressure mapping using the Navier-Stokes equations. These new indices have been tested on 70 healthy volunteers and findings indicated their complementary nature in characterizing aging and aortic-heart coupling. Further investigations in the context of hypertension will prove the clinical usefulness of our indices.

This study investigated possible solutions to the current wartime problem of junctional hemorrhaging, or massive traumatic hemorrhaging in non-tourinquetable areas such as the neck, groin, or armpit. Junctional hemorrhaging has been identified as a major contributor to potentially survivable deaths seen on the battlefield today and therefore is a priority for the U.S. armed and coalition forces (Kragh et al., 2011a; Bozeman, 2011). Common tourniquets today are standard issue and carried by soldiers in the military, but are limited to distal extremity trauma. As the battlefield has changes however, trauma has transformed from commonly seen gunshot wounds to more extreme trauma such as dismounted complex blast injuries which typically includes loss of one or more appendages. These newly found situations render the traditional tourniquet ineffective. Thus, the development of a new tourniquet to control hemorrhaging from regions such as the neck, armpit, and groin has been deemed necessary. The development of a new tourniquet for hemorrhage control included market research, preliminary testing to determine design restraints, design ideation, finite element analysis, manufacturing a prototype, and prototype testing. Research and comparisons were done of the strengths and weaknesses of tourniquets already approved by the Food and Drug Administration (FDA). Next, design limitations were found using preliminary testing on a blood-flow replicate model developed by Tracey Cheung. The results from this testing provided a framework for designing a new tourniquet. A new approach to control junction hemorrhaging was then designed, built, and tested on the Cheung model. To verify the design, simplified models were analyzed using finite element analysis. The prototype was then tested and compared against the FDA approved tourniquets, listing the advantages and possible shortcomings.

No description available.

Dissertation (MD)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: Acute renal failure still is, with the exception of cardiac deaths, the most important pathological process associated with perioperative mortality in patients operated for abdominal aortic aneurysms. The intraoperative change in renal blood flow (RBF) and glomerular function have been investigated in human and animal models, particularly over the past 15 years. Despite large variation in study populations, measurement techniques and study designs in general, a significant body of evidence has developed which suggests infrarenal aortic clamp-induced renal ischemia to be the cause of postoperative acute renal failure when this complication does occur. It is rather surprizing then that, despite some recent studies which have reported on various pharmacological interventions to prevent intraoperative renal ischemia (with variable success), very little has apparently been done to unravel the pathogenesis and exact pathophysiology of this potentially lethal complication. Although a number of investigators suggest the possibility of hormonal involvement (particularly reninangiotensin, antidiuretic hormone (ADH) and catecholamines) in the process, the exact role of these mediators have not been explored (or reported) in a structured fashion. In an initial human study, renal hemodynamics and function were measured from the preoperative period, during the intraoperative phase and at least until 4 hours after aortic unclamping. To investigate the possibility of a temporal relationship between renal changes and fluctuations in hormonal concentrations, plasma concentrations of relevant hormones were determined at every sampling period where renal parameters were measured. The decrease in RBF and glomerular filtration rate (GFR) which we demonstrated to coincide with infrarenal aortic cross clamping, is consistent with results previously published. We demonstrated persistence of the impairment of these parameters as long as 4 hours into the postoperative phase; which has previously only been reported for the period until immediately after aortic unclamping with the abdomen still open. The persistence of a depressed GFR until the time of discharge of patients is cause for concern, particularly in patients with compromised renal function prior to surgery. Of the measured hormones with a potential influence on RBF and nephron function, renin was the only mediator where changes in plasma concentrations coincided with the depression of RBF and GFR after aortic cross clamping. The design of our study did not allow us to conclude whether the concomitant increase in angiotensin II was primarily responsible for the change in renal hemodynamics, or whether the raised renin (and angiotensin) levels were stimulated by the decrease in RBF induced by another mechanism. In another patient group, we demonstrated that the combination of mannitol and dopamine provided no protection against the deleterious effects of aortic cross clamping. In fact, the high urine volumes produced under the influence of these agents (which did not correlate with RBF at the corresponding periods), is likely to prompt a false sense of security. Given the lack of any objective benefit afforded by these agents, their use in these clinical circumstances should be discouraged. The animal studies were aimed at elucidation of the exact role of angiotensin in the pathogenesis and pathophysiology of the renal changes associated with infrarenal aortic clamping, as well as the interaction of angiotensin with other modulators for which an interactive relationship had been described previously under other experimental and/or clinical circumstances. The first study showed that, although renin (and thus angiotensin) concentrations were high after aortic unclamping, the hormone had no pathogenic or pathophysiological role of significance in the observed renal changes during this period (since blocking angiotensin II activation by the prevention of renin release, or by inhibiting the conversion enzyme, did not prevent a substantial decrease in RBF or GFR during that period). Preventing angiotensin II activation did, however, prevent renal changes during aortic clamping. This beneficial effect did not establish a primary role for angiotensin during that period, since the favourable influence could also (at least partially) be explained by prevention of the permissive influence of angiotensin on other vasoconstrictors and/or other vasodilatory influences of ACE inhibition and [1- blockade which are unrelated to angiotensin. This study did indicate that (at least partially) different mechanisms are responsible for the renal changes seen during aortic clamping, and after aortic unclamping. The second study explored the role of calcium in the renal pathophysiological changes during aortic clamping and after unclamping. The protective influence effected by the administration of a Ca2 + -blocker suggest the dependence of the renal vasoconstrictive and glomerular pathophysiological process( es) on the cellular influx of Ca2 + through voltage-gated channels. It unfortunately provides no definitive insight into the primary instigators of these processes. However, it does offer a clinically useful method of preventing these changes and protecting the kidney against ischemic injury during abdominal aortic surgery. The third component of the animal studies demonstrates the importance of the protective effect of renal prostaglandins during the specific experimental (and probably also the clinical) circumstances. Again, it does not provide definitive information on the mediators responsible for the renal changes, since the deleterious effects of numerous endogenous substances have previously been shown to be counterbalanced by intrarenal synthesis of prostaglandins under various experimental and clinical circumstances. The extent of the pathophysiological and ultrastructural changes which occurred under the influence of a NSAID does, however, suggest that these drugs should not be used under these clinical circumstances. The last component of the study provides evidence that angiotensin only plays a secondary/supplementary role in the renal pathophysiological process even during aortic clamping. This may explain the contradictory evidence regarding the potential beneficial effect of ACE inhibition (on renal hemodynamics and glomerular function) during abdominal aortic surgery (Licker et al. 1996, Colson et al. 1992a). Based on our studies, ACE inhibition can not be supported for this purpose. / AFRIKAANSE OPSOMMING: Akute nierversaking is met die uitsondering van kardiale sterftes, steeds die belangrikste patologiese proses wat geassosieer is met perioperatiewe mortaliteit in pasiënte wat opereer word vir abdominale aorta aneurismes. Die intraoperatiewe veranderinge in renale bloedvloei (NBV) en glomerulêre funksie is die afgelope 15 jaar ondersoek en gerapporteer in pasiënte- sowel as diere-modelle. Ten spyte van groot variasies in studie-populasies, meettegnieke en ontwerp van studies in die algemeen, dui 'n wesenlike hoeveelheid getuienis daarop dat infrarenale klemming van die aorta renale isgemie induseer, wat die oorsaak is van postoperatiewe akute nierversaking wanneer hierdie komplikasie voorkom. Dit is verbasend dat, ten spyte van sommige onlangse studies wat rapporteer oor 'n verskeidenheid farmakologiese ingrepe om intraoperatiewe renale isgemie te voorkom (met wisselende sukses), baie min oënskynlik gedoen is om die patogenese en die presiese patofisiologie van hierdie potensieel dodelike komplikasie te ontrafel. Hoewel verskeie outeurs die moontlikheid van hormonale betrokkenheid (veral renienangiotensien, antidiuretiese hormoon en katekolamiene) in hierdie proses suggereer, is die presiese rol van hierdie mediators nog nie op 'n gestruktureerde wyse ondersoek (of rapporteer) nie. In ons aanvanklike pasiënte-studie is renale hemodinamika en -funksie gemeet vanaf die preoperatiewe periode, gedurende die intra-operatiewe fase en tot minstens vier uur na ontklemming van die aorta. Serumkonsentrasies van relevante hormone is bepaal tydens elke metingsperiode waar renale parameters gemeet is, ten einde die moontlikheid van 'n temporale verwantskap tussen renale veranderinge en variasies in hormoonkonsentrasies te ondersoek. Die vermindering in NBV en glomerulêre filtrasiespoed (GFS) wat ons aangetoon het om saam te val met infrarenale aortaklemming, stem ooreen met resultate wat tevore deur ander navorsers publiseer is. Ons het aangetoon dat die inkorting van hierdie parameters voortduur tot minstens vier uur na aorta-ontklemming. Hierdie veranderinge is tevore slegs rapporteer vir periodes tot kort na aorta-ontklemming voor sluiting van die buikwond. Die feit dat die GFS steeds verlaag is met ontslag van hierdie pasiënte, skep rede tot kommer, veral in pasiënte wat alreeds ingekorte nierfunksie het voor die chirurgiese prosedure. Van die gemete hormone wat moontlik 'n invloed sou kon uitoefen op NBV eh nefronfunksie, was renien die enigste waarvan verandering in plasmakonsentrasies saamgeval het met die onderdrukking van NBV en GFS na aortaklemming. Die ontwerp van ons studie het ons nie toegelaat om 'n besliste uitspraak te maak of die geassosieerde verhoging in angiotensien II primêr verantwoordelik was vir die verandering in renale hemodinamika, of dat die verhoogde renien (en angiotensien) bloedvlakke moontlik sekondêr stimuleer is deur die verandering in NBV wat deur 'n ander meganisme induseer is. In 'n ander pasiëntegroep het ons aangetoon dat die kombinasie van mannitol en dopamien geen beskerming verleen het teen die nadelige effekte van aorta-klemming nie. Die groot volumes uriene wat uitgeskei is onder die invloed van hierdie middels (wat nie korreleer het met NBV tydens ooreenstemmende periodes nie), het inderwaarheid 'n ontoepaslike gerustheid uitgelok. Weens die ooglopende gebrek aan objektiewe voordeel wat verleen word deur hierdie middels, behoort hulle gebruik tydens hierdie kliniese omstandighede ontmoedig te word. Die doel van die diere studies was die identifisering van die presiese rol van angiotensien in die patogenese en patofisiologie van die renale veranderinge geassosieer met infrarenale aortaklemming, sowel as die interaksie van angiotensien met ander modulators waarvoor 'n interaktiewe verwantskap voorheen beskryf is onder eksperimentele en/of kliniese omstandighede. Die eerste studie het getoon dat alhoewel renien (en dus angiotensien) konsentrasies hoog was na aorta-ontklemming, die hormone geen betekenisvolle patogenetiese of patofisiologiese rol in die waargenome renale veranderinge gedurende hierdie periode het nie (aangesien blokkade van angiotensien aktivering deur voorkoming van renien vrystelling, of deur inhibisie van angiotensien omsettingsensiem (AOE), nie 'n daling in NBV of GFS kon voorkom nie). Voorkoming van angiotensien II aktivering het egter wel renale verandering voorkom gedurende aortaklemming. Dié voordelige effek het nie 'n primêre rol vir angiotensien gedurende die periode bevestig nie, aangesien die gunstige invloed ook (ten minste gedeeltelik) verduidelik kon word deur die voorkoming van die fassiliterende invloed van angiotensien op ander vasokonstriktore en/of ander vasodilator-invloede van die onderdrukking van AOE en ïs-blokkers (wat geen verband het met angiotensien of die blokkade daarvan nie). Die studie het aangetoon dat (ten minste gedeeltelik) verskillende meganismes verantwoordelik is vir renale veranderinge wat gesien is gedurende aortaklemming en na -ontklemming. Die tweede studie het die rol van kalsium in die renale patofisiologiese veranderinge gedurende aortaklemming en na ontklemming ondersoek. Die beskermende invloed wat deur die toediening van Ca2 + -blokkers bewerkstellig is, het bevestig dat die renale vasokonstriktoriese en glomerulêre patofisiologiese prosesse afhanklik is van sellulêre influks van kalsium deur spannings-afhanklike kannale. Dit het ongelukkig geen definitiewe insig verleen ten opsigte van die primêre inisieerders van die proses nie. Dit verskaf nogtans 'n bruikbare kliniese metode om daardie veranderinge te voorkom en die niere teen isgemiese besering gedurende abdominale aorta-chirurgie te beskerm. Die derde komponent van die diere-studies demonstreer die belangrikheid van die beskermende effek van renale prostaglandiene tydens die spesifieke eksperimentele (en waarskynlik ook die kliniese) omstandighede. Weereens gee dit nie definitiewe inligting oor die bemiddelaars wat verantwoordelik is vir die renale veranderinge nie, aangesien die skadelike effekte van verskeie endogene stowwe voorheen aangetoon is om beperk of voorkom te word deur die intrarenale vrystelling van prostaglandiene. Die omvang van die patofisiologiese en ultrastrukturele veranderinge wat ontstaan het onder die invloed van nie-steroïed anti-inflammatoriese middels (wat gebruik is om prostaglandien sintese te inhibeer), dui aan dat hierdie middels vermy moet word onder soortelyke kliniese omstandighede. Die laaste komponent van die studie verskaf 'n sterk aanduiding dat angiotensien slegs 'n sekondêre/aanvullende rol speel in die renale patofisiologiese proses, selfs gedurende aortaklemming. Dit mag die weersprekende getuienis oor die potensiële voordeel van AOE onderdrukking (op renale hemodinamika en glomerulêre funksie) gedurende abdominale aortachirurgie (Licker et al. 1996, Colson et al. 1992a) verklaar. Gebaseer op ons studies, kan AOE onderdrukking nie ondersteun word vir hierdie doel nie.

Apesar dos grandes avanços na medicina perioperatória, as operações vasculares ainda estão associadas a elevada morbi-mortalidade. A fisiopatologia dos eventos perioperatórios é complexa, envolvendo a instabilização de placas ateroscleróticas, o que não é contemplado nos algoritmos para estratificação de risco cardíaco perioperatório. Acreditamos que a identificação de características relacionadas à instabilização de placas incipientes, como alterações na reatividade vascular e maior atividade inflamatória, pode melhorar a acurácia da estimativa de risco e a análise do comportamento perioperatório destas características pode elucidar importantes mecanismos fisiopatológicos. Estudamos 100 pacientes com indicação de operação vascular e aferimos por meio de ultrassom-Doppler de artéria braquial, a hiperemia reativa (HR), marcador de função microvascular, e a dilatação mediada pelo fluxo (DMF), marcador de função endotelial, antes e após a operação. Analisamos também os níveis de proteina-C reativa ultra-sensível (PCR-us). A operação foi realizada em 96 pacientes e 27 deles apresentaram algum evento até o 30º dia pós-operatório: 4 óbitos cardíacos, 5 infartos agudos do miocárdio, 2 acidentes vasculares cerebrais isquêmicos, 2 elevações isoladas de troponina, 1 embolia de pulmão, 2 reoperações e 11 óbitos não cardíacos. Detectamos disfunção endotelial em 70% dos pacientes, mas não observamos nenhum padrão característico de comportamento perioperatório da DMF, ou associação significativa entre a mesma e os eventos. Observamos significativo aumento da PCR-us após a intervenção cirúrgica (0,5mg/dL x 3,01mg/dL, P=0,001), mas sem associação com eventos. Identificamos forte associação entre disfunção microvascular, representada pela menor velocidade de fluxo na artéria braquial durante a hiperemia reativa, e eventos: 81 cm/s + 20 x 95 cm/s + 28 ( P= 0,02). Concluímos que a identificação de disfunção microvascular no pré-operatório pode estratificar o risco de complicações perioperatórias e que embora não tenhamos observado piora da vasodilatação mediada pelo fluxo, não podemos afastar que haja piora da função endotelial no perioperatório. O aumento de PCR-us denota grande diátese inflamatória, que pode estar relacionada à disfunção endotelial. / Despite great advances in perioperative care, major vascular surgeries are still related to high morbidity and mortality. The pathophysiology of perioperative cardiac events is complex and comprehends atherosclerotic plaque instability, witch is not contemplated in the current algorithms for cardiac risk estimation. We hypothesized that the identification of characteristics related to predisposition for plaque instability, such as abnormalities in the vascular reactivity, is very promising and the characterization of this parameter`s behavior in the perioperative setting contributes to the better understanding of event\'s pathophysiology. We prospectively studied a cohort of 100 patients, candidates for elective major vascular surgery and assessed, by Doppler ultrasound in the brachial artery, reactive hyperemia(RH), a marker of microvascular function, and flow mediated dilation(FMD), a marker of endothelial function, before and after surgery. We also obtained C-reactive protein-high sensitive assay (CRP-hs) before and after surgery. Ninety six patients were submitted to the planned vascular surgery and 27 patients had an event up to the 30º postoperative day. We observed 4 cardiac deaths, 5 acute myocardial infarctions, 2 isolated troponin elevations, 2 ischemic strokes, 1 pulmonary embolism, 2 reoperations and 11 noncardiac deaths. Results: although there was no significant difference in the preoperative FMD between patients with and without events: 4.83% + 6.81 x 5.88% + 6.00 (p= .457), respectively, low RH response, measured as lower peak flow velocity in RH, was associated to events: 81 cm/s + 20 x 95 cm/s + 28 (p=0,02). There was no significant difference in the preoperative CRP-hs between groups (median: 0.51mg/dL (IQR 2.12) x 0.41mg/dL (IQR 0.59), p= .234). There was no significant difference between FMD before and after surgery but we detected an almost 6-fold increase in CRP-hs after surgery: 0.50mg/dL x 3.01mg/dL (p < .001), respectively. Our study demonstrated that microvascular dysfunction is closely related to perioperative events after major vascular surgery and is a better marker of perioperative risk than endothelial dysfunction, in specific conditions.