Introdução. A insuficiência cardíaca (IC) é uma síndrome complexa que resulta em taxas elevadas de morbidade e mortalidade. Os pacientes em estágio avançado de IC podem ficar internados por um longo período para tratamento dessa síndrome. A restrição ao leito e a inatividade física prolongada geram complicações que resultam em piora na intolerância aos esforços, incluindo aqueles relacionados às atividades de vida diária. Por outro lado, existem evidências de que o tratamento com estimulação elétrica muscular de baixa frequência (EE) proporciona benefícios importantes para o paciente com IC. Neste estudo, nós testamos a hipótese de que o tratamento com EE melhora o controle neurovascular, a vasoconstrição periférica, a força muscular e a capacidade funcional em pacientes internados para tratamento da IC. Métodos. Trinta pacientes internados por IC descompensada, classe funcional IV da NYHA, fração de ejeção <= 30% foram consecutivamente randomizados em dois grupos: 1) EE funcional (n=15) e 2) controle, controle (n=15). A atividade nervosa simpática muscular (ANSM) foi avaliada diretamente no nervo fibular pela técnica de microneurografia, o fluxo sanguíneo muscular (FSM) do membro inferior e superior pela técnica de pletismografia de oclusão venosa, a frequência cardíaca e a pressão arterial pelo método indireto a cada batimento a batimento (Finometer), a força do músculo quadríceps femural por dinamometria, a capacidade funcional pelo teste de caminhada de seis minutos e a qualidade de vida pelo questionário Minnesota Living with Heart Failure. A EE funcional, iniciada após estabilização clínica, consistiu de estimulação dos membros inferiores, numa frequência de 10Hz, largura de pulso de 150ms, com ciclos de 20 segundos de estimulação e 20 segundos de repouso, durante 60 minutos, intensidade no limiar de desconforto do paciente até atingir um valor máximo de 70mA, por 10 dias consecutivos. O grupo controle seguiu o mesmo procedimento, exceto para a intensidade, que foi fixada em 20mA para não provocar contração muscular visível. Resultados. As características basais foram semelhantes entre os grupos estudados, apenas o grupo EE funcional tinha uma idade significativamente maior que o grupo controle. Após 10 dias de protocolo, a EE funcional reduziu a ANSM disparos/min e disparos/100 batimentos, aumentou o FSM e a condutância vascular na perna e no braço. Diferentemente, não houve alteração nestes parâmetros no grupo controle. Além disso, foi observado um aumento significativo da força do músculo quadríceps femural, na distância percorrida no teste de caminhada de seis minutos e na qualidade de vida em ambos os grupos. No entanto, a comparação entre os grupos mostrou que o aumento foi mais expressivo no grupo EE funcional em relação ao grupo controle. Conclusão. A EE muscular é uma intervenção segura que melhora o controle neurovascular, a vasoconstrição muscular, a capacidade funcional e a qualidade de vida em pacientes internados para tratamento da IC. Estes achados reforçam a importância da EE muscular em pacientes com IC na fase intra-hospitalar para compensação da síndrome / Introduction. Heart failure (HF) is a complex syndrome that results in elevated morbidity and mortality rate. Advanced HF patients may stay for a long period of time in the hospital for the treatment of HF. It is known that long-term bed rest and prolonged inactivity cause complications that result in worsening of exercise tolerance. On the other hand, there is evidence that treatment with low-frequency electrical stimulation (ES) provides important benefits for HF patients. Thus, we tested the hypothesis that treatment with ES improves neurovascular control, peripheral vasoconstriction, muscle strength and functional capacity in hospitalized advanced HF patients. Methods. Thirty hospitalized patients for treatment of decompensated HF, New York Heart Association class IV, left ventricular ejection fraction <= 30% were consecutively randomized into two groups: 1) Functional ES (n = 15) and 2) control (n = 15). Muscle sympathetic nerve activity (MSNA) was directly evaluated in the peroneal nerve by microneurography technique and lower and upper limb muscle blood flow by venous occlusion plethysmography. Heart rate and blood pressure were indirectly evaluated on beat-to-beat basis (Finometer). Quadriceps muscle strength was evaluated by dynamometer, functional capacity by six-minute walk test and quality of life by Minnesota Living with Heart Failure questionnaire. Functional ES, initiated after clinical stabilization, consisted of stimulation of lower limbs, at frequency of 10 Hz, pulse width of 150ms, with cycles of 20 seconds of stimulation and 20 seconds of rest for 60 minutes, according to the intensity threshold of patient discomfort until it reaches a maximum value of 70mA, 10 days. The control group followed the same procedure, except for the intensity, which was set at 20mA to not cause visible muscle contraction. Results. Baseline characteristics were similar between groups, except age that was higher in functional ES group. After 10 days of protocol, MSNA bursts/min and bursts/100 heart beats were significantly decreased in the patients submitted to ES. Functional ES increased lower and upper limb muscle blood flow and vascular conductance. In contrast, in the control group no changes in these parameters were found. Muscle strength, walk distance in six-minute walk test and quality of life were increased in both groups. However, the comparison between groups showed that these changes were greater in the functional ES group. Conclusion. ES is a safe intervention that significantly improves neurovascular control, vasoconstriction, functional capacity and quality of life in hospitalized advanced HF patients. These findings show the importance of the muscle ES in the treatment of hospitalized HF patients

Kentucky 31 tall fescue (KY31) infected with the common toxic endophyte strains of Epichloё coenophiala produces toxic alkaloids that improve plant vigor, but cause numerous adverse effects in grazing animals. Researchers developed a variety of KY31 containing an alternative strain of E. coenophiala, termed novel endophyte (NE). Adverse health effects in mares have not been evaluated. Experiments in this thesis tested the hypothesis that the NE pasture does not cause adverse effects typically associated with KY31. Specific aims were to: 1) compare forage ergovaline concentrations between KY31 vs NE pastures; 2) evaluate palmar artery diameters in mares grazing KY31, NE, or orchardgrass-bluegrass (OGBG) pastures; 3) determine mare serum prolactin, estradiol, and progesterone concentrations associated with ingesting each pasture type over time; and 4) measure foaling outcomes, including percentage of live foals, foal birth weights, and foal growth rates. In 2015, six nonpregnant mares grazed KY31, six pregnant mares grazed NE and six pregnant mares grazed OGBG pastures. In 2016, eighteen mares were used; six mares grazed each pasture type. Study results showed that ergovaline did not appear to be produced by NE. Novel endophyte pasture did not have negative effects on palmar artery diameter, reproductive hormones, or foaling outcomes.

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser. Även tryckt utgåva.

Objetivo: checar se poluentes do ar urbano de São Paulo induzem alterações sangüíneas e cardiopulmonares. MM: camundongos Balb/c foram expostos por 7, 14, 21, 30 e 45 dias em 3 câmaras: Limpa (controle), Intermediária (seletiva ao PM) e Suja (ar externo). Após exposição, os animais foram ventilados (FlexiVent) e coletados dados de mecânica pulmonar, sangue, coração e pulmão. Foram registrados PM, CO, SO2 e NO2 diários. Resultados: aos 21 e 45 dias coincidentes com picos de poluição houve aumento da resistência de via aérea (45d p=0,012), leucocitose (21d p < 0,001 e 45d p=0,039) e vasoconstricção pulmonar (21d p=0,034) nos animais da Câmara Suja, sem alteração de coronárias. Nenhum poluente excedeu limites de qualidade de ar / Objective: verify if air pollution of São Paulo city induces alterations in blood and cardiopulmonary systems. MM: Balb/c mice were exposed during 7, 14, 21, 30 and 45 days to 3 chambers: Clean (control), Intermediate (PM only) and Dirty (external air). After exposure, animals were ventilated (FlexiVent) and collected lung mechanics data and blood, heart and lung. PM, CO, SO2 e NO2 were measured daily. Results: on day 21 and 45, coincidently to peak of pollutions, there was proximal airway resistance increase (45d p=0.012), leukocytosis (21d p < 0.001 and 45d p=0.039) and vasoconstriction of peribronchiolar arterioles (21d p=0.034) in animals of Dirty Chamber with no alterations of coronaries. Neither pollutants exceeded the standard limits

Introdução. A insuficiência cardíaca (IC) é uma síndrome complexa que resulta em taxas elevadas de morbidade e mortalidade. Os pacientes em estágio avançado de IC podem ficar internados por um longo período para tratamento dessa síndrome. A restrição ao leito e a inatividade física prolongada geram complicações que resultam em piora na intolerância aos esforços, incluindo aqueles relacionados às atividades de vida diária. Por outro lado, existem evidências de que o tratamento com estimulação elétrica muscular de baixa frequência (EE) proporciona benefícios importantes para o paciente com IC. Neste estudo, nós testamos a hipótese de que o tratamento com EE melhora o controle neurovascular, a vasoconstrição periférica, a força muscular e a capacidade funcional em pacientes internados para tratamento da IC. Métodos. Trinta pacientes internados por IC descompensada, classe funcional IV da NYHA, fração de ejeção <= 30% foram consecutivamente randomizados em dois grupos: 1) EE funcional (n=15) e 2) controle, controle (n=15). A atividade nervosa simpática muscular (ANSM) foi avaliada diretamente no nervo fibular pela técnica de microneurografia, o fluxo sanguíneo muscular (FSM) do membro inferior e superior pela técnica de pletismografia de oclusão venosa, a frequência cardíaca e a pressão arterial pelo método indireto a cada batimento a batimento (Finometer), a força do músculo quadríceps femural por dinamometria, a capacidade funcional pelo teste de caminhada de seis minutos e a qualidade de vida pelo questionário Minnesota Living with Heart Failure. A EE funcional, iniciada após estabilização clínica, consistiu de estimulação dos membros inferiores, numa frequência de 10Hz, largura de pulso de 150ms, com ciclos de 20 segundos de estimulação e 20 segundos de repouso, durante 60 minutos, intensidade no limiar de desconforto do paciente até atingir um valor máximo de 70mA, por 10 dias consecutivos. O grupo controle seguiu o mesmo procedimento, exceto para a intensidade, que foi fixada em 20mA para não provocar contração muscular visível. Resultados. As características basais foram semelhantes entre os grupos estudados, apenas o grupo EE funcional tinha uma idade significativamente maior que o grupo controle. Após 10 dias de protocolo, a EE funcional reduziu a ANSM disparos/min e disparos/100 batimentos, aumentou o FSM e a condutância vascular na perna e no braço. Diferentemente, não houve alteração nestes parâmetros no grupo controle. Além disso, foi observado um aumento significativo da força do músculo quadríceps femural, na distância percorrida no teste de caminhada de seis minutos e na qualidade de vida em ambos os grupos. No entanto, a comparação entre os grupos mostrou que o aumento foi mais expressivo no grupo EE funcional em relação ao grupo controle. Conclusão. A EE muscular é uma intervenção segura que melhora o controle neurovascular, a vasoconstrição muscular, a capacidade funcional e a qualidade de vida em pacientes internados para tratamento da IC. Estes achados reforçam a importância da EE muscular em pacientes com IC na fase intra-hospitalar para compensação da síndrome / Introduction. Heart failure (HF) is a complex syndrome that results in elevated morbidity and mortality rate. Advanced HF patients may stay for a long period of time in the hospital for the treatment of HF. It is known that long-term bed rest and prolonged inactivity cause complications that result in worsening of exercise tolerance. On the other hand, there is evidence that treatment with low-frequency electrical stimulation (ES) provides important benefits for HF patients. Thus, we tested the hypothesis that treatment with ES improves neurovascular control, peripheral vasoconstriction, muscle strength and functional capacity in hospitalized advanced HF patients. Methods. Thirty hospitalized patients for treatment of decompensated HF, New York Heart Association class IV, left ventricular ejection fraction <= 30% were consecutively randomized into two groups: 1) Functional ES (n = 15) and 2) control (n = 15). Muscle sympathetic nerve activity (MSNA) was directly evaluated in the peroneal nerve by microneurography technique and lower and upper limb muscle blood flow by venous occlusion plethysmography. Heart rate and blood pressure were indirectly evaluated on beat-to-beat basis (Finometer). Quadriceps muscle strength was evaluated by dynamometer, functional capacity by six-minute walk test and quality of life by Minnesota Living with Heart Failure questionnaire. Functional ES, initiated after clinical stabilization, consisted of stimulation of lower limbs, at frequency of 10 Hz, pulse width of 150ms, with cycles of 20 seconds of stimulation and 20 seconds of rest for 60 minutes, according to the intensity threshold of patient discomfort until it reaches a maximum value of 70mA, 10 days. The control group followed the same procedure, except for the intensity, which was set at 20mA to not cause visible muscle contraction. Results. Baseline characteristics were similar between groups, except age that was higher in functional ES group. After 10 days of protocol, MSNA bursts/min and bursts/100 heart beats were significantly decreased in the patients submitted to ES. Functional ES increased lower and upper limb muscle blood flow and vascular conductance. In contrast, in the control group no changes in these parameters were found. Muscle strength, walk distance in six-minute walk test and quality of life were increased in both groups. However, the comparison between groups showed that these changes were greater in the functional ES group. Conclusion. ES is a safe intervention that significantly improves neurovascular control, vasoconstriction, functional capacity and quality of life in hospitalized advanced HF patients. These findings show the importance of the muscle ES in the treatment of hospitalized HF patients

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal. / Durant la grossesse normale, la pression artérielle et la réactivité vasculaire à plusieurs vasoconstricteurs diminuent. Ces changements hémodynamiques sont renversés durant la prééclampsie, soit une complication grave de la grossesse spécifique à l'humain. Des suppléments sodiques, 0.9% et 1.8% NaCI, administrés à des rates gestantes entraînent des symptômes caractéristiques de la prééclampsie. Ce nouveau modèle fut utilisé pour caractériser les mécanismes de réactivité vasculaire. Nous nous intéressions à l'activité des canaux potassique et calciques ainsi qu'aux récepteurs de l'endothéline. Des courbes concentration-réponse au tétraéthylammonium furent mesurées. Le tétraéthylammonium induit une contraction des anneaux aortiques seulement chez les rates non gestantes. Les suppléments sadiques n'ont pas induit de réponse au tétraéthylammonium sur les tissus de rates gestantes. Les effets de différents modulateurs de canaux potassiques (cromakalime et NS-1619) et calciques (nifédipine) sur les réponses myotropes à la phényléphrine, au chlorure de potassium et à la vasopressine furent mesurés. Les résultats obtenus suggèrent que chez les rates gestantes recevant des suppléments sodiques, l'activité des canaux KATP diminue tandis que celles des canaux Kca et des canaux calciques dépendants du voltage augmentent. Des courbes concentration-réponse à l'endothéline-1 furent mesurées en absence et en présence de BQ123. La sarafotoxine fut aussi testée. Les résultats obtenus suggèrent que les suppléments sadiques modulent la sensibilité des EÎA de façon différente chez les rates non gestantes et gestantes et que les ETe sont absents des muscles lisses de l'aorte thoracique. Les changements induits par les suppléments sadiques pourraient être caractéristiques de la prééclampsie.

Einleitung: Das ARDS (acute respiratory distress syndrome) stellt mit einer schweren Hypoxämie aufgrund eines hohen pulmonalen Recht-Linksshunts, mit einer pulmonalen Hypertonie und einer diffusen inflammatorischen Reaktion der gesamten Lunge trotz einiger etablierter Therapieansätze ein häufig letal endendes Krankheitsbild dar. Neben zahlreichen neuen klinisch-experimentellen Therapieansätzen erlangt die i.v.-Aplikation von Almitrindimesilat größere Beachtung. Zuerst verabreicht bei chronisch obstruktiven Atemwegserkrankungen erkannte man bald, daß neben der ventilationssteigernden Wirkung auch Effekte an der pulmonalen Gefäßstrombahn im Sinne einer Optimierung des Ventilations-Perfusions-Verhältnisses für die zu beobachtende Verbesserung der pulmonalen Oxygenation verantwortlich sind. Eine Potentierung der Hypoxischen Pulmonalen Vasokonstriktion (HPV) wird dafür verantwortlich gemacht. Kontrovers diskutierte Dosierungen in Tierversuchen und vereinzelten Anwendungen am Menschen legten nahe, daß systemische Dosis-Wirkungsanalysen erfolgen mußten. Desweiteren sollte untersucht werden ob die im Rahmen des ARDS zu beobachtende Pulmonalarterielle Hypertonie durch das Medikament zunimmt. Methoden: Mit Hilfe eines durch repetitive saline bronchoalveoläre Lavage induzierten ARDS-Modells am Schwein wurden an 14 Schweinen in Narkose prospektiv randomisiert entweder sechs ansteigende Dosen (0,5, 1, 2, 4, 8, und 16 (g/kgKG/min) Almitrindimesilat oder dessen Solvens Apfelsäure appliziert. Während des Versuches wurde volumenkontrolliert beatmet (FiO2 1,0 , PEEP 5 cm H2O). Nach je 30 minütiger Infusion der entsprechenden Dosierungen wurde Parameter des Gasaustausches und der pulmonalen sowie der systemischen Hämodynamik erhoben. Innerhalb der Gruppen wurde mittels des einfachen ANOVA-Test mit Bonferonikorrekturfaktor, zwischen den Gruppen mit dem Mann-Whitney-Test auf signifikante Unterschiede hin untersucht. Signifikanz der Unterschiede wurde bei einer Irrtumswahrscheinlichkeit p ( 0,05 angenommen. Ergebnisse: Niedrige Dosierungen, 0,5 - 2 (g/kgKG/min, reduzieren die venöse Beimischung und führen zu einem statistisch signifikanten Anstieg des Sauerstoffpartialdruckes mit einem Optimum für diesen günstigen Einfluß bei einer Infusionsrate von 1 µg/kgKG/ min. Hohe Dosierungen hingegen erhöhen die venöse Beimischung und senken den Sauerstoffpartialdruck und führen damit zu einer erheblichen Verschlechterung des Krankheitsbildes im Vergleich zu niedrigen Dosen und der Ausgangssituation bzw. dem nichttherapierten Tieren. Der Pulmonalarterielle Mitteldruck nahm nach Almitrindimesilatgabe geringfügig zu. Mit zunehmender Dosierung erreichte der MPAP höhere Werte als zum Zeitpunkt des stabilen Lungenschadens, jedoch waren keine dieser Steigerungen statistisch signifikant. Diskussion: Almitrindimesilat zeigte einen dosisabhängigen Einfluß auf den pulmonalen Gasaustausch. Dieser wirkt sich in niedrigen Dosierungen positiv auf die Hypoxämie aus. Der Pulmonalarterielle Druck bleibt konstant. Als Mechanismus der positiven Auswirkung liegt eine Potenzierung der HPV für niedrige Dosierungen nahe. / Objectives: The ARDS (acute respiratory distress syndrome) is characterized by a diffuse inflammatory response, a pulmonary hypertension and a severe hypoxemia mainly because of ventilation-perfusion-mismatching. Despite of some new therapeutical strageties the mortality remains high. Almitrine bismesylate was first described to improve arterial oxygenation in COPD- patients primary by increasing alveolar ventilation due to a stimulating effect on peripheral chemoreceptors. Furthermore several experimental studies have confirmed that almitrine improves PaO2 possibly because of reducing the ventilation- perfusion-mismatching by enhancing the hypoxic pulmonary vasoconstriction (HPV). Controversal results have been reported concernig the doses of intravenous Almitrine to be beneficial. Furthermore it remains unclear to what extend the pulmonary hypertension is augmented by a drug which is inhancing or restroring the HPV. Therefore we determined a dose-response-curve of almitrine in a animal model of ARDS. Methods: After induction of anaesthesia the ARDS-Modell was induced by repeated saline wash-0,5-2 ?g/kgKG/minout of surfactant. 14 swine received almitrine or the solvent in a prospective randomized manner. During the experiment the volume controlled mode of mechanical ventilation remained unchanged (FiO2 1,0 , PEEP 5 cm H2O). After the increasing doses of 0,5, 1, 2, 4, 8 and 16 ?g/kgKG/min each for 30 min we investigated the effects of i.v. almitrine on the pulmonary gasexchange and the pulomanry and systemic hemodynamics. Statistics were carried out by Two way Analysis of Variance p

Ce projet illustre cinq études, mettant l'emphase sur le développement d'une nouvelle approche diagnostique cardiovasculaire afin d'évaluer le niveau d’oxygène contenu dans le myocarde ainsi que sa fonction microvasculaire. En combinant une séquence de résonance magnétique cardiovasculaire (RMC) pouvant détecter le niveau d’oxygène (OS), des manœuvres respiratoires ainsi que des analyses de gaz artériels peuvent être utilisés comme procédure non invasive destinée à induire une réponse vasoactive afin d’évaluer la réserve d'oxygénation, une mesure clé de la fonction vasculaire. Le nombre de tests diagnostiques cardiaques prescrits ainsi que les interventions, sont en pleine expansion. L'imagerie et tests non invasifs sont souvent effectués avant l’utilisation de procédures invasives. L'imagerie cardiaque permet d’évaluer la présence ou absence de sténoses coronaires, un important facteur économique dans notre système de soins de santé. Les techniques d'imagerie non invasives fournissent de l’information précise afin d’identifier la présence et l’emplacement du déficit de perfusion chez les patients présentant des symptômes d'ischémie myocardique. Néanmoins, plusieurs techniques actuelles requièrent la nécessité de radiation, d’agents de contraste ou traceurs, sans oublier des protocoles de stress pharmacologiques ou physiques. L’imagerie RMC peut identifier une sténose coronaire significative sans radiation. De nouvelles tendances d’utilisation de RMC visent à développer des techniques diagnostiques qui ne requièrent aucun facteur de stress pharmacologiques ou d’agents de contraste. L'objectif principal de ce projet était de développer et tester une nouvelle technique diagnostique afin d’évaluer la fonction vasculaire coronarienne en utilisant l' OS-RMC, en combinaison avec des manœuvres respiratoires comme stimulus vasoactif. Ensuite, les objectifs, secondaires étaient d’utilisés l’OS-RMC pour évaluer l'oxygénation du myocarde et la réponse coronaire en présence de gaz artériels altérés. Suite aux manœuvres respiratoires la réponse vasculaire a été validée chez un modèle animal pour ensuite être utilisé chez deux volontaires sains et finalement dans une population de patients atteints de maladies cardiovasculaires. Chez le modèle animal, les manœuvres respiratoires ont pu induire un changement significatif, mesuré intrusivement par débit sanguin coronaire. Il a été démontré qu’en présence d'une sténose coronarienne hémodynamiquement significative, l’OS-RMC pouvait détecter un déficit en oxygène du myocarde. Chez l’homme sain, l'application de cette technique en comparaison avec l'adénosine (l’agent standard) pour induire une vasodilatation coronarienne et les manœuvres respiratoires ont pu induire une réponse plus significative en oxygénation dans un myocarde sain. Finalement, nous avons utilisé les manœuvres respiratoires parmi un groupe de patients atteint de maladies coronariennes. Leurs myocardes étant altérées par une sténose coronaire, en conséquence modifiant ainsi leur réponse en oxygénation. Par la suite nous avons évalué les effets des gaz artériels sanguins sur l'oxygénation du myocarde. Ils démontrent que la réponse coronarienne est atténuée au cours de l’hyperoxie, suite à un stimuli d’apnée. Ce phénomène provoque une réduction globale du débit sanguin coronaire et un déficit d'oxygénation dans le modèle animal ayant une sténose lorsqu’un supplément en oxygène est donné. En conclusion, ce travail a permis d'améliorer notre compréhension des nouvelles techniques diagnostiques en imagerie cardiovasculaire. Par ailleurs, nous avons démontré que la combinaison de manœuvres respiratoires et l’imagerie OS-RMC peut fournir une méthode non-invasive et rentable pour évaluer la fonction vasculaire coronarienne régionale et globale. / This project encompasses five studies, which focus on developing a new cardiovascular diagnostic approach for assessing myocardial oxygenation and microvascular function. In combination with oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging, breathing maneuvers and altered arterial blood gases can be used as a non-invasive method for inducing a vasoactive response to test the oxygenation reserve, a key measurement in vascular function. The number of prescribed cardiac diagnostic tests and interventions is rapidly growing. In particular, imaging and other non-invasive tests are frequently performed prior to invasive procedures. One of the most common uses of cardiac imaging is for the diagnosis of significant coronary artery stenosis, a critical cost factor in today’s health care system. Non-invasive imaging techniques provide the most reliable information for the presence and location of perfusion or oxygenation deficits in patients with symptoms suggestive of myocardial ischemia, yet many current techniques suffer from the need for radiation, contrast agents or tracers, and pharmacological or physical stress protocols. CMR imaging can identify significant coronary artery stenosis without radiation and new trends in CMR research aim to develop diagnostic techniques that do not require any pharmacological stressors or contrast agents. For this project, the primary aim was to develop and test a new diagnostic technique to assess coronary vascular function using OS-CMR in combination with breathing maneuvers as the vasoactive stimulus. Secondary aims then used OS-CMR to assess myocardial oxygenation and the coronary response in the presence of altered arterial blood gases. An animal model was used to validate the vascular response to breathing maneuvers before translating the technique to human subjects into both healthy volunteers, and a patient population with cardiac disease. In the animal models, breathing maneuvers could induce a significant change in invasively measured coronary blood flow and it was demonstrated that in the presence of a haemodynamically significant coronary stenosis, OS-CMR could detect a myocardial oxygen deficit. This technique was then applied in a human model, with healthy participants. In a direct comparison to the infusion of the coronary vasodilator adenosine, which is considered a standard agent for inducing vasodilation in cardiac imaging, breathing maneuvers induced a stronger response in oxygenation of healthy myocardium. The final study then implemented the breathing maneuvers in a patient population with coronary artery disease; in which myocardium compromised by a coronary stenosis had a compromised oxygenation response. Furthermore, the observed effects of arterial blood gases on myocardial oxygenation were assessed. This demonstrated that the coronary response to breath-hold stimuli is attenuated during hyperoxia, and this causes an overall reduction in coronary blood flow, and consequently an oxygenation deficit in a coronary stenosis animal model when supplemental oxygen is provided. In conclusion, this work has improved our understanding of potential new diagnostic techniques for cardiovascular imaging. In particular, it demonstrated that combining breathing maneuvers with oxygenation-sensitive CMR can provide a non-invasive and cost-effective method for assessing global and regional coronary vascular function.

Os mecanismos envolvidos na associação entre poluição do ar e aumento da mortalidade cardiovascular não estão ao todo esclarecidos. O objetivo deste estudo foi testar os efeitos agudos do PM2.5 da cidade de São Paulo sobre a freqüência cardíaca (FC), variabilidade da freqüência cardíaca (VFC), inflamação sistêmica e vasoconstrição de arteríolas de ratos Wistar saudáveis. O PM2.5 foi coletado em filtros de fibra de vidro utilizando um amostrador de grandes volumes. Para o ECG foram utilizados 47 ratos que foram submetidos a instilação traqueal de: salina, filtro branco, 50 ?g e 100 ?g de PM2.5. A freqüência cardíaca (FC) e o desvio-padrão dos intervalos NN (SDNN) foram avaliados na fase pré, 30 e 60 minutos após a instilação. Outro grupo de 38 ratos foram submetidos a instilação traqueal de: filtro branco, 100 ?g e 500 ?g de PM2.5 para análises hematológicas e histopatológicas. Estes animais foram sacrificados 24 horas após a instilação traqueal para a coleta de sangue e amostras de pulmão e coração para a morfometria e análise da razão peso seco/úmido. A FC diminuiu significativamente (p<0.001) com o tempo, mas não houve efeito de tratamento ou interação entre tempo e tratamento. O SDNN diminuiu 60 minutos após a instilação nos grupos de 50 ?g e 100 ?g de PM2.5 (p=0.025). O número de reticulócitos aumentou significativamente em ambas as doses de PM2.5 (p<0.05), enquanto que o hematócrito aumentou somente no grupo de 500 ?g (p<0.05). Segmentados, neutrófilos e fibrinogênio diminuíram significativamente, enquanto que os linfócitos aumentaram com 100 ?g de PM2.5 (p<0.05). Houve uma diminuição dose-dependente da razão luz/parede (L/P) das arteríolas pulmonares intra-acinares em ambos grupos de PM (p<0.001). A razão L/P das arteríolas peri-bronquiolares diminuiu no grupo que recebeu 500 ?g de PM2.5 (p<0.001). Houve um aumento significativo da razão peso seco/úmido no coração para o grupo que recebeu 500 ?g (p<0.001). Concluindo, as partículas finas da cidade de São Paulo induzem a uma redução do SDNN e promovem alterações histológicas pulmonares e cardíacas, resultando em significante vasoconstrição. A medula óssea também participou na resposta aguda promovida pelas partículas que alcançam os pulmões / The mechanisms involved in the association between air pollution and increased cardiovascular mortality are not fully understood. The objective of this study was to test the acute effects of Sao Paulo PM2.5 on heart rate, heart rate variability, systemic inflammation and vasoconstriction of arterioles of healthy Wistar rats. PM2.5 was collected in glass fiber filters using a high volume sampler. Forty-seven rats were submitted to tracheal instillation with: saline, blank filter, 50 ?g and 100 ?g of PM2.5 to ECG analysis. Heart rate (HR) and standard deviation of the intervals between normal beats (SDNN) were assessed immediately before, 30 and 60 minutes after instillation. Another thirty-eight rats were submitted to tracheal instillation with: blank filter, 100 ?g and 500 ?g of PM2.5 to hematological and histopathological analysis. These animals were sacrificed 24 hours after instillation when blood, heart and lung samples were collected for morphological and wet-to-dry weight ratio analysis. HR decreased significantly (p< 0.001) with time, but no significant effect of treatment or interaction between time and treatment was observed. SDNN decreased 60 minutes after instillation in groups PM2.5 50 ?g and 100 ?g (p=0.025). Reticulocytes significantly increased at both PM2.5 doses (p<0.05) while hematocrit levels increased in the 500 ?g group (p<0.05). Segmented, neutrophils and fibrinogen levels significantly decreased, while lymphocytes increaseded with 100 ?g of PM2.5 (p<0.05). A significant dose-dependent decrease of intra-acinar pulmonary arterioles Lumen/Wall ratio (L/W) was observed in PM groups (p<0.001). Peribronchiolar arterioles L/W showed a significant decrease in the 500?g group (p<0.001). A significant increase in heart wet-to-dry weight ratio was observed in the 500 ?g group (p<0.001). In conclusion, fine particles in the city of Sao Paulo induces a reduction of SDNN and promote pulmonary and cardiac histological alterations, resulting in significant vasoconstriction. In addition, we observed that the bone marrow also participated in the acute response to particles reaching the lungs

Laparoscopic operations are a common and popular way for abdominal procedures. They are usually performed by insufflation of carbon dioxide (CO2) into the abdominal cavity. However, insufflation of CO2 may interfere with cardiac and circulatory as well as respiratory functions. The CO2-pneumoperitoneum (PP) may cause hypercarbia and acidosis. The direct effects of CO2 and acidosis lead to decreased cardiac contractility, sensitization of the myocardium to arrhythmogenic effects of catecholamines and systemic vasodilatation. There may even be long-lasting post-operative effects on breathing control. The pneumoperitoneum may also cause several respiratory changes, e.g. decreased functional residual capacity (FRC) and vital capacity (VC), formation of atelectasis, reduced respiratory compliance and increased airway pressure. Still, arterial oxygenation is mostly maintained or even improved during PP. In view of the apparently contradictory results in respiratory mechanics and gas exchange, the present studies were performed to evaluate respiratory changes on gas exchange and ventilation-perfusion distributions during PP in a porcine model. It was demonstrated that atelectasis during anaesthesia and PP may be estimated by an increased arterial to endtidal PCO2-gradient (study I). Perfusion was redistributed away from dorsal, collapsed lung regions when PP was established. This resulted in a better ventilation-perfusion match (study II). Increasing abdominal pressure shifted blood flow more and more away from collapsed lung tissue, decreased pulmonary shunt and improved oxygenation from 8 to 16 mmHg PP, despite an increase of atelectasis formation (study III). CO2-PP enhanced the shift of blood flow towards better ventilated parts of the lung compared to Air-PP. Moreover, sodium natriumprusside worsened the ventilation-perfusion match even more and blunted the effects previously seen with carbon dioxide. CO2 should therefore be the mediator of enhancing HPV during PP. In conclusion, pneumoperitoneum with CO2 causes atelectasis with elimination of ventilation in the dependent lung regions. However, an efficient shift of blood flow away from collapsed, non-ventilated regions results in a better ventilation-perfusion matching and better oxygenation of blood than without PP. A prerequisite for the beneficial effect is the use of carbon dioxide for the abdominal inflation, since it enhances HPV.