[Truncated abstract] Cardiac surgery involving cardiopulmonary bypass is a complex procedure that results in significant changes to blood coagulation, fibrinolytic biochemistry, platelet number and function, and the vasculature. These are due to pharmacological agents which are administered, haemodilution and contact of the blood with artificial surfaces. Consequently there are significant risks of thrombosis and haemorrhage associated with this procedure. The research presented in this thesis utilises in vitro, in vivo, and a novel ex vivo model to investigate the nature of the haemostatic defect induced by cardiopulmonary bypass. The components studied include the drugs heparin, protamine sulphate, and aprotinin, different types of bypass circuitry (including heparin bonded circuits) and procedures such as acute normovolaemic haemodilution. Patient variables, such as Factor V Leiden, are also studied. Each of these components is assessed for the effects on a number of laboratory measures of haemostasis including activated partial thromboplastin time, prothrombin time, activated protein C ratio, antithrombin concentration, heparin concentration, thrombin-antithrombin complex formation, prothrombin fragment 1+2 formation, markers of platelet surface activation and secretion, activated clotting time, haemoglobin concentration and coagulation factor assays.

Pulmonary dysfunction following cardiopulmonary bypass surgery is a widely explored complication and a multitude of factors have been implicated, including but not limited to: operative trauma; the cardiopulmonary bypass circuit; cardioplegia; the type of donor grafts utilised; anaesthesia and fluid administered. There is a paucity of information regarding the effect of cardioplegia on the lungs. No studies have previously investigated whether allowing cold-blood cardioplegic solution to enter the lung parenchyma, during the period of cardioplegia delivery, has an effect on the clinical outcome of lung function following cardiopulmonary bypass surgery. For this reason an original study was done to determine the effect of preventing cardioplegia from entering the lungs, by evacuating overflow of cardioplegia not drained via the atriocaval cannula, by using a pulmonary artery vent. A total of 403 patients admitted to undergo full cardiopulmonary bypass were screened and 142 patients who fitted the criteria for inclusion and provided informed consent took part in this prospective double blind randomised clinical trial. The control group underwent routine cardiopulmonary bypass grafting. The study group had the intervention of a pulmonary artery vent sutured in position at the time the heart was cannulated for bypass. During cardioplegia delivery the cardioplegia was removed via the atriocaval cannula in the control group (A) and via the atriocaval cannula and the pulmonary artery vent in the study group (B). Aside from this difference, the two groups were managed identically intra- and post-operatively. Outcomes which were compared included eight time measures of arterial blood gases; electrolytes and shunt fraction; bedside lung spirometry measures over five time periods; radiographic measures of atelectasis and effusion over three time points; as well as physiotherapy and hospitalisation requirements. Numerous other potentially extraneous variables were measured and compared in order to monitor homogeneity of the study samples. The consistency of the results within each group throughout the study provides strong evidence that the measurements taken were accurate. The use of standardised equipment and vigilant adherence to the protocol ensured no extraneous deviation. The internal validity of this study was therefore good and accurate. The findings of the study however brought into question a previously accepted belief that the pulmonary artery vent prevents the overflow of cardioplegia, not drained from the right atrium, from entering the lungs. There was no literature or previous studies to confirm or dispute this accepted ‘observation’ by cardiac surgeons that the cardioplegia does enter the lung parenchyma. To therefore validate the findings of the study a further four original studies were designed and initiated. The objective of these studies was to establish the efficacy of the pulmonary artery vent and to determine whether cardioplegia indeed circulates through the lung parenchyma or merely accumulates and ‘pools’. Technetium (Tc-99m), a radio labelled isotope was added to the cold blood cardioplegia solution prior to delivery in order to determine this. In the four sub-studies it was confirmed that the pulmonary artery vent is 90-100% effective in retrieving any cardioplegic solution not drained by the atriocaval cannulae, thus confirming the effectiveness of the pulmonary artery vent in preventing cold blood cardioplegic solution from entering the lungs. The findings of the main study confirmed that respiratory impairment after uncomplicated cardiopulmonary bypass, even in low risk patients, is relatively common, as within each group there was a significant change in outcome measures over time. Inter-group comparisons however showed these changes were not significant, with both groups deteriorating by the same degree post-operatively, therefore establishing that these changes were independent of the intervention of the pulmonary artery vent. In the control group, the cold blood cardioplegia solution that did not drain from the atriocaval cannula entered the lungs and circulated the lung parenchyma during cardiopulmonary bypass. The study group made certain that none, or very little, of the cold blood cardioplegia solution entered the lungs. The main findings of this study are therefore that pulmonary function and gas exchange, although markedly reduced following cardiac surgery, are not affected by placement and suctioning via a pulmonary artery vent during the time of cardioplegia delivery intraoperatively. Furthermore, these studies strongly suggest that cold blood cardioplegia solution is innocuous to the lungs / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, 2006.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

A Cirurgia de Revascularização do Miocárdio, realizada com o auxílio da Circulação Extracorpórea, está associada a alterações importantes na microcirculação e na produção e circulação de citocinas e marcadores inflamatórios. No presente estudo, foram avaliados 23 pacientes com indicação de Revascularização do Miocárdio, no dia do procedimento e 7 e 28 dias após a cirurgia. A microcirculação cutânea, enquanto reflexo da microcirculação coronariana, foi estudada através da hiperemia térmica e/ ou reativa pós oclusiva e da iontoforese de substâncias vasoativas por mecanismos dependentes e independentes do endotélio. A rigidez arterial foi aferida através da análise da onda de pulso digital. Foi avaliado ainda o impacto da doença e do procedimento cirúrgico sobre a produção e circulação sérica de citocinas e marcadores inflamatórios, tais como: PCR-HS, nitrito/ nitrato, IL-6, Il-7, IL-8, IL-10, IFN-γ, TNF-α e G-CSF. Foi observada uma tendência à redução da vasodilatação da microcirculação cutânea após a administração de doses acumulativas de acetilcolina (endotélio dependente) através da iontoforese de 7 e 28 dias após o procedimento cirúrgico. A hiperemia térmica foi mais pronunciada na avaliação basal do que aos 7 e 28 dias. A hiperemia reativa pós oclusiva não demonstrou alterações 7 dias após o procedimento. Aos 28 dias, houve um aumento da condutância microvascular cutânea. Quando avaliada a vasodilatação endotélio-independente (nitroprussiato de sódio), observamos aumento do fluxo microvascular cutâneo diretamente proporcional à carga/ dose aplicada, sem diferenças nos valores obtidos no basal e 7 e 28 dias após o procedimento. A rigidez arterial não apresentou alterações. A análise dos fatores inflamatórios e das citocinas demonstrou aumento marcante da IL-6 e da IL-8 após 7 dias do procedimento cirúrgico, com retorno parcial aos níveis basais da IL-6 e total da IL-8 após 28 dias. O IFN-γ, TNF-α e G-CSF apenas apresentaram níveis detectáveis na avaliação basal e IL-7 e IL-10 não demonstraram alterações significativas nos tempos avaliados. A PCR-HS demonstrou níveis mais elevados após 7 dias e retorno parcial aos níveis basais após 28 dias. O nitrito/ nitrato, após 7 dias, apresentou leve queda em sua concentração plasmática. Concluímos que a pequena diferença entre o valores obtidos entre o basal e após 7 dias do procedimento cirúrgico com a iontoforese de acetilcolina resulta em minimização do impacto endotelial e um valor constante deste dado após 28 dias, sugere recomposição fisiológica completa. Este resultado foi semelhante com a análise da hiperemia térmica e reativa pós oclusiva. As interleucinas IL-6 e IL-8, bem como a PCR-HS apresentaram comportamento correlacionável, refletindo a cinética inflamatória. A rigidez arterial não demonstrou alterações. / Myocardial Revascularization with cardiopulmonary bypass is associated with important modifications in the microcirculation and in the production and circulation of cytokines and inflammatory markers. In the present study 23 patients were evaluated on the day of the myocardial revascularization (baseline) and 7 and 28 days after the surgical procedure. The skin microcirculation that is in close relationship with coronary microcirculation was evaluated by iontophoresis of vasoactive substances, thermal hyperemia and post occlusive reactive hyperemia. The arterial stiffness was studied by digital pulse wave analysis. Cytokines and inflammatory markers such as C-reactive protein, nitrite/ nitrate, IL-6, Il-7, IL-8, IL-10, IFN-γ, TNF-α e G-CSF were also analyzed. A reduction in the skin microvascular vasodilatation was observed after iontophoresis of cumulative doses of acetylcholine (endothelium dependent) 7 and 28 days after the surgical procedure. Skin vasodilation after thermal hyperemia was more important before the surgery than 7 and 28 days after the procedure. The post occlusive reactive hyperemia did not cause vasodilation after 7 days of the surgery. After 28 days, the cutaneous microvascular conductance was higher than before. The iontophoresis of sodium nitroprusside (endothelium independent) showed increasing vasodilation according to the doses/ charge applied but there was no difference among the days of the study. The level of IL-6 and IL-8 increased after 7 days and the level of IL-8 returned to baseline after 28 days. IL-6 showed a reduction after 28 days but did not reach the baseline. IFN-γ, TNF-α e G-CSF were detected only on the day of the surgical procedure and the level of IL-7 and IL-10 was similar before, 7 days and 28 days after the surgery. Nitrite/ nitrate was reduced after 7 days of the surgical procedure. In conclusion we observed that the small difference between endothelium dependent vasodilation 7 days after the surgical procedure showed a reduction in the alterations caused by the extracorporeal circulation and the constant level of vasodilation after 28 days showed the complete recovery of the endothelium. This result was in accordance with thermal hyperemia and post occlusive reactive hyperemia. The kinetics ofIL-6, IL-8 C-reactive protein were similar. The arterial stiffness did not show any difference.

A circulação extracorpórea (CEC) é atualmente técnica amplamente utilizada na rotina da cirurgia cardíaca humana. Entretanto, na medicina veterinária, ainda não é utilizada rotineiramente devido a alta mortalidade que ocasiona. O presente experimento utilizou cinco cães machos, SRD, em condições satisfatórias para a realização de pesquisa médica. Esses animais foram submetidos a toracotomia intercostal direita convencional e realizadas as mensurações e coletas padrão pertinentes do experimento (M0). Após isso, os animais foram conectados a máquina de circulação extracorpórea, onde permaneceram por um período de duas horas (M1), sendo então desconectados da mesma, permanecendo por uma hora em processo de reperfusão pós CEC (M2) para após sofrer eutanásia. Foram avaliados os seguintes parâmetros: paO2 e pvO2 (oxigenação), paCO2 e pvCO2 (ventilação), pH e HCO3 (equilíbrio ácido-básico), Na, K e Ca ionizado (eletrólitos séricos), freqüência cardíaca, freqüência respiratória, temperatura retal, pressão arterial média, contagem de plaquetas, proteínas totais, glicose sérica, hematócrito, contagem de hemácias, avaliação anátomo-histopatológica do coração e pulmões. Foram observadas alterações significativas na oxigenação, ventilação, equilíbrio ácido-básico, eletrólito sérico potássio, freqüência cardíaca, temperatura retal, contagem de plaquetas, proteínas totais, glicose sérica, hematócrito, contagem de hemácias e no exame histológico do coração e pulmões. Fundamentado nos resultados verificados, concluiu-se que a circulação extracorpórea por duas horas com reperfusão durante 1 hora determina, em cães, alterações clínicas, modificações de parâmetros sanguíneos e induz processos patológicos no coração e pulmões / Actually cardiopulmonary bypass is frequently used in human cardiac surgery routine. However, in veterinary medicine, that does not happened because the high mortality produced. The present study was performed in five males mongrel dogs, in good health conditions for experimental purposes. These animals were submitted to a convencional right intercostal thoracotomy and it was collected the data and materials that concerns to the experiment (M0). Then the animals were connected to the cardiopulmonary bypass machine for a period of two hours (M1), disconnected of the machine and kept alive for a one hour period of reperfusion (M2) before the euthanasia. It was evaluated the paO2 e pvO2 (oxigenation), paCO2 e pvCO2 (ventilation), pH e HCO3 (acid-basic balance), Na, K e ionized Ca (serum electrolites), heart beats, respiratory movements, temperature, mean arterial pressure, platelets number, total protein dosage, serum glucose, hematocrit, red cells number, anatomic-histopathological evaluation of heart and lungs. It was observed significant alterations on the oxigenation, ventilation, acid-basic balance, potassium, heart beats, temperature, platelets number, total protein dosage, serum glucose, hematocrit, red cells number and at the anatomic-histhopathological exam of the heart and lungs. Evaluating the results, it was concluded that the cardiopulmonary bypass in dogs for two hours and a reperfusion period of one hour produced clinical alterations, blood parameters modifications and pathological process in the heart and lungs

O objetivo desta dissertação foi descrever em veterinária seqüência padrão de procedimentos que devem ser realizados nos períodos pré, trans e pós-circulação extracorpórea (CEC) para sua aplicação em cão, com base na literatura existente, e em observações levadas a efeito no Laboratório de Cirurgia Cardiotorácica, do Departamento de Cirurgia da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo. O referido trabalho concerne sobre a escolha do material, montagem e preparo da máquina ECOBEC ? Braile Biomédica - para circulação extracorpórea em cães, e descreve procedimentos básicos para entrada, condução, monitorização e saída de CEC, a fim de obter-se resultado técnico exeqüível no procedimento. Diante do exposto na literatura compulsada, baseado na metodologia e material proposto e com observações pessoais, é licito afirmar que esta é factível, desde que obedecidos os preceitos enumerados e descritos no presente trabalho para os períodos pré, trans e pós-circulação extracorpórea. / The purpose of this assay was to describe the standard basic procedures that should be followed before, during, and after cardiopulmonary bypass (CPB) in dogs, based on the existing literature and personal observations that took place in the Laboratory of Cardiothoracic Surgery, of the Surgical Department of the Faculdade de Medicina Veterinária e Zootecnia of the University of São Paulo. This assay reports how to choose the material, to prepare and to assemble the ECOBEC machine ? Braile Biomédica ? for cardiopulmonary bypass in dogs, and describes the basic procedures to start, conduct, follow up and finish it, in order to obtain a feasible technical results. Based on the literature, based on the methodology and material proposed and personal observations, it is reliable to state that this procedure can be accomplished since all paths described are followed before, during and after cardiopulmonary bypass.

A Cirurgia de Revascularização do Miocárdio, realizada com o auxílio da Circulação Extracorpórea, está associada a alterações importantes na microcirculação e na produção e circulação de citocinas e marcadores inflamatórios. No presente estudo, foram avaliados 23 pacientes com indicação de Revascularização do Miocárdio, no dia do procedimento e 7 e 28 dias após a cirurgia. A microcirculação cutânea, enquanto reflexo da microcirculação coronariana, foi estudada através da hiperemia térmica e/ ou reativa pós oclusiva e da iontoforese de substâncias vasoativas por mecanismos dependentes e independentes do endotélio. A rigidez arterial foi aferida através da análise da onda de pulso digital. Foi avaliado ainda o impacto da doença e do procedimento cirúrgico sobre a produção e circulação sérica de citocinas e marcadores inflamatórios, tais como: PCR-HS, nitrito/ nitrato, IL-6, Il-7, IL-8, IL-10, IFN-γ, TNF-α e G-CSF. Foi observada uma tendência à redução da vasodilatação da microcirculação cutânea após a administração de doses acumulativas de acetilcolina (endotélio dependente) através da iontoforese de 7 e 28 dias após o procedimento cirúrgico. A hiperemia térmica foi mais pronunciada na avaliação basal do que aos 7 e 28 dias. A hiperemia reativa pós oclusiva não demonstrou alterações 7 dias após o procedimento. Aos 28 dias, houve um aumento da condutância microvascular cutânea. Quando avaliada a vasodilatação endotélio-independente (nitroprussiato de sódio), observamos aumento do fluxo microvascular cutâneo diretamente proporcional à carga/ dose aplicada, sem diferenças nos valores obtidos no basal e 7 e 28 dias após o procedimento. A rigidez arterial não apresentou alterações. A análise dos fatores inflamatórios e das citocinas demonstrou aumento marcante da IL-6 e da IL-8 após 7 dias do procedimento cirúrgico, com retorno parcial aos níveis basais da IL-6 e total da IL-8 após 28 dias. O IFN-γ, TNF-α e G-CSF apenas apresentaram níveis detectáveis na avaliação basal e IL-7 e IL-10 não demonstraram alterações significativas nos tempos avaliados. A PCR-HS demonstrou níveis mais elevados após 7 dias e retorno parcial aos níveis basais após 28 dias. O nitrito/ nitrato, após 7 dias, apresentou leve queda em sua concentração plasmática. Concluímos que a pequena diferença entre o valores obtidos entre o basal e após 7 dias do procedimento cirúrgico com a iontoforese de acetilcolina resulta em minimização do impacto endotelial e um valor constante deste dado após 28 dias, sugere recomposição fisiológica completa. Este resultado foi semelhante com a análise da hiperemia térmica e reativa pós oclusiva. As interleucinas IL-6 e IL-8, bem como a PCR-HS apresentaram comportamento correlacionável, refletindo a cinética inflamatória. A rigidez arterial não demonstrou alterações. / Myocardial Revascularization with cardiopulmonary bypass is associated with important modifications in the microcirculation and in the production and circulation of cytokines and inflammatory markers. In the present study 23 patients were evaluated on the day of the myocardial revascularization (baseline) and 7 and 28 days after the surgical procedure. The skin microcirculation that is in close relationship with coronary microcirculation was evaluated by iontophoresis of vasoactive substances, thermal hyperemia and post occlusive reactive hyperemia. The arterial stiffness was studied by digital pulse wave analysis. Cytokines and inflammatory markers such as C-reactive protein, nitrite/ nitrate, IL-6, Il-7, IL-8, IL-10, IFN-γ, TNF-α e G-CSF were also analyzed. A reduction in the skin microvascular vasodilatation was observed after iontophoresis of cumulative doses of acetylcholine (endothelium dependent) 7 and 28 days after the surgical procedure. Skin vasodilation after thermal hyperemia was more important before the surgery than 7 and 28 days after the procedure. The post occlusive reactive hyperemia did not cause vasodilation after 7 days of the surgery. After 28 days, the cutaneous microvascular conductance was higher than before. The iontophoresis of sodium nitroprusside (endothelium independent) showed increasing vasodilation according to the doses/ charge applied but there was no difference among the days of the study. The level of IL-6 and IL-8 increased after 7 days and the level of IL-8 returned to baseline after 28 days. IL-6 showed a reduction after 28 days but did not reach the baseline. IFN-γ, TNF-α e G-CSF were detected only on the day of the surgical procedure and the level of IL-7 and IL-10 was similar before, 7 days and 28 days after the surgery. Nitrite/ nitrate was reduced after 7 days of the surgical procedure. In conclusion we observed that the small difference between endothelium dependent vasodilation 7 days after the surgical procedure showed a reduction in the alterations caused by the extracorporeal circulation and the constant level of vasodilation after 28 days showed the complete recovery of the endothelium. This result was in accordance with thermal hyperemia and post occlusive reactive hyperemia. The kinetics ofIL-6, IL-8 C-reactive protein were similar. The arterial stiffness did not show any difference.

No description available.

O estresse cirúrgico causa hiperglicemia, resultado de modificações endócrinas caracterizadas por diminuição da insulina e aumento simultâneo dos hormônios contra-reguladores. A circulação extracorpórea (CEC) provoca estresse intenso resultando também em hiperglicemia. A atenuação ou tratamento da hiperglicemia no estresse, no período perioperatório, de pacientes traumatizados, sépticos e críticos tem mostrado impacto favorável no prognóstico clínico. O objetivo da pesquisa foi: verificar se o controle intensivo da glicemia (80-120mg/dl) versus glicemia menor que 200mg/dl (convencional), ambos por meio de insulina venosa contínua, modificaria a morbiletalidade em cirurgias cardíacas com CEC. Realizou-se estudo randomizado, prospectivo, aberto em 98 pacientes. Medida da glicemia foi realizada durante e após a cirurgia, na unidade de terapia intensiva (máximo de 48 horas). Os pacientes foram comparáveis nos dados antropométricos e características clínicas, com exceção do peso e índice de massa corpórea nos diabéticos. Não houve diferença no tempo de intubação, permanência em UTI, insuficiência renal, disfunções neurológicas e mortalidade. Mostrou-se porém, no grupo de controle intensivo, tendência a menor tempo de hospitalização e infecção; e nos não diabéticos desse grupo, a quantidade de antifibrinolíticos utilizada foi menor, apesar da semelhança na quantidade de sangue transfundido / The stress response during surgery leads to hyperglicemia, resulting from endocrine alterations characterized by insulin decrease and simultaneous increase of counter-regulatory hormones. Cardiopulmonary bypass (CPB) causes intense stress response and hyperglicemia as well. Attenuating or treating hyperglicemia in stress response, in perioperative period, trauma, sepsis and critically ill patients has great impact in their clinical prognosis. This study had the objective of verifying if intensive glucose control (80-120mg/dl) versus less than 200mg/dl (conventional), both through continuous insulin infusion, will change hospital morbidity and mortality in patients undergoing open heart surgery with CPB. It was a prospective randomized, open trial in 98 patients. Glucose control was made during surgery and after in the intensive care unit (ICU) for 48 hours maximum. Patients from both glucose regimens resembled in all anthropometric clinical characteristics and in surgery data, except for the weight and body mass index in diabetic ones. There were no differences concerning time of ventilatory support, length of stay in ICU, acute renal failure, neurological disfunction and mortality. There were however, in the intensive regimen, tendency of lesser infection and length of stay in hospital; non-diabetic patients in this group used lesser quantity of antifibrinolytics, even though they received the same number of red-cell transfusions