Avaliamos os efeitos da estimulação atrial temporária na prevenção da fibrilação atrial no pós-operatório de revascularização do miocárdio com circulação extracorpórea e identificamos os fatores de risco para o aparecimento dessa arritmia. Estudamos 240 pacientes que ao término da cirurgia de revascularização miocárdica submeteram-se ao implante de eletrodos epicárdicos na parede lateral do átrio direito e no teto do átrio esquerdo e foram randomizados em grupo não estimulado, grupo com estímulo atrial direito e grupo com estímulo simultâneo nos átrios direito e esquerdo. Concluímos que a estimulação atrial temporária reduziu a incidência de fibrilação atrial pós-operatória e que a idade avançada e a não estimulação atrial foram fatores preditivos independentes para a ocorrência da arritmia / We studied the effects of temporary atrial pacing to prevent the atrial fibrillation after coronary artery bypass graft surgery and the risk factors to occurrence of this arrhytmia. We followed-up 240 patients after coronary artery bypass graft surgery who suffered temporary pacing atrial implantation at the end of operation. The patients were randomized into three groups according pacing stimulation into right atrial pacing, biatrial pacing and no stimulated patients. We concluded that the temporary atrial pacing reduced the incidence of postoperative atrial fibrillation. In addition older age was also a predictive factor of occurrence of atrial fibrillation

Made available in DSpace on 2016-01-26T12:51:32Z (GMT). No. of bitstreams: 1 renatageronfinoti_dissert.pdf: 2240331 bytes, checksum: e80f129b0db02c473d3a9c4f5162e004 (MD5) Previous issue date: 2011-11-29 / To analyze the security and efficacy of a new membrane oxygenator, the so-called OXM 1500. Methods: From May 2005 to September 2006, six sheep of Santa Inês breed (5 male and 1 female, respectively) were studied. The average body weight was 14.1 (±5) kg, body surface 0.6 (±0.2) m2 and a mean age 3.8 (±1.5) months. All of them were submitted to extracorporeal circulation (CEC) with evaluation at 10, 30, 60, 120, 180 and 240 minutes. The following values were obtained: values of oxygen transference (TTO2) and carbon dioxide transference (TTCO2), haemoglobin (HBS) and free haemoglobin (HBL), the score of platelets and of leucocytes, and heat transference rate. Results: TTO2 and TTCO2 were adequate. Lesion of the majority formed blood elements was insignificant; there no modifications in HBS, HBL levels; platelets and leucocytes decreased over time. Heat exchange was effective (p ≤ 0.05). Conclusions: The membrane OXM 1500 infant oxygenator, tested in sheep, showed adequate oxygenation capacity, CO2 removal capacity, and small alteration of haemoglobin and platelets without significant decrease of leucocytes, as expected. Heat exchanger connected to the oxygenator was efficient in temperature changes. / Analisar a segurança e a eficácia de um novo oxigenador de membrana denominado OXM -1500. Métodos: No período de maio de 2005 a setembro de 2006, foram estudados seis ovinos da raça Santa Inês, sendo cinco machos e uma fêmea, com peso corpóreo médio de 14,1 (±5) kg, superfície corpórea de 0,6 (±0,2) m2 e idade média de 3,8 (±1,5) meses. Todos foram submetidos à circulação extracorpórea (CEC) com avaliação nos tempos 10, 30, 60, 120, 180 e 240 minutos, obtendo-se os valores de taxa de transferência de oxigênio (TTO2) e de taxa de transferência de gás carbônico (TTCO2), hemoglobina sérica (HBS) e livre (HBL), plaquetometria, leucometria e taxa de transferência de calor. Resultados: Houve adequadas TTO2 e TTCO2. A lesão da maioria dos elementos figurados do sangue foi insignificante, sem alterações dos níveis de HBS, HBL, plaquetas e o número de leucócitos diminuíram com o tempo. A troca de calor foi efetiva (p ≤ 0,05). Conclusão: O oxigenador de membrana infantil OXM-1500, testado em ovinos, mostrou-se com capacidade adequada de oxigenação, remoção de gás carbônico e pequena alteração da hemoglobina e plaquetas, com diminuição do número de leucócitos de forma esperada. O trocador de calor acoplado ao oxigenador foi eficaz nas variações de temperatura.

O presente trabalho teve por finalidade estudar as alterações do sistema circulatório provocadas pela cirurgia cardíaca sob circulação extracorpórea, 12 pacientes adultos, anestesiados e curarizados, selecionados aleatoriamente, sendo 6 deles valvopatas e 6 coronariopatas. As alterações respiratórias foram verificadas por medidas da mecânica respiratória e da ventilação-oxigenação pulmonar. Do ponto de vista mecânico, o sistema respiratório foi analisado como um todo e individualizando os seus componentes - pulmões e parede torácica, tanto do ponto de vista elástico como também fluxo-resistivo. A análise das propriedades resistivas do sistema respiratório foi feita através de um método que se utiliza da insuflação pulmonar com fluxo constante, seguida de uma oclusão súbita das vias aéreas. Esta análise permite que tanto para o sistema respiratório como também para os pulmões e parede torácica, obtenha-se o valor resistivo máximo (Rmax) bem como o valor mínimo da resistência (Rmin) ao lado das resistências geradas pelas desigualdades do sistema (Ru). Este estudo foi feito graças a estimativa das diferentes respostas de frequência de cada um destes componentes. As medidas de ventilação-oxigenação foram aferidas pelo cálculo do \"shunt\" pulmonar (Qs/Q) e gradiente alvéolo-arterial de oxigenio P(A-a)O2. Tanto as medidas mecânicas como as de ventilação-oxigenação foram feitas na vigência de uma fração inspirada de O2 de 100% e realizadas de 15 a 30 minutos após a entubação traqueal, sendo repetidas logo após o fechamento do tórax. [...] / The aim of this work was to study the respiratory alterations caused by cardiac surgery under cardiopulmonary bypass in 12 randomly selected anesthetized paralyzed adult patients; 6 with acquired valvar disease and 6 with ischmic cardiopathy. Respiratory alterations were assessed by respiratory mechanics and lung ventilation-oxygenation measurements. Respiratory mechanics analyzed the respiratory system as a whole and partitioned into its components: lung and chest wall, measuring both the elastic and resistive properties were measured using a constant inflation flow followed bu a sudden occlusion. This analysis provides the maximum resistance value (Rmax), the minimum resistance value (Rmin), and the resistance caused by the uneven distribution of mechanical properties within the system (Ru), for respiratory system, lung and chest wall. This analysis is based on the frequency dependence differences of each component of respiratory system. The ventilation-oxygenation evaluation was done by the calculation of pulmonary shunt and the alveolar arterial oxygen gradient (P (A-a)O2). Both mechanical and ventilation-oxygenation measurement were done with a oxygen inspired fraction of 1 and performed 15 to 30 minutes after tracheal intubation and repeated just after thorax closure. [...]

Introdução: O diagnóstico infarto do miocárdio (IAM) Tipo 5 é bastante complexo, especialmente após o surgimento de ensaios com a troponina de alta sensibilidade. Objetivo: Mensurar a liberação de biomarcadores de necrose miocárdica após cirurgia de revascularização (RM) utilizando a circulação extracorpórea (CEC) na ausência de novo realce tardio pelo gadolínio (RTG). Métodos: Neste estudo, avaliamos pacientes com doença arterial coronária estável, multiarterial, função do ventrículo esquerdo preservada, biomarcadores cardíacos basais normais e indicação formal para a cirurgia de revascularização eletiva com CEC. Eletrocardiograma, coleta de amostras de sangue para a mensuração de troponina e CKMB, e ressonância magnética cardíaca (RMC) com realce tardio pelo gadolíneo (RTG) foram efetuadas antes e após o procedimento. O diagnóstico de IM foi definido como acima de 10 vezes o percentil 99 URL, para troponina e CK-MB, respectivamente, e novo RTG pela RMC. Resultados: De 75 pacientes selecionados para RM com CEC, 69 foram analisados; destes, 54 não apresentaram RTG (IAM tipo 5 na RMC). 39 pacientes eram do sexo masculino (72,2%), com idade média de 61,3 (±8,3) anos. A pontuação média do SYNTAX Score foi de 28 (±10). Após a cirurgia, 54 (100%) pacientes tiveram um pico de troponina acima do percentil 99; destes, em 52 (96%) este pico foi maior do que 10 vezes o percentil 99. Por outro lado, 54 (100%) pacientes alcançaram pico de CK-MB acima do limite do percentil 99 e em apenas 13 (24%) foi maior do que 10 vezes o percentil 99. A troponina apresentou mediana do pico de 3,15 (2,0 - 4,9) ng/mL, 78,75x superior ao percentil 99. Conclusão: Nesta amostra estudada, a CKMB, diferentemente da troponina, teve níveis de liberação dentro dos padrões recomendados pelas diretrizes e coincidiu com ausência de realce na RMC. Estes dados permitem sugerir um maior ponto de corte de troponina para o diagnóstico do IAM relacionado ao procedimento / Background: The diagnosis of periprocedural myocardial infarction is complex, especially after the emergence of high-sensitive markers of myocardial necrosis. Methods: In this prospective study, patients with stable multivessel coronary disease, preserved left ventricular function, normal baseline cardiac biomarkers, and formal indication for elective on-pump coronary bypass surgery (ONCAB) were evaluated. Electrocardiograms, cardiac biomarkers CKMB and troponin I (cTnI), and cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement were performed before and after procedures. Myocardial infarction (MI) was defined as more than ten times the upper reference limit of the 99th percentile for cTnI and for CKMB and by the findings of new late gadolinium enhancement on CMR. We assessed the release of cardiac biomarkers in patients with no evidence of myocardial infarction on CMR. Results: From 75 patients referred to ONCAB, 69 were analyzed in this study. From these, 54 patients did not have evidence of MI on CMR. This group had 39 men (72.2%), mean age of 61.3 (± 8.3) years and a mean SYNTAX Score of 28 (± 10). After CABG, all 54 (100%) patients had a peak cTnI above the 99th percentile, and 52 (96%) had an elevation 10 times higher than the 99th percentile. Regarding CKMB, 54 (100%) patients had a peak CKMB above the 99th percentile limit, and only 13 (24%) had an elevation greater than 10 times the 99th percentile. The median value of cTnI peak was 3.15 (2.0 to 4.9) ng/mL. This represented 78.75 times the 99th percentile. Conclusion: In this sample, CKMB, unlike cTnI, had levels of release within the standards recommended by the guidelines and coincided with lack of enhancement in CMR. These data suggest a higher troponin cutoff point for the diagnosis of MI related to the procedure

O presente trabalho teve por finalidade estudar as alterações do sistema circulatório provocadas pela cirurgia cardíaca sob circulação extracorpórea, 12 pacientes adultos, anestesiados e curarizados, selecionados aleatoriamente, sendo 6 deles valvopatas e 6 coronariopatas. As alterações respiratórias foram verificadas por medidas da mecânica respiratória e da ventilação-oxigenação pulmonar. Do ponto de vista mecânico, o sistema respiratório foi analisado como um todo e individualizando os seus componentes - pulmões e parede torácica, tanto do ponto de vista elástico como também fluxo-resistivo. A análise das propriedades resistivas do sistema respiratório foi feita através de um método que se utiliza da insuflação pulmonar com fluxo constante, seguida de uma oclusão súbita das vias aéreas. Esta análise permite que tanto para o sistema respiratório como também para os pulmões e parede torácica, obtenha-se o valor resistivo máximo (Rmax) bem como o valor mínimo da resistência (Rmin) ao lado das resistências geradas pelas desigualdades do sistema (Ru). Este estudo foi feito graças a estimativa das diferentes respostas de frequência de cada um destes componentes. As medidas de ventilação-oxigenação foram aferidas pelo cálculo do \"shunt\" pulmonar (Qs/Q) e gradiente alvéolo-arterial de oxigenio P(A-a)O2. Tanto as medidas mecânicas como as de ventilação-oxigenação foram feitas na vigência de uma fração inspirada de O2 de 100% e realizadas de 15 a 30 minutos após a entubação traqueal, sendo repetidas logo após o fechamento do tórax. [...] / The aim of this work was to study the respiratory alterations caused by cardiac surgery under cardiopulmonary bypass in 12 randomly selected anesthetized paralyzed adult patients; 6 with acquired valvar disease and 6 with ischmic cardiopathy. Respiratory alterations were assessed by respiratory mechanics and lung ventilation-oxygenation measurements. Respiratory mechanics analyzed the respiratory system as a whole and partitioned into its components: lung and chest wall, measuring both the elastic and resistive properties were measured using a constant inflation flow followed bu a sudden occlusion. This analysis provides the maximum resistance value (Rmax), the minimum resistance value (Rmin), and the resistance caused by the uneven distribution of mechanical properties within the system (Ru), for respiratory system, lung and chest wall. This analysis is based on the frequency dependence differences of each component of respiratory system. The ventilation-oxygenation evaluation was done by the calculation of pulmonary shunt and the alveolar arterial oxygen gradient (P (A-a)O2). Both mechanical and ventilation-oxygenation measurement were done with a oxygen inspired fraction of 1 and performed 15 to 30 minutes after tracheal intubation and repeated just after thorax closure. [...]

A medida da atividade do CYP2D6 in vivo pode ser estimada através do teste da debrisoquina pela administração de dose única PO do Declinax®, Roche, contendo 10 mg de sulfato de debrisoquina. Tal medida envolve coleta de urina e determinação da debrisoquina (D) e da 4-hidroxidebrisoquina (4-OHD). Para tanto, desenvolveu-se análise simultânea da D e da 4-OHD em urina através de cromatografia líquida de alta eficiência com detecção por fluorescência alcançando boa sensibilidade, especificidade e reprodutibilidade. Efetuou-se a validação da metodologia analítica pela aplicação do Teste a um voluntário sadio que foi caracterizado como metabolizador extensivo (EM). Realizou-se a seguir estudo piloto para a validação do teste da debrisoquina e aplicação na fenotipagem dos pacientes cardíacos. Desta forma, o protocolo de estudo constou da administração de dose única PO do Declinax® nos períodos pré- e pós-operatório de pacientes com indicação cirúrgica utilizando circulação extracorpórea e hipotermia, CEC-H. Todos os pacientes foram caracterizados como metabolizadores extensivos embora a capacidade de hidroxilação se encontrasse reduzida em cerca de 40% no 1ºPO, provavelmente pelas alterações hemodinâmicas ocorridas nestes pacientes, função da extensa manipulação pela intervenção cirúrgica. Dentre a medicação prescrita a esses pacientes internados, escolheu-se o propranolol, fármaco biotransformado pelo CYP2D6. Dada a ampla utilização na Clínica, apesar da redução empírica da dose no pós-operatório de cirurgia cardíaca, registraram-se baixo débito, redução da freqüência cardíaca e parada cardiorespiratória para este fármaco. Com a finalidade de se justificar convenientemente a redução da dose de propranolol no 1ºPO e investigar tais conseqüências no paciente cirúrgico após a extubação, propôs-se paralelamente a modelagem cinética do propranolol no transoperatório. Investigaram-se 15 pacientes coronarianos, metabolizadores extensivos pelo teste da debrisoquina, com indicação de cirurgia de revascularização CEC-H. Realizou-se a modelagem cinética através da coleta de duas amostras sangüíneas (pico e vale) em ambos os períodos Adicionalmente, colheram-se ainda amostras no intra- e pós-operatório imediato. Apesar da suspensão da medicação no dia que precedeu a cirurgia, evidenciaram-se concentrações de propranolol mensuráveis até o início do 1ºPO. Desta forma sugere-se que a manutenção dos níveis de propranolol seja devida a mobilização do fármaco do compartimento profundo, decorrência da lipólise modulada pelas catecolaminas elevadas pelo trauma e estresse cirúrgico. Os pacientes apresentaram no pós-operatório redução da depuração em cerca de 42%, aumento do volume de distribuição em 2,2 vezes, e prolongamento da meia-vida em cerca de 3 vezes. Com base nos resultados obtidos, considera-se fundamental a aplicação do teste da debrisoquina para a fenotipagem do paciente cardíaco e previsão da capacidade de hidroxilação uma vez que se demonstrou importante redução da biotransformação do propranolol e mobilização do fármaco de sítios de armazenamento. / Abstract not available.

<p>Nitric oxide (NO) is expressed in inflammatory tissues. However, NO effects are controversial in inflammation; NO is described as acting in a dose dependent manner and possess both pro-inflammatory and anti-inflammatory properties. </p><p>The present thesis explored the role of NO in relation to white blood cell (WBC) and protein system activation by foreign surfaces in simulated extracorporeal circulation (SECC) using human whole blood from volunteer donors. Three doses of NO, 40 ppm, 80 ppm and 500 ppm, were administered and an array of markers of WBC and protein activation were studied. Neutrophil degranulation was detected with myeloperoxidase (MPO), human neutrophil lipocalin (HNL) and lactoferrin (LF); eosinophil degranulation with eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO); and basophil degranulation with histamine. Furthermore, whole blood and WBC capacity to produce reactive oxygen species (ROS) were studied and cytokine release was measured with IL-1 and IL-10. Complement activation was measured with C3a and C5b-9 complex and contact system activation with FXIIa-C1INH, FXIIa-AT, FXIa-C1INH and FXIa-AT.</p><p>NO increased neutrophil degranulation at all dose levels and 80 ppm NO increased basophil degranulation; whereas, NO exerted no effect on eosinophil degranulation, WBC subset counts, cytokine release or capacity to produce ROS. In addition, while increasing both specific and azurophil degranulation with 40 ppm, 80 ppm and 500 ppm, NO reversed the classical degranulation hierarchy with 500 ppm and azurophil degranulation became predominant. Furthermore, NO effect was greater with 500 ppm than with 80 ppm, indicating a dose response effect. The lack of iNOS mRNA expression in WBC and lack of L-NAME effect on degranulation and nitrite/nitrate production, together with absent increase in nitrite/nitrate in controls, excluded autocrine or paracrine regulation of degranulation. FXIIa-AT and FXIa-AT complexes increased and became predominant during early recirculation, whereas FXIIa-C1INH and FXIa-C1INH complexes were predominant at baseline but remained unaltered, suggesting contact system inhibition predominantly via AT. C3a and C5b-C9 increased. NO had no effect on either contact or complement system activation; however, 500 ppm NO shortened active clotting time.</p><p>In conclusion, the present data suggest that NO has a direct effect on neutrophil and basophil degranulation. Recognition of NO as an enhancer of degranulation may give access to new therapeutic tools for local and systemic inflammatory therapies; whereas, the identification of increased AT mediated inhibition of FXIIa and unchanged C1INH complexes presents new possibilities for therapeutic intervention in conditions such as hereditary angioedema and heart surgery.</p>

Nitric oxide (NO) is expressed in inflammatory tissues. However, NO effects are controversial in inflammation; NO is described as acting in a dose dependent manner and possess both pro-inflammatory and anti-inflammatory properties. The present thesis explored the role of NO in relation to white blood cell (WBC) and protein system activation by foreign surfaces in simulated extracorporeal circulation (SECC) using human whole blood from volunteer donors. Three doses of NO, 40 ppm, 80 ppm and 500 ppm, were administered and an array of markers of WBC and protein activation were studied. Neutrophil degranulation was detected with myeloperoxidase (MPO), human neutrophil lipocalin (HNL) and lactoferrin (LF); eosinophil degranulation with eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO); and basophil degranulation with histamine. Furthermore, whole blood and WBC capacity to produce reactive oxygen species (ROS) were studied and cytokine release was measured with IL-1 and IL-10. Complement activation was measured with C3a and C5b-9 complex and contact system activation with FXIIa-C1INH, FXIIa-AT, FXIa-C1INH and FXIa-AT. NO increased neutrophil degranulation at all dose levels and 80 ppm NO increased basophil degranulation; whereas, NO exerted no effect on eosinophil degranulation, WBC subset counts, cytokine release or capacity to produce ROS. In addition, while increasing both specific and azurophil degranulation with 40 ppm, 80 ppm and 500 ppm, NO reversed the classical degranulation hierarchy with 500 ppm and azurophil degranulation became predominant. Furthermore, NO effect was greater with 500 ppm than with 80 ppm, indicating a dose response effect. The lack of iNOS mRNA expression in WBC and lack of L-NAME effect on degranulation and nitrite/nitrate production, together with absent increase in nitrite/nitrate in controls, excluded autocrine or paracrine regulation of degranulation. FXIIa-AT and FXIa-AT complexes increased and became predominant during early recirculation, whereas FXIIa-C1INH and FXIa-C1INH complexes were predominant at baseline but remained unaltered, suggesting contact system inhibition predominantly via AT. C3a and C5b-C9 increased. NO had no effect on either contact or complement system activation; however, 500 ppm NO shortened active clotting time. In conclusion, the present data suggest that NO has a direct effect on neutrophil and basophil degranulation. Recognition of NO as an enhancer of degranulation may give access to new therapeutic tools for local and systemic inflammatory therapies; whereas, the identification of increased AT mediated inhibition of FXIIa and unchanged C1INH complexes presents new possibilities for therapeutic intervention in conditions such as hereditary angioedema and heart surgery.

Das Auftreten manifester transplantationsassoziierter thrombotischer Mikroangiopathie sowie das Auftreten leichterer, zumeist subklinischer mikroangiopathischer Veränderungen wurde in einem Kollektiv von Patienten untersucht, die zur Behandlung einer steroidrefraktären oder abhängigen akuten oder chronischen GvHD nach allogener Stammzelltransplantation eine Therapie mit extrakorporalen Photopheresen erhielten. Subklinische mikroangiopathische Schädigung wurde durch ein auf den Messwerten von Fragmentozyten, Thrombozyten sowie der LDH-Aktivität beruhendes Bewertungsschema festgestellt. Das Auftreten von ausgeprägten mikroangiopathischen Veränderungen (Schweregrad 2) ging mit einem erniedrigten Gesamtüberleben einher. Die Reduktion der Steroiddosis und die Verringerung der GvHD-Manifestationen wurden als Parameter für die Wirksamkeit der ECP analysiert. Ihre Effektivität wurde bestätigt. Trotz der nachgewiesenen Effektivität der ECP in der Kontrolle der GvHD zeigte sich eine Tendenz zur Zunahme mikroangiopathischer Veränderungen unter Therapie mit ECP, in Einzelfällen mit schwerwiegenden klinischen Konsequenzen.

Introduction : L’hypothermie accidentelle est associée à un taux important de morbidité et de mortalité, notamment en cas d’hypothermie accidentelle sévère où le risque d’arrêt cardiaque est très élevé. L’Extracorporeal Life Support (ECLS) est le traitement de référence dans le cas d’hypothermie avec arrêt cardiaque ou instabilité hémodynamique réfractaire. Il n’existe pas de recommandations concernant les modalités optimales de réchauffement.L’objectif de ce travail était de développer un modèle expérimental porcin d’arrêt cardiaque en hypothermie profonde afin d’étudier la réponse physiopathologique cardiaque et pulmonaire pendant le refroidissement et le réchauffement par ECLS. Nous avons également évalué l’impact de différentes stratégies de réchauffement (en terme de débit d’ECLS et de delta de température entre l’ECLS et la température centrale) sur les lésions cardiaques et pulmonaires.Méthode : Deux protocoles expérimentaux ont été réalisés. Les animaux ont été canulés pour ECLS, refroidis jusqu’à l’obtention d’un arrêt cardiaque (AC) en hypothermie profonde et soumis à 30 minutes d’ischémie complète. Protocole A (n = 24) : durant la phase de réchauffement, les animaux étaient randomisés en 4 groupes selon un plan factoriel 2x2 comparant un débit normal d’ECLS de 3l/min (groupe NF) à un débit réduit de 1,5 l/min (groupe LF) ainsi qu’un delta de température entre la température centrale et le circuit d’ECLS limité à 5°C, ou une température d’ECLS à 38°C. Protocole B (n = 20) : les animaux ont été randomisés en 2 groupes pendant le réchauffement : un groupe NF et un groupe LF avec un delta de température de 5°C. L’impact de l’ECLS sur le débit cardiaque en fin de réchauffement a été évalué par une technique de thermodilution (site d’injection du catheter positionné dans le ventricule droit) et contrôlé par une technique écho-doppler. Le débit cardiaque, l’hémodynamique et des paramètres de fonction pulmonaire étaient évalués. Des marqueurs biologiques de lésions d’ischémie/reperfusion étaient mesurés.Résultats : Protocole A : Le débit cardiaque final était réduit dans les groupes LF comparé aux groupes NF (1.96±1.4 vs. 3.34±1.7 L/min, p=0.05). L’augmentation de RAGE était plus élevée dans les groupes avec une température d’ECLS à 38°C comparée aux groupes avec delta contrôlé. Protocole B : Durant la phase de refroidissement, le débit cardiaque, la fréquence cardiaque et la pression artérielle ont diminué de façon continue. La pression artérielle pulmonaire avait tendance à augmenter à 32°c comparée à la valeur initiale (20.2±1.7 vs. 29.1±5.6 mmHg, p=0.09). Pendant le réchauffement, la pression artérielle moyenne était plus élevée dans le groupe NF vs. groupe LF à 20°C et 25°C (p=0.003 and 0.05, respectivement). Après réchauffement à 35°C, le débit cardiaque était de 3.9±0.5L/min dans le groupe NF vs. 2.7±0.5 L/min dans le groupe LF (p=0.06). Sous ECLS, le débit cardiaque gauche était inversement proportionnel au débit d’ECLS. En fin de réchauffement, le débit ECLS n’avait pas d’impact significatif sur les résistances pulmonaires.Conclusion : Nos résultats suggèrent que le réchauffement par ECLS des arrêts cardiaques en hypothermie profonde, en utilisant un débit d’ECLS normal avec un delta de température n’excédant pas 5°C par rapport à la température centrale, pourrait être la stratégie la moins délétère au niveau cardiaque et pulmonaire. L’ECLS à débit normal diminuait la dysfonction myocardique en fin de réchauffement et ne majorait pas les résistances vasculaires pulmonaires par rapport au groupe avec un débit d’ECLS réduit. Un delta important entre la température centrale et celle de l’ECLS augmentait le taux du biomarqueur associés aux lésions pulmonaires. Ce modèle expérimental apporte des éléments physiopathologiques dans le choix des modalités de réchauffement des patients victimes d’hypothermie accidentelle profonde et pourrait permettre d’évaluer d’autres stratégies thérapeutiques dans ce contexte. / Introduction: Accidental hypothermia is associated with significant mortality and morbidity, especially when core temperature is under 28°C with an increased risk of cardiac arrest. Extracorporeal life support (ECLS) is the preferred treatment in case of cardiac arrest or hemodynamic instability not responding to medical treatment. There are no current guidelines concerning the optimal rewarming strategy. The aim of this work was to develop a porcine experimental model of deep hypothermic cardiac arrest (DHCA) in order to assess the cardiac and pulmonary pathophysiological response during cooling and rewarming with ECLS. We also aimed to assess the impact of different ECLS blood flow rates on cardiopulmonary lesions.Method: Two experimental protocols were performed. Pigs were cannulated for ECLS, cooled until DHCA occurred and subjected to 30 min of cardiac arrest. Protocol A (n = 24): during the rewarming phase, pigs were randomized into 4 groups with 2X2 factorial design. We compared a low blood flow rate of 1.5 L/min (group LF) vs. a normal flow rate of 3.0 L/min (group NF) and a temperature during ECLS adjusted to 5°C above the central core temperature vs. 38°C maintained throughout the rewarming phase. Protocol B (n = 20): Animals were also randomized in 2 groups during rewarming, a group NF and a group LF with a controlled temperature delta of 5°C. In order to assess the physiological impact of ECLS on cardiac output at the end of rewarming we measured flow in the pulmonary artery using a modified thermodilution technique using the Swan-Ganz catheter (injection site inserted in the right ventricle) controlled also by an echocardiographic measurement. Cardiac output, hemodynamics and pulmonary function parameters were evaluated. Biological markers of ischemia/reperfusion injuries were analyzed.Results: Protocol A : The final cardiac output was reduced in the low flow rate versus the high flow rate groups (1.96±1.4 versus 3.34±1.7 L/min, p=0.05). The increase in the serum RAGE concentration was higher in the 38°C rewarming temperature groups compared to 5°C above adjusted temperature.Protocol B: During the cooling phase, cardiac output, heart rhythm, and blood pressure decreased continuously. Pulmonary artery pressure tended to increase at 32°C compared to initial value (20.2 ± 1.7 vs. 29.1 ± 5.6 mmHg, p=0.09). During rewarming, arterial blood pressure was higher at 20° and 25°C in group NF vs. Group LF (p=0.003 and 0.05, respectively). After rewarming at 35°C, cardiac output was 3.9 ± 0.5 in the group NF vs. 2.7 ± 0.5 L/min in group LF (p=0.06). Under ECLS cardiac output was inversely proportional to ECLS flow rate. ECLS flow rate did not significantly change pulmonary vascular resistance.Conclusion: Our results suggest that ECLS rewarming for DHCA patients, using a normal inflow rate of ECLS and a controlled temperature with less than 5°C between ECLS and core temperature could be the less deleterious rewarming strategy to limit cardiac and pulmonary dysfunction. A normal inflow rate of ECLS decreased cardiac dysfunction after rewarming and did not increased pulmonary vascular resistance compared to a low flow rate. A non controlled temperature delta between core temperature and ECLS increased biomarkers level of lung injury. This experimental model on pigs bring some pathophysiological finding for the rewarming strategy of patients who suffer deep accidental hypothermia and could allow to assess different therapeutic strategy in this context.