Des éléments contributifs à plusieurs facettes de la chirurgie cardiaque ont été étudiés dans la présente thèse. Le premier manuscrit adresse la problématique de l’accident cérébro-vasculaire (ACV) post-opératoire. Nous avons analysé de façon rétrospective la médication prise en pré-opératoire de 6813 patients nécessitant une chirurgie de revascularisation coronarienne. Le but étant d’établir si la présence d’une médication précise (aspirine, inhibiteur de l’enzyme de conversion de l’angiotensine, statine, bêta-bloqueur) peut agir en pré-opératoire pour diminuer le risque d’ACV. En analyse multivariée, la combinaison de la prise de bêta-bloqueurs avec une statine a produit un ratio de cote de 0,37, suggérant un effet protecteur très important. Dans le deuxième manuscrit, je présente une étude ciblant les patients avec insuffisance mitrale ischémique modérée. Trente et un patients furent randomisés entre un traitement par pontages seuls vs pontages et annuloplastie mitrale restrictive. L’insuffisance mitrale a disparu en post-opératoire immédiat en présence de l’annuloplastie alors qu’aucun effet immédiat de la revascularisation coronarienne n’était noté sur l’insuffisance mitrale. Un an suivant la chirurgie, une insuffisance mitrale légère est réapparue chez le groupe ayant subi l’annuloplastie alors que les patients du groupe pontages seuls ont remodelé leur ventricule gauche et diminué l’importance de leur insuffisance mitrale au même niveau que le groupe annuloplastie. Aucun des marqueurs d’évolution clinique, tant au niveau symptomatique qu’au niveau de la survie ne diffère entre les groupes. La troisième étude est un suivi sur 20 ans des patients ayant eu des remplacements valvulaires mitraux ou aortiques avec une prothèse mécanique Carbomedics. Cette étude démontre une excellente survie avec un taux de complications valvulaires hémorragiques, thrombotiques, thrombo-emboliques, et d’endocardite favorable comparé aux autres types de prothèse et une absence de bris mécanique. / Many aspects of heart surgery have been carefully studied in the present thesis. The first manuscript touches the important problematic of post-operative stroke. We have analysed in a retrospective fashion the prescription drugs taken pre-operatively in 6,813 patients requiring coronary artery bypass surgery. The aim was to analyse the effect of taking any of the following medications pre-operatively on the risk of post-operative stroke: aspirin, agiotension converting enzyme (ACE) inhibitors, statins, beta-blockers. The combination of taking a beta-blocker and a statin yielded an odd ratio of 0.37 in multivariable analysis, suggesting a strong protective effect. In the second manuscript, I present a study addressing the problematic of moderate ischemic mitral regurgitation. We randomized 31 patients to be treated either by coronary bypass grafts alone or by a combination of coronary bypass grafting and restrictive mitral annuloplasty. Mitral valve regurgitation disappeared immediately following surgery in the annuloplasty group while no impact of coronary artery bypass graft (CABG) alone was noted on mitral insufficiency at the same time point. After one year of follow-up, mild mitral insufficiency was noted to recur in the annuloplasty group while the patients from the CABG alone group remodelled their left ventricle and secondarily decreased their mitral insufficiency grade to the same level as the annuloplasty group. None of the different measurements of clinical evolution differed between the groups at one year. The third study is a 20-year follow-up of patients who had an isolated valvular replacement on the aortic or mitral position with the Carbomedics mechanical prosthesis. This study shows an excellent survival rate with low complications of hemorrhage, thrombosis, thrombo-embolism, reoperation and endocarditis. Noteworthy, a complete absence of structural failure at 20 years.

La fibrillation auriculaire (FA) est une arythmie touchant les oreillettes. En FA, la contraction auriculaire est rapide et irrégulière. Le remplissage des ventricules devient incomplet, ce qui réduit le débit cardiaque. La FA peut entraîner des palpitations, des évanouissements, des douleurs thoraciques ou l’insuffisance cardiaque. Elle augmente aussi le risque d'accident vasculaire. Le pontage coronarien est une intervention chirurgicale réalisée pour restaurer le flux sanguin dans les cas de maladie coronarienne sévère. 10% à 65% des patients qui n'ont jamais subi de FA, en sont victime le plus souvent lors du deuxième ou troisième jour postopératoire. La FA est particulièrement fréquente après une chirurgie de la valve mitrale, survenant alors dans environ 64% des patients. L'apparition de la FA postopératoire est associée à une augmentation de la morbidité, de la durée et des coûts d'hospitalisation. Les mécanismes responsables de la FA postopératoire ne sont pas bien compris. L'identification des patients à haut risque de FA après un pontage coronarien serait utile pour sa prévention. Le présent projet est basé sur l'analyse d’électrogrammes cardiaques enregistrées chez les patients après pontage un aorte-coronaire. Le premier objectif de la recherche est d'étudier si les enregistrements affichent des changements typiques avant l'apparition de la FA. Le deuxième objectif est d'identifier des facteurs prédictifs permettant d’identifier les patients qui vont développer une FA. Les enregistrements ont été réalisés par l'équipe du Dr Pierre Pagé sur 137 patients traités par pontage coronarien. Trois électrodes unipolaires ont été suturées sur l'épicarde des oreillettes pour enregistrer en continu pendant les 4 premiers jours postopératoires. La première tâche était de développer un algorithme pour détecter et distinguer les activations auriculaires et ventriculaires sur chaque canal, et pour combiner les activations des trois canaux appartenant à un même événement cardiaque. L'algorithme a été développé et optimisé sur un premier ensemble de marqueurs, et sa performance évaluée sur un second ensemble. Un logiciel de validation a été développé pour préparer ces deux ensembles et pour corriger les détections sur tous les enregistrements qui ont été utilisés plus tard dans les analyses. Il a été complété par des outils pour former, étiqueter et valider les battements sinusaux normaux, les activations auriculaires et ventriculaires prématurées (PAA, PVA), ainsi que les épisodes d'arythmie. Les données cliniques préopératoires ont ensuite été analysées pour établir le risque préopératoire de FA. L’âge, le niveau de créatinine sérique et un diagnostic d'infarctus du myocarde se sont révélés être les plus importants facteurs de prédiction. Bien que le niveau du risque préopératoire puisse dans une certaine mesure prédire qui développera la FA, il n'était pas corrélé avec le temps de l'apparition de la FA postopératoire. Pour l'ensemble des patients ayant eu au moins un épisode de FA d’une durée de 10 minutes ou plus, les deux heures précédant la première FA prolongée ont été analysées. Cette première FA prolongée était toujours déclenchée par un PAA dont l’origine était le plus souvent sur l'oreillette gauche. Cependant, au cours des deux heures pré-FA, la distribution des PAA et de la fraction de ceux-ci provenant de l'oreillette gauche était large et inhomogène parmi les patients. Le nombre de PAA, la durée des arythmies transitoires, le rythme cardiaque sinusal, la portion basse fréquence de la variabilité du rythme cardiaque (LF portion) montraient des changements significatifs dans la dernière heure avant le début de la FA. La dernière étape consistait à comparer les patients avec et sans FA prolongée pour trouver des facteurs permettant de discriminer les deux groupes. Cinq types de modèles de régression logistique ont été comparés. Ils avaient une sensibilité, une spécificité et une courbe opérateur-receveur similaires, et tous avaient un niveau de prédiction des patients sans FA très faible. Une méthode de moyenne glissante a été proposée pour améliorer la discrimination, surtout pour les patients sans FA. Deux modèles ont été retenus, sélectionnés sur les critères de robustesse, de précision, et d’applicabilité. Autour 70% patients sans FA et 75% de patients avec FA ont été correctement identifiés dans la dernière heure avant la FA. Le taux de PAA, la fraction des PAA initiés dans l'oreillette gauche, le pNN50, le temps de conduction auriculo-ventriculaire, et la corrélation entre ce dernier et le rythme cardiaque étaient les variables de prédiction communes à ces deux modèles. / Atrial fibrillation (AF) is an abnormal heart rhythm (cardiac arrhythmia). In AF, the atrial contraction is rapid and irregular, and the filling of the ventricles becomes incomplete, leading to reduce cardiac output. Atrial fibrillation may result in symptoms of palpitations, fainting, chest pain, or even heart failure. AF is an also an important risk factor for stroke. Coronary artery bypass graft surgery (CABG) is a surgical procedure to restore the perfusion of the cardiac tissue in case of severe coronary heart disease. 10% to 65% of patients who never had a history of AF develop AF on the second or third post CABG surgery day. The occurrence of postoperative AF is associated with worse morbidity and longer and more expensive intensive-care hospitalization. The fundamental mechanism responsible of AF, especially for post-surgery patients, is not well understood. Identification of patients at high risk of AF after CABG would be helpful in prevention of postoperative AF. The present project is based on the analysis of cardiac electrograms recorded in patients after CABG surgery. The first aim of the research is to investigate whether the recordings display typical changes prior to the onset of AF. A second aim is to identify predictors that can discriminate the patients that will develop AF. Recordings were made by the team of Dr. Pierre Pagé on 137 patients treated with CABG surgery. Three unipolar electrodes were sutured on the epicardium of the atria to record continuously during the first 4 post-surgery days. As a first stage of the research, an automatic and unsupervised algorithm was developed to detect and distinguish atrial and ventricular activations on each channel, and join together the activation of the different channels belonging to the same cardiac event. The algorithm was developed and optimized on a training set, and its performance assessed on a test set. Validation software was developed to prepare these two sets and to correct the detections over all recordings that were later used in the analyses. It was complemented with tools to detect, label and validate normal sinus beats, atrial and ventricular premature activations (PAA, PVC) as well as episodes of arrhythmia. Pre-CABG clinical data were then analyzed to establish the preoperative risk of AF. Age, serum creatinine and prior myocardial infarct were found to be the most important predictors. While the preoperative risk score could to a certain extent predict who will develop AF, it was not correlated with the post-operative time of AF onset. Then the set of AF patients was analyzed, considering the last two hours before the onset of the first AF lasting for more than 10 minutes. This prolonged AF was found to be usually triggered by a premature atrial PAA most often originating from the left atrium. However, along the two pre-AF hours, the distribution of PAA and of the fraction of these coming from the left atrium was wide and inhomogeneous among the patients. PAA rate, duration of transient atrial arrhythmia, sinus heart rate, and low frequency portion of heart rate variability (LF portion) showed significant changes in last hour before the onset of AF. Comparing all other PAA, the triggering PAA were characterized by their prematurity, the small value of the maximum derivative of the electrogram nearest to the site of origin, as well as the presence of transient arrhythmia and increase LF portion of the sinus heart rate variation prior to the onset of the arrhythmia. The final step was to compare AF and Non-AF patients to find predictors to discriminate the two groups. Five types of logistic regression models were compared, achieving similar sensitivity, specificity, and ROC curve area, but very low prediction accuracy for Non-AF patients. A weighted moving average method was proposed to design to improve the accuracy for Non-AF patient. Two models were favoured, selected on the criteria of robustness, accuracy, and practicability. Around 70% Non-AF patients were correctly classified, and around 75% of AF patients in the last hour before AF. The PAA rate, the fraction of PAA initiated in the left atrium, pNN50, the atrio-ventricular conduction time, and the correlation between the latter and the heart rhythm were common predictors of these two models.

Made available in DSpace on 2016-06-02T20:19:06Z (GMT). No. of bitstreams: 1 1696.pdf: 3646825 bytes, checksum: e027c9b9c12baae91d504600ec364c3c (MD5) Previous issue date: 2008-02-28 / Universidade Federal de Sao Carlos / It is well-known that cardiac autonomic and pulmonary function are impaired after coronary artery bypass surgery (CABG). Strategies resulting in beneficial cardiorespiratory responses as soon as possible after surgery are clinically important in these patients. However, information on the differences in cardiorespiratory responses of these patients to inpatient cardiac rehabilitation (CR) with distinct left ventricular (LVF) is still scant. Therefore, the purpose of this study was to assess the cardiorespiratory responses to a short-term inpatient CR programme in patients with LVF normal and reduced. Twenty three patients were studied and divided into LVF normal group (LVFN, n=12) or reduced group (LVFR, n=11). Cardiac autonomic function was evaluated by heart rate variability (HRV) and the pulmonary function by spirometric and respiratory muscle strength (RMS) at (1) post-operative day 1 (PO1) and (2) day before discharge. Heart rate (HR) and R-R intervals (R-Ri) were recorded by telemetry system Polar S810i, at rest, in supine and sitting position. HRV was evaluated in time domain by mean R-R (mean R-R), square root of the mean squared differences of successive R-Ri (RMSSD) and standard deviation of all R-Ri (SDNN) indexes (ms) The spirometric data of vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and maximal voluntary ventilation (MVV) were obtained and the RMS was measured indirectly by maximal inspiratory (MIP) and expiratory (MEP) pressures. All patients initiated the CR on PO1 following a programme of progressive steps composed of whole body and breathing exercises previously established until discharge. Results: After inpatient CR, both groups presented improvement of mean R-R (ms) and RMSSD (ms) indexes at rest and beneficial response to postural change with lower RMSSD (ms) index in sitting position. Significant improvement of pulmonary function in both groups was observed to majority spirometric data as FVC, MVV and FEV1 and RMS only presented tend to improvement in response to CR programme Conclusions: These results indicate that patients undergoing CABG with preserved or depressed LVF presented beneficial cardiorespiratory responses to CR after surgery. We also assign slightly more favourable responses on autonomic function in those with depressed LVF without additional risks. Therefore, the inpatient whole CR should be strongly indicates as soon as possible post-CABG even in patients with cardiac dysfunction. Financial support: CNPq e FAPESP (05/59427-7). / É conhecido que a função autonômica cardíaca e pulmonar se encontram prejudicadas em pacientes submetidos à cirurgia de revascularização do miocárdio (CRM). Estratégias resultantes em respostas cardiorrespiratórias benéficas e implementadas tão cedo quanto possível no pós-CRM são clinicamente importantes a estes pacientes. No entanto, permanece escassa a informação sobre as possíveis diferenças nas respostas cardiorrespiratórias destes pacientes a reabilitação cardíaca (RC) hospitalar quando estes apresentam funções ventriculares distintas (normal ou reduzida). Portanto, o objetivo deste estudo foi avaliar as respostas cardiorrespiratórias a um programa de RC na fase hospitalar em pacientes com função ventricular esquerda (FVE) normal e reduzida. Foram estudados vinte e três pacientes divididos em: Grupo FVEN=12, composto de pacientes com FVE normal e Grupo FVER=11, composto de pacientes com FVE reduzida. A função autonômica cardíaca foi avaliada pela variabilidade da freqüência cardíaca (VFC) e a função pulmonar pelas variáveis espirométricas e medida de força muscular respiratória (FMR) no (1) primeiro dia pós-operatório (PO1) e (2) no dia anterior a alta hospitalar. A freqüência cardíaca (FC) e os intervalos R-R foram registrados pelo sistema de telemetria Polar S810i, em condições de repouso, nas posições supina e sentada. A VFC foi analisada no domínio do tempo pela média dos iR-R (média R-R), raiz quadrada da média do quadrado das diferenças entre intervalos RR normais adjacentes (RMSSD) e desvio-padrão da média de todos os intervalos R-R normais (SDNN) em milisegundos. Os dados espirométricos de capacidade vital (CV), capacidade vital forçada (CVF), volume expiratório forçado no 1º segundo (VEF1) e ventilação voluntária máxima (VVM) foram obtidos e a FMR foi medida indiretamente pelas pressões inspiratória (PImax) e expiratória (PEmax) máximas. Todos os pacientes iniciaram o programa de RC no PO1 seguindo um programa de etapas progressivas composto de exercícios globais e respiratórios previamente estabelecido até a alta hospitalar. Resultados: Após RC, ambos os grupos apresentaram melhora da média R-R (ms) e do índice RMSSD (ms) em repouso e respostas benéficas a mudança postural com menor valor do índice RMSSD (ms) na posição sentada. Foi encontrada melhora significativa da função pulmonar em ambos os grupos, observada para a maioria dos dados espirométricos como CVF, VVM e VEF1 e a FMR apresentou apenas tendência à melhora em reposta ao programa de RC. Conclusões: Estes resultados indicam que pacientes submetidos a CRM com FVE preservada ou reduzida apresentaram respostas cardiorrespiratórias benéficas a RC após a cirurgia. Atribuímos resposta mais favorável para função autonômica cardíaca para aqueles pacientes com FVE reduzida sem riscos adicionais. Portanto, um programa de RC global em ambiente hospitalar deve ser fortemente indicado tão o mais rapidamente possível pós-CRM mesmo em pacientes com disfunção cardíaca. Apoio financeiro: CNPq e FAPESP (05/59427-7).

Made available in DSpace on 2016-06-02T20:19:11Z (GMT). No. of bitstreams: 1 2553.pdf: 1596497 bytes, checksum: 1c1b091ddb6a8fb9d0cc5e1b5bfd8201 (MD5) Previous issue date: 2009-06-26 / Universidade Federal de Minas Gerais / Noninvasive positive pressure ventilation (NIPPV) has been commonly applied in several clinical and postoperative conditions, especially after coronary artery bypass grafting (CABG) surgery and it can cause breathing pattern (BP) alterations and mechanical effects on cardiovascular system, with cardiac autonomic adjustments. However, it is not well established in the literature how these alterations occur in patients submitted to the CABG and if they can be related to the application of different positive airway pressure levels. In this context, we considered the development of two studies that could contribute with new information about these topics. The first study is entitled Acute application of bilevel positive airway pressure influence cardiac autonomic nervous system and its objective was to evaluate the changes in heart rate variability (HRV) during bilevel positive airway pressure (Bilevel) application in healthy young men. Twenty men underwent a 10-min register of R-R intervals (R-Ri) during sham ventilation, Bilevel 8-15cmH2O and Bilevel 13-20 cmH2O. HRV was analyzed in time and frequency-domain and with non-linear statistical measures. Physiological variables (blood pressure, breathing rate, end tidal carbon dioxide- ETCO2) were also collected. R-Ri mean, rMSSD, NN50, pNN50 and SD1 reduced during 13-20 cmH2O compared to sham ventilation, with reduction of the R-Ri mean compared to 8-15 cmH2O. R-Ri mean and high frequency band (HF) reduced and low frequency band (LF) increased during 8-15 cmH2O compared to sham ventilation. Delta of ETCO2 correlated positively with LF, HF, LF/HF, SDNN, rMSSD and SD1. In conclusion, acute application of Bilevel was able to alter cardiac autonomic nervous system, with parasympathetic activity reduction and sympathetic increase and higher level of positive airway pressure can cause a greater influence on the cardiovascular and respiratory system. The second study is entitled The effects of different levels of positive airway pressure on respiratory pattern and heart rate variability in patients submitted to coronary artery bypass grafting surgery and its objective was to access the effects of different levels of continuous positive airway pressure (CPAP) in BP and HRV in CABG postoperative (PO), as well as the impact of CABG in these variables. Eighteen patients underwent CABG was evaluated during spontaneous breathing (SB) and four different CPAP levels of CPAP, in a random order: (a) CPAP = sham (3 cmH2O), (b) 5 CPAP = cmH2O, (c) 8 CPAP= cmH2O, (d) 12 CPAP = cmH2O in PO. HRV was analysed in time and frequency domain and by non-linear methods (Poincaré plot e Detrended Fluctuation Analysis) and BP was analysed by inductive respiratory plethysmograph. There were significant alterations of HRV and BP in the PO of CRM, compared to pre-operative and alterations of DFAα1, DFAα2 e SD2 and respiratory variables during NIPPV, with higher influence observed during application of the two higher levels applied. Moreover, there was relationship between DFAα1 and inspiratory time of delta 12 cmH2O and SB, and 8 cmH2O and SB. In conclusion, acute CPAP application was able to alter the control of cardiac autonomic nervous system and BP of patients submitted to CABG and higher levels promoted better performance of pulmonary and cardiac autonomic function. / A ventilação não-invasiva por pressão positiva (VNIPP) tem sido comumente utilizada em diversas condições clínicas e pós-operatórias, principalmente na cirurgia de revascularização do miocárdio (CRM) e pode causar alterações do padrão ventilatório (PV) e efeitos mecânicos sobre o sistema cardiovascular, com ajustes autonômicos cardíacos. Entretanto, ainda não é claro se estas alterações ocorrem em pacientes submetidos à CRM e se podem estar relacionadas a diferentes níveis pressóricos aplicados. Neste contexto, propusemos o desenvolvimento de dois estudos que poderiam contribuir com novas informações. O primeiro estudo, intitulado Aplicação aguda de pressão positiva por dois níveis pressóricos nas vias aéreas influencia o sistema nervoso autonômico cardíaco teve por objetivo avaliar as mudanças na variabilidade da frequência cardíaca (VFC) durante aplicação de pressão positiva por dois níveis pressóricos (Bilevel) em indivíduos jovens saudáveis. Vinte homens foram submetidos ao registro de 10 minutos dos intervalos R-R (iR-R) durante aplicação de ventilação sham, Bilevel 8- 15cmH2O e Bilevel 13-20 cmH2O. A VFC foi analisada no domínio do tempo e da freqüência e por métodos não-lineares. Variáveis fisiológicas (pressão arterial, frequência respiratória e fração de dióxido de carbono no final da expiração- ETCO2) também foram coletadas. Houve redução da média dos iR-R, e dos índices rMSSD, NN50, pNN50 e SD1 durante aplicação dos níveis 13-20 cmH2O de Bilevel comparado ao modo sham, ainda com redução da média dos iR-R quando comparados aos níveis 8-15cmH2O. Houve diminuição da média dos iR-R e da banda de alta freqüência (AF), com aumento da banda de baixa freqüência (BF) durante a aplicação de 8-15 cmH2O comparada à ventilação sham. O delta de ETCO2 correlacionou-se positivamente com BF, AF, BF/AF, SDNN, rMSSD e SD1. Em conclusão, a aplicação aguda de Bilevel foi capaz de alterar o sistema nervoso autonômico cardíaco, com redução da atividade parassimpática e aumento da atividade simpática e níveis mais elevados de pressão positiva podem causar maior influência nos sistemas cardiovascular e respiratório. O segundo estudo, intitulado Efeitos de diferentes níveis de pressão positiva nas vias aéreas sobre o padrão ventilatório e a variabilidade da freqüência cardíaca de pacientes submetidos à cirurgia de revascularização do miocárdio objetivou avaliar os efeitos da aplicação de diferentes níveis de pressão positiva contínua nas vias aéreas (CPAP) sobre o padrão ventilatório (PV) e a VFC no pós-operatório (PO) de CRM, bem como o impacto da CRM sobre estas variáveis. Foram avaliados 18 pacientes submetidos à CRM, durante RE (respiração espontânea) e aplicação de quatro níveis de CPAP, de forma randomizada: (a) CPAP = sham (3 cmH2O), (b) CPAP = 5 cmH2O, (c) CPAP= 8 cmH2O, (d) CPAP = 12 cmH2O no PO. A VFC foi analisada no domínio do tempo e da freqüência e por métodos não-lineares (Poincaré plot e Flutuações Depuradas de Tendência) e o PV foi analisado em diferentes variáveis, por meio da pletismografia respiratória por indutância. Houve alteração da VFC e do PV no PO de CRM, comparado ao período pré-operatório, bem como alterações dos índices DFAα1, DFAα2 e SD2, e de variáveis ventilatórias durante aplicação de VNIPP, com maior influência exercida pela aplicação dos dois níveis pressóricos mais elevados. Além disso, houve correlação entre o índice DFAα1 e tempo inspiratório para o delta de 12 cmH2O e RE, e 8 cmH2O e RE. Em conclusão, temos que a aplicação aguda de CPAP foi capaz de alterar o controle do sistema nervoso autonômico cardíaco e o PV de pacientes submetidos à CRM e os níveis mais elevados promoveram melhor desempenho da função pulmonar e autonômica cardíaca. Apoio Financeiro: FAPESP (07/53202-9).

Made available in DSpace on 2016-12-06T17:07:23Z (GMT). No. of bitstreams: 1 Kelly.pdf: 1033318 bytes, checksum: b10b8be25b6a3230a6d02542f0cf28a7 (MD5) Previous issue date: 2010-03-08 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Introduction: The coronary artery bypass graft is associated with deleterious effects on lung function and functional capacity in the immediate postoperative. Objective: To analyse the effects of a preoperative inspiratory muscle training (IMT) program on functional and pulmonary capacities in pre-and post-operative coronary artery bypass graft. Material and Methods: The study is a controlled clinical trial. The sample of this research was composed of 32 individuals admitted to the Imperial Hospital de Caridade (Florianópolis) undergoing elective coronary artery bypass grafting with cardiopulmonary bypass through a median thoracotomy (sternotomy). The study included individuals at high risk for developing pulmonary complications after surgery. The subjects were divided into control and intervention groups. The intervention group received inspiratory muscle training (IMT) with Threshold-loading device. The patients started breathing at a resistence equal of 30% of their maximal inspiratory mouth pressure. The patients trained 7 days a week, 2 times a day (3 sets, 10 repetitions) at least 2 weeks before surgery. Data collection was obtained by: individual assessments records, information about surgical procedures, spirometry, maximal mouth pressures, 6-minute walk test and pulmonary complications after surgery range. The data were analyzed using descriptive statistic and compared by specific statistical tests. Results: The demographic, clinical and surgical procedures were similar in both groups. In the assessment of lung volumes and flows was found that the FVC (p = 0.783), FEV1 (p = 0.668), PEF (p = 0.94) and FEV1/FVC (p =0.745) did not differ significantly between the intervention and control groups in different conditions before and after surgery, however, both showed a significant decrease after surgery. The maximal inspiratory pressure (MIP) differed significantly between groups (p <0.001). Before surgery, it was observed that there was a significant increase in MIP in the intervention group of 70.0 ± 19.7 cmH2O to 92.7 ± 26.8 cmH2O. In contrast, the control group showed a significant reduction in MIP from 75.9 ± 25.6 cmH2O to 66.6 ± 23.6 cmH2O. MIP in the intervention group had a better recovery, returning to baseline (57.5 ± 11.5 and 64.1 ± 14.1 cmH2O, respectively), but the control group remained decreased (43.4 ± 14.1 and 47.1 ± 15.0 cmH2O, respectively), after surgery. The MEP did not obtain significant difference between control and intervention group (p = 0.286), both groups showed a decrease after surgery. There was a significant increase in functional capacity in the intervention group (361.9 ± 92.6 to 434.4 ± 89.5) preoperatively, with smaller drop after surgery. The control group had a decrease in distance walked in 6 minutes (361.9 ±92.6 to 434.4 ±89.5m) in the preoperative period, not returning to baseline in the postoperative period. The length of stay in ICU (p = 0.564) and hospital stay (p = 0.892) did not differ between the two groups. The intervention group had a lower incidence of pulmonary complications (p = 0.046). Conclusion: An inspiratory muscle training program before surgery was able to increase the functional and pulmonary capacities in preoperative, and improve clinical outcomes in patients at high risk for developing pulmonary complications undergoing surgery coronary artery bypass graft. / Introdução: A realização da cirurgia de revascularização do miocárdio está associada com efeitos deletérios sobre a função pulmonar e capacidade funcional no pós-peratório imediato. Objetivo: Analisar os efeitos de um programa de treinamento muscular inspiratório (TMI) pré-operatório sobre a capacidade funcional e pulmonar pré e pós-operatória de cirurgia de Revascularização do Miocárdio (RM). Material e Métodos: O estudo caracteriza-se por ser um ensaio clínico controlado. A amostra desta pesquisa foi constituída por 32 indivíduos internados no Imperial Hospital de Caridade de Florianópolis que foram submetidos à cirurgia eletiva de revascularização do miocárdio com circulação extracorpórea através de toracotomia mediana (esternotomia). Foram incluídos no estudo, indivíduos de alto risco para o desenvolvimento de complicações pulmonares pós-operatórias. Os indivíduos foram alocados em grupo controle e intervenção. O grupo intervenção foi submetido a um treinamento muscular respiratório com auxílio do aparelho Threshold IMT. A carga utilizada para o fortalecimento respiratório foi de 30% do valor registrado na PIMáx. Os pacientes realizaram o treinamento 7 dias por semana, 2 vezes ao dia (3 séries de 10 repetições), pelo menos 2 semanas que antecedem a cirurgia. Foram utilizados como instrumentos de coleta de dados: fichas de avaliações do indivíduo, ficha de procedimentos cirúrgicos, espirometria, manovacuometria, teste de caminhada de 6 minutos e escala de complicações pulmonares pós-operatórias. Os dados foram analisados através da estatística descritiva e comparados por meio de testes estatísticos específicos. Resultados: Os dados demográficos, clínicos e cirúrgicos foram similares nos dois grupos. Na avaliação dos volumes e fluxos pulmonares foi verificado que a CVF (p=0.783), o VEF1 (p= 0.668), o PFE (p= 0.94) e o VEF1/CVF (p=0.745) não se diferenciaram significativamente entre os grupos controle e intervenção, nas diferentes condições pré e pós-operatórias, ambos apresentaram uma queda significativa após a cirurgia. A força muscular inspiratória diferenciou-se significativamente entre os grupos (p<0.001). No pré-operatório, observou-se que ocorreu um aumento significativo de força muscular inspiratória no grupo intervenção de 70.0 ±19.7cmH2O para 92.7 ±26.8 cmH2O. Em contrapartida, o grupo controle apresentou uma redução significativa da PImáx de 75.9 ±25.6 cmH2O para 66.6 ±23.6 cmH2O. A PIMáx do grupo intervenção teve uma melhor recuperação no pós-operatório, retornando ao valor basal (57.5 ±11.5 e 64.1 ±14.1 cmH2O, respectivamente), porém, a do grupo controle continuou diminuída (43.4 ±14.1 e 47.1 ±15.0 cmH2O, respectivamente), após a cirurgia. A PEMáx não obteve diferença significativa entre o grupo controle e intervenção (p=0.286), apresentando uma redução após a cirurgia. Houve um aumento significativo da capacidade funcional no grupo intervenção (361.9 ±92.6 para 434.4 ±89.5m) no pré-operatório, com menor queda após a cirurgia. O grupo controle teve uma diminuição da distância percorrida (384.8 ±136.3 para 333.7 ±116.3 m) no pré-operatório, não retornando aos valores basais, no pós-operatório. O tempo de internação em UTI (p=0.564) e permanência hospitalar (p=0.892) não apresentou diferença entre os dois grupos. O grupo intervenção teve menor incidência de complicações pulmonares (p=0.046). Conclusão: A realização de um programa de treinamento muscular inspiratório no pré-operatório foi capaz de incrementar a capacidade funcional e pulmonar pré-operatória, e melhorar os desfechos clínicos, em indivíduos com alto risco para o desenvolvimento de complicações pulmonares pós-operatórias submetidos à cirurgia de revascularização do miocárdio.

Cardiovascular diseases in the Czech Republic represent the main cause of death and significantly contribute to the sickness rate and premature disability. Possibilities of treatment of cardiovascular diseases keep developing increasingly these days. An important part is the follow up spa treatment as well as sufficiently performed effective cardio rehabilitation. The theoretical part characterizes functional examination of the lungs and stress tests in cardiology. Simultaneously it describes early spa treatment and defines quality of life. The aim of the diploma thesis, which deals with the vital capacity of the lungs, was to prove positive effect of early spa treatment on the vital capacity of the lungs and on improvement of quality of life, specifically with respect to positive perception of one´s overall physical health. Hypotheses - H1: An early spa therapy positively affects spirometry values. H2: Patients with an early spa therapy better perceive their overall physical health. A form of quantitative research was chosen, in order to verify the determined aims and hypotheses of the diploma thesis. A standardized international Short Form SF - 36 questionnaires on quality of life was used for the data collection. Spirometry was utilized for ascertaining objective functional parameters. Values of spirometry examination were used for comparison. 32 patients after cardiovascular surgery were included in the research, who were transferred to Lázně Poděbrady on the 6th - 8th day after the surgery, 22 of them being men (69%) and 10 women (31 %). The average age of patients under research was 66,06 + 11,48 years. The check group consisted of 10 healthy volunteers. 8 women (80 %) and 2 men (20 %) at the average age of 37,1 + 13,3 years were included in the research. It follows from the spirometry results measured before the heart surgery at IKEM cardio center that a difference in results between the second and third spirometry occurred. The second and third spirometrical examination is the period of time, when the respondent undergoes the early spa treatment. After the heart surgery spirometry values worsen and improve in the course of the spa therapy. The research showed that the perception of overall physical health after the heart surgery is subject to perception of pain, which negatively affected sense of overall perception of physical health. H1 was confirmed and H2 was not confirmed. In order to improve current situation, it would be suitable to devote not only to cardio rehabilitation but also to improvement of perception of pain, e.g. by means of psychotherapy (art therapy, music therapy?). It is also important to widen a possibility of outpatient cardio rehabilitation in each cardio center for patients after heart surgery.

Objetivo: Novas tendências na avaliação de risco trazem evidências de que modelos externos recalibrados ou remodelados funcionam melhor localmente. O objetivo deste estudo foi validar dois modelos externos e formular um modelo local, comparando-os na predição de mortalidade nos pacientes operados de coronária e/ou valva no InCor-HCFMUSP. Método: Entre 2007 e 2009, 3.000 pacientes foram sequencialmente operados de coronária e/ou valva no InCor-HCFMUSP. No banco de dados, foi realizada a validação dos modelos 2000 Bernstein-Parsonnet (2000BP) e EuroSCORE (ES), mediante testes de calibração e discriminação. O InsCor de 2.000 pacientes foi elaborado mediante a utilização de técnicas de bootstrap. Nos próximos 1.000 pacientes foi realizada a validação interna do modelo, e seu desempenho medido frente ao 2000BP e ES. Resultados: Houve uma diferença significativa na prevalência dos fatores de risco entre as populações do estudo, ES e 2000BP. Na validação externa dos modelos, o ES apresentou uma boa calibração (P=0,596); no entanto, o 2000BP revelou-se inadequado (P=0,047). Na discriminação, a área abaixo da curva ROC revelou-se boa para ambos os modelos, ES (0,79) e 2000BP (0,80). Utilizando a técnica de bootstrap, 10 variáveis: idade >70 anos, sexo feminino, cirurgia associada, infarto do miocárdio <90 dias, reoperação, cirurgia da valva aórtica, cirurgia da valva tricúspide, creatinina <2mg/dl, fração de ejeção <30% e estado pré-operátorio crítico (eventos), foram selecionadas para formulacão do InsCor. Na validação interna do InsCor, a calibração foi adequada, com P=0,184. Na discriminação, a área abaixo da curva ROC foi boa (0,79). Neste grupo, a área abaixo da curva ROC foi de 0,81 e 0,82 para o ES e 2000BP, respectivamente, mostrando-se apropriada para ambos os modelos. Conclusões: O InsCor e o ES tiveram melhor desempenho que o 2000BP em todas as fases da validação; pórem o novo modelo, além de se identificar com os fatores de risco locais, é mais simples e objetivo para a predição de mortalidade nos pacientes operados de coronária e/ou valva no InCor-HCFMUSP / Background: New trends in risk assessment bring evidence that recalibrated or remodeled external models work best locally. The aim of this study was to validate two external models and formulate a local model, comparing them to predict mortality in patients who underwent coronary bypass surgery and/or heart valve surgery at InCor-HCFMUSP. Method Between 2007 and 2009, 3.000 patients were sequentially operated to coronary bypass surgery and/or heart valve surgery at InCor-HCFMUSP. The database was assessment to validate the models 2000 Bernstein-Parsonnet (2000BP) and EuroSCORE (ES) through calibration and discrimination tests. The InsCor of 2,000 patients (2/3 of database) was elaborated using bootstrap techniques. Over the next 1000 patients (1/3 of database) the internal validation of the InsCor was performed and its performance compared against the 2000BP and ES. Results: Significant difference in the prevalence of risk factors was found among the external and study populations (P<0,001). In the external validation of these models, the ES showed good calibration (P = 0.596); however, 2000BP was inadequate (P = 0.047). In discrimination, the area under the ROC curve was good for both models, ES (0.79) and 2000BP (0.80). With the bootstrap technique, 10 variables: age> 70 years, female, CABG + valve surgery, myocardial infarction <90 days, reoperation, aortic valve surgery, tricuspid valve surgery, creatinine <2mg/dl, ejection fraction <30% and critical preoperative state (events) were chosen to formulate the InsCor. In the validation of InsCor, the calibration was appropriate with P = 0.184. In discrimination, the area under the ROC curve was good (0.79). In this group, the area under the ROC curve was 0.81 and 0.82 for ES and 2000BP, respectively, being suitable for both models. Conclusions: The InsCor and ES outperformed the 2000BP at all stages of validation, but the new model, besides identifying itself with the local risk factors, is more simple and objective for the prediction of mortality in patients who underwent coronary bypass surgery and/or heart valve surgery at InCor-HCFMUSP.

Duas técnicas invasivas para o tratamento da doença aterosclerótica coronariana oclusiva firmaram-se ao longo dos anos: revascularização cirúrgica do miocárdio e angioplastia transcutânea com stents metálicos. O estudo visa comparar as alterações histopatológicas causadas por stents metálicos coronarianos fabricados com a superliga de composição química em porcentagem em peso cromo 20%, tungstênio 15%, níquel 10% e cobalto restante, designada ASTM F.90, revestidos, ou não, com carbeto de silício pelo processo de asperção térmica originando uma superfície hidrofílica. Stents com espessura das hastes entre 80 a 90 nm, área das células entre 1,4 a 2,1 mm² e relação metal-artéria de 13 a 19%, em pacientes reestenosantes que sofreram posteriormente revascularização cirúrgica do miocárdio, com aqueles não submetidos à angioplastia prévia. Foram determinados dois grupos: grupo I ou grupo controle, pacientes que sofreram revascularização cirúrgica do miocárdio sem angioplastia prévia de qualquer natureza; grupo II pacientes submetidos à revascularização cirúrgica do miocárdio, após reestenose intra-stent coronariana. Pacientes de ambos os grupos foram avaliados rotineiramente quanto à indicação e risco cirúrgico e durante o procedimento convencional da revascularização cirúrgica do miocárdio utilizando circulação extracorpórea, antes de realizar a anastomose do enxerto vascular na coronária, amostras contendo pequenos fragmentos de endotélio foram retiradas juntamente com fragmentos dos stents, enviadas para análise histopatológica e produção de laminas coradas com H-E. Observou-se a presença de arterite crônica caracterizada por infiltrado mononuclear em conjunto com fenômeno de proliferação fibroblástica e de musculatura lisa naqueles pacientes que apresentavam reestenose intra-stent, sendo mais intenso no local do stent. A visualização das superfícies dos stents em escala nanometrica (MFA) é de suma importância para análise estrutural das próteses, avaliando irregularidades nas superfícies recobertas das hastes dos stents. A persistência de arterite crônica coronariana avaliada por infiltrado linfomononuclear e proliferação de fibrocolágeno foi constatada em pacientes reestenosantes. / Two invasive techniques for the treatment of occlusive coronary atherosclerosis disease were signed over the years: coronary artery bypass surgery and transcutaneous angioplasty with bare metal stent. The study attempts to compare the histopathological abnormality caused in patients with implantation of bare metal stent in coronary made with: Chromium 20%, Tungsten 15%, Nickel 10% and Cobalt remainder, ASTM F.90 alloy for surgical implant applications, and covered with a thin layer of amorphous silicon carbide, or not, and its total or partial obstruction, after undergoing coronary artery bypass grafting, with those who had coronary artery bypass surgery with no previous angioplasty. Two groups were studied: group I, or control group, patients who underwent coronary artery bypass grafting without previous angioplasty of any kind; group II of patients undergoing coronary artery bypass surgery after coronary-stent restenosis. Patients in both groups were evaluated for the indication and surgical risk; was done routinely during the procedure of conventional coronary artery bypass grafting with cardiopulmonary bypass. Before performing the anastomosis in coronary vascular graft, a small fragment of the endothelium was removed along whit a fragment of the stent, and sent for analysis with hematoxilin-eosin. The presence of chronic inflammatory coronary reaction was detected, mediated by mononuclear cells with phenomenon of fibroblast and smooth muscle proliferation in patients presenting in-stent restenosis. It w coronary reaction as also observed that the inflammatory and proliferative process is more intense at the site of stent implantation. The analysis of surface of the stents used atomic force microscopy proved to be an important method for the surface analysis for stents, and showed on nanometric scale an irregular coverage of silicon carbide. In conclusion, in the patients with restenosis in-stent occurs persistence of chronic inflammation with mononuclear cells and process of fibroblast proliferation.

Pacientes submetidos à revascularização do miocárdio (RM), frequentemente utilizam beta-bloqueadores no pré-operatório para o controle da angina pectoris, e continuam o tratamento após a cirurgia, para a redução de mortalidade e complicações cardiovasculares perioperatórias. Entretanto, a circulação extracorpórea (CEC), empregada na maioria das cirurgias cardíacas, pode alterar as concentrações plasmáticas e a disposição cinética de muitos fármacos, e consequentemente seus efeitos terapêuticos. O atenolol é um beta-bloqueador altamente hidrossolúvel, de absorção incompleta e eliminação renal-dependente. O objetivo deste estudo foi o de investigar a influência da CEC sobre as concentrações plasmáticas do atenolol no intra-operatório de cirurgia cardíaca, além de comparar a sua farmacocinética no pré e pós-operatório de RM com CEC, em pacientes com insuficiência coronariana. Investigou-se ainda, a variabilidade das concentrações plasmáticas do atenolol no período que antecede a cirurgia cardíaca. Na primeira etapa, avaliaram-se 19 pacientes coronarianos, em terapia crônica com atenolol PO, submetidos à cirurgia cardíaca com ou sem CEC. Na segunda parte, investigaram-se os períodos pré e pós-cirúrgico de 7 pacientes submetidos à RM com CEC e tratados com atenolol PO em regime de doses múltiplas. Todos os pacientes investigados apresentavam função renal dentro da normalidade ou leve disfunção renal, decorrente da idade e da insuficiência coronariana. O monitoramento do atenolol plasmático no intra-operatório de RM e o estudo farmacocinético realizado antes e após a revascularização, exigiram coletas de amostras sangüíneas seriadas. A quantificação do atenolol em plasma foi realizada através da cromatografia líquida de alta eficiência com detector de fluorescência e consistiu num procedimento analítico rápido, simples e de baixo custo. Apenas 200 L de plasma foram utilizados em cada análise cromatográfica. O estudo de validação demonstrou que o método desenvolvido apresenta alta linearidade, sensibilidade e seletividade adequadas, alta recuperação, boa precisão e exatidão, além de estabilidade e robustez. Conclui-se que a circulação extracorpórea altera as concentrações do atenolol no intra-operatório de RM, visto que o decaimento das concentrações plasmáticas mostrou-se mais pronunciado na ausência da CEC. Entretanto, apesar das maiores concentrações obtidas ao final da cirurgia com CEC, o atenolol mostra-se seguro, em virtude do baixo acúmulo do fármaco administrado em regime de doses múltiplas. Além disso, a disposição cinética do atenolol permaneceu inalterada, quando os períodos pré e pós-operatórios foram comparados; entretanto, registrou-se uma tendência à normalização do volume de distribuição e da depuração plasmática do atenolol após a revascularização. Adicionalmente, a ausência de correlação entre meia-vida biológica e volume aparente de distribuição sugere que, tanto no pré quanto no pós-operatório, as concentrações do atenolol dependem apenas da sua depuração plasmática. Finalmente, verificou-se que o atenolol apresenta baixa variabilidade inter-pacientes nos regimes posológicos empregados no tratamento da insuficiência coronariana. / Patients submitted to coronary artery bypass grafting (CABG) surgery frequently are using beta-blockers agents for the control of angina pectoris, and continue the treatment after the surgery to reduce the mortality and cardiovascular events. However, the technique of cardiopulmonary bypass (CPB), used in most cardiac surgeries with cardioplegia, causes important changes in the plasma concentrations and pharmacokinetics of many drugs and may also alter their therapeutic effects. Atenolol is a hydrophilic beta-blocker characterized by incomplete absorption, a relatively small volume of distribution and a renal function-dependent elimination. The objective of this study was to investigate the effects of CPB on the plasma concentrations of atenolol during the intra-operative period of cardiac surgery, as well as, to compare the pharmacokinetics of atenolol in the pre and post-operative periods of revascularization with CPB, in patients with coronary insufficiency. In addition, it was investigated the variability of plasma atenolol concentrations before the cardiac surgery. In the first part of the study, it was investigated 19 coronary patients, under chronic therapy with atenolol and submitted to cardiac surgery performed with and without CPB. At the second part, it was evaluated the pre and post-operative periods from 7 patients submitted to the CABG surgery with CPB, who were chronically treated with atenolol in a multiple regimen. All enrolled patients presented normal or slightly reduced renal function as a result of age and underlying disease. A serial blood samples collection was required for monitoring of plasma atenolol concentrations at the intra-operative period and also for pharmacokinetic study at the pre and post-CABG. The quantification of plasma atenolol was performed using high-performance liquid chromatography with fluorescence detection and consisted of a relatively rapid, simple and low-cost analytical procedure. Only 200 µL of plasma was used for each chromatographic analysis. Validation of this analytical method showed high linearity, adequate sensitivity and selectivity, high recovery, good accuracy and precision, in addition to stability and a guarantee of robustness. It was concluded that the CPB changes plasma atenolol concentrations in the intra-operative period, since a marked decrease in plasma atenolol concentrations was observed in patients undergoing cardiac surgery without CPB. Thus, despite the lower decline in plasma levels observed in patients submitted to CPB, atenolol can be used safely, due to the low accumulation of the drug administrated at multiple dose regimens. In addition, pharmacokinetics of atenolol remained unaltered when pre and post-operative periods were compared; although it was observed a tendency of normalization of volume of distribution and plasma clearance of atenolol after the revascularization. Moreover, the lack of correlation between biological half-life and apparent volume of distribution suggests that, in both periods, plasma atenolol concentration only depends on its plasma clearance. Finally, it was verified a small inter-patient variability of atenolol in the dose regimens used for the control of coronary insufficiency.

Durante a cirurgia de revascularização do miocárdio com circulação extracorpórea e hipotermia (CEC-H) ocorre alteração na efetividade do propofol e na sua farmacocinética realizada a partir das concentrações plasmáticas do propofol total no decurso do tempo. A ligação do propofol à proteína plasmática parece estar alterada em consequência de diversos fatores incluindo a hemodiluição e a heparinização que ocorre no início da circulação extracorpórea, uma vez que se reportou anteriormente que a concentração plasmática do propofol livre aumentou durante a realização da circulação extracorpórea normotérmica. Por outro lado, a infusão alvo controlada é recomendada para manter a concentração plasmática do propofol equivalente ao alvo de 2 &#181g/mL durante a intervenção cirúrgica com CEC-H. Se alterações significativas na hipnose do propofol ocorrem nesses pacientes, então o efeito aumentado desse agente hipnótico poderia estar relacionado à redução na extensão da ligação do fármaco as proteínas plasmáticas; entretanto, o assunto ainda permanece em discussão e necessita de investigações adicionais. Assim, o objetivo do estudo foi investigar as concentrações plasmáticas de propofol livre em pacientes durante a revascularização do miocárdio com e sem o procedimento de CEC-H através da abordagem PK-PD. Dezenove pacientes foram alocados e estratificados para realização de cirurgia de revascularização do miocárdio com circulação extracorpórea (CEC-H, n=10) ou sem circulação extracorpórea (NCEC, n=9). Os pacientes foram anestesiados com sufentanil e propofol alvo de 2 &#181g/mL. Realizou-se coleta seriada de sangue para estudo farmacocinético e o efeito foi monitorado através do índice bispectral (BIS) para medida da profundidade da hipnose no período desde a indução da anestesia até 12 horas após o término da infusão de propofol, em intervalos de tempo pré-determinados no protocolo de estudo. As concentrações plasmáticas foram determinadas através de método bioanalítico pela técnica de cromatografia líquida de alta eficiência. A farmacocinética foi investigada a partir da aplicação do modelo aberto de dois compartimentos, PK Solutions v. 2. A análise PK-PD foi realizada no Graph Pad Prisma v.5.0 após a escolha do modelo do efeito máximo (EMAX sigmóide, slope variável). Os dados foram analisados utilizando o Prisma v. 5.0, p<0,05, significância estatística. As concentrações plasmáticas de propofol total foram comparáveis nos dois grupos (CEC-H e NCEC); entretanto o grupo CEC-H evidenciou aumento na concentração do propofol livre de 2 a 5 vezes em função da redução na ligação do fármaco às proteínas plasmáticas. A farmacocinética do propofol livre mostrou diferença significativa entre os grupos no processo de distribuição pelo prolongamento da meia vida e aumento do volume aparente, e no processo de eliminação em função do aumento na depuração plasmática e redução na meia vida biológica no grupo CEC-H. A escolha do modelo EMAX sigmóide, slope variável foi adequada uma vez que se evidenciou alta correlação entre os valores do índice bispectral e as concentrações plasmáticas do propofol livre (r2>0.90, P<0.001) para os pacientes investigados. / During coronary artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB) profound changes occur on propofol effect and on kinetic disposition related to total drug plasma measurements in these patients. It was reported that drug plasma binding could be altered as a consequence of hemodilution and heparinization before starts CPB since free propofol plasma levels was increased by twice under normothermic procedure. In addition, the target controlled infusion (TCI) is recommended to maintain propofol plasma concentration (2 &#181g/mL) during CABG CPB-H intervention. However, whether significant changes that occur in propofol hypnosis in these patients could be related to the reduction on the extension of drug plasma binding remain unclear and under discussion until now. Then, the objective of this study was to investigate propofol free plasma levels in patients undergoing CABG with and without CPB by a pharmacokinetics-pharmacodynamics (PK-PD) approach. Nineteen patients were scheduled for on-pump coronary artery bypass grafting (CABG-CPB, n=10) or off-pump coronary artery bypass grafting (OPCABG, n=9) were anesthetized with sufentanil and propofol TCI (2 &#181g/mL). Blood samples were collected for drug plasma measurements and BIS were applied to access the depth of hypnosis from the induction of anesthesia up to 12 hours after the end of propofol infusion, at predetermined intervals. Plasma drug concentrations were measured using high-performance liquid chromatography, followed by a propofol pharmacokinetic analysis based on two compartment open model, PK Solutions v.2; PK-PD analysis was performed by applying EMAX model, sigmoid shape-variable slope and data were analyzed using Prisma v. 5.0, considering p<0.05 as significant difference between groups. The total propofol plasma concentrations were comparable in both groups during CABG; however it was shown in CPB-group significant increases in propofol free plasma concentration by twice to fivefold occur as a consequence of drug plasma protein binding reduced in these patients. Pharmacokinetics of free propofol in CPB-H group compared to OPCAB group based on two compartment open model was significantly different by the prolongation of distribution half-life, increases on plasma clearance, and biological half-life shortened. In addition, the kinetic disposition of propofol changes in a different manner considering free drug levels in the CPB-H group against OPCAB group as follows: prolongation of distribution half-life and increases on volume of distribution, remaining unchanged biological half-life in spite of plasma clearance increased. BIS values showed a strong correlation with free drug levels (r2>0.90, P<0.001) in CPB-H group and also in OPCAB group by the chosen EMAX model sigmoid shape-variable slope analyzed by GraphPad Prisma v.5.0.