Die chirurgische Mitralklappenrekonstruktion (MKR) ist der konservativen Therapie bei signifikanter Mitralklappeninsuffizienz (MI) überlegen. Bisher fehlen sensitive präoperative Parameter zur Detektion latenter linksventrikulärer Funktionsstörungen. Aufgrund der pathophysiologisch bedingten Nachlastreduktion und Vorlaststeigerung bei MI bergen die konventionell verwendeten Ejektionsindices, Ejektionsfraktion (EF) und Fractional Area Change (FAC), die Gefahr der Überschätzung der effektiven Pumpfunktion des linken Ventrikels (LV). Der dopplersonographisch erhobene Tei Index gilt als ein Marker globaler myokardialer Funktion. Ziel der vorliegenden Studie war es, mit dem Tei Index (bzw. dem Myokardialen Performance Index, MPI) einen sensitiveren präoperativen Parameter zur Prädiktion der postoperativen linksventrikulären Funktion zu finden. Hierzu wurden im Rahmen einer prospektiven klinischen Studie 130 Patienten mit signifikanter MI am Herzzentrum Leipzig entsprechend den ASE/SCA Leitlinien vor und nach kardiopulmonaler Bypass-Operation mittels transösophagealer echokardiographischer (TEE) Bildgebung untersucht. Die Quantifizierung der MI erfolgte durch Messung der Vena contracta (VC). Die FAC wurde in der transgastrischen midpapillären kurzen Achse und die EF im midösophagealen Zwei- sowie Vier-Kammer-Blick erfasst. Die Zeitintervalle zur Berechnung des Tei Index wurden im tiefen transgastrischen und midösophagealen Vier-Kammer-Blick erfasst. Eine statistische Korrelation zwischen präoperativen Tei Index und postoperativer EF und FAC konnte zur Validierung unserer Hypothese nicht detektiert werden. Folgend kann der Tei Index nicht als Prädiktor der effektiven linksventrikulären Funktion vor MKR gewertet werden.

Die vorliegende Arbeit beschreibt die Rolle der intraoperativen transösophagealen Echokardiografie während herzchirurgischer Eingriffe mit Schwerpunkt Mitralklappenrekonstruktion. Ziel ist die Beschreibung der Aufgaben und Möglichkeiten dieses Verfahrens im klinischen Alltag und das Aufzeigen möglicher neuer Einsatzgebiete, wie die bildgestützte Größenbestimmung der Annuloplastieringe. Die intraoperative Echokardiografie hat sich seit den Anfängen in den achtziger Jahren des letzten Jahrhunderts zu einem Standardverfahren während herzchirurgischer Eingriffe entwickelt. Sie dient zum einen zur kardialen Diagnostik und zum anderen als Monitorverfahren. Trotz in der Regel gut vordiagnostizierter Patienten führt die intraoperativ durchgeführte transösophageale Echokardiografie während herzchirurgischer Eingriffe nicht selten zur Diagnose vorher nicht bekannter Pathologien und somit zu einer Änderung im chirurgischen Vorgehen. Speziell während der Mitralklappenrekonstruktion ermöglicht diese Methode die Diagnostik und Lokalisation der pathologischen Segmente, die Bestätigung des Schweregrades und dem Erkennen möglicher Risikofaktoren. Hierfür ist jedoch eine umfassende, standardisierte Untersuchung notwendig. Der Einsatz moderner Operationstechniken, wie z.B. der kathetergestützten Implantation der Aortenklappe ohne Einsatz der Herz-Lungen-Maschine, ohne Eröffnung des Sternums, macht eine direkte visuelle Einschätzung der Herzfunktion unmöglich. Sowohl zur Evaluierung der Herzfunktion als auch zur Größenbestimmung der zu implantierenden Klappenprothesen ist ein bildgebendes Verfahren unabdingbar. Die dreidimensionale transösophageale Echokardiografie ermöglicht nun in Echtzeit die komplette Darstellung z.B. der Mitralklappe. Dies erleichtert nicht nur die Verständigung zwischen Echokardiographeur und Chirurgen bei der Darstellung der Befunde, sondern ermöglicht nun erstmals auch die bildgestützte Planung des operativen Vorgehens, wie, z.B. die Visualisierung und Größenbestimmung der zu implantierenden Annuloplastieringe, die als Computermodelle auf die dreidimensionale Darstellung der Mitralklappe projiziert werden können. In der postoperativen TEE-Untersuchung ist die Evaluierung des rekonstruierten Mitralklappenapparates, die Quantifizierung einer eventuell bestehenden residualen Mitralinsuffizienz, sowie deren genaue Lokalisation primäres Ziel. Weiterhin sollten iatrogen aufgetretene Komplikationen in einer umfassenden postoperativen TEE-Untersuchung diagnostiziert werden wie z.B. der Verschluss des Ramus circumflexus, Aortendissektion, etc. Zusammenfassend wird in dieser Habilitationsarbeit die Rolle der intraoperativen Echokardiografie bei herzchirurgischen Eingriffen dargestellt. Ein besonderer Schwerpunkt in dieser Arbeit ist die transösophageale Echokardiographie bei Mitralklappenoperationen im Hinblick auf die Darstellung der bestehenden Pathologie, der Quantifizierung der Mitralinsuffizienz und dem Erkennen bestehender Risikofaktoren präoperativ bzw das Erkennen der Komplikation postoperativ.:1. Einführung in die Thematik 5 1.1. Einführung 5 1.2. Grundlage der vorliegenden Habilitationsarbeit 5 1.3. Intraoperative Echokardiografie in der Kardioanästhesie 5 1.4. Intraoperative Echokardiografie bei chirurgischer Mitralklappenrekonstruktion 8 1.5 .Die dreidimensionale transösophageale Echokardiographie zur bildgestützten Größenbestimmung des Annuloplastieringes während Mitralklappenrekonstruktion 9 2. Habilitationsschrift 11 2.1. Geschichte der Echokardiographie 11 2.2. Geschichte der Entwicklung der transösophagealen Echokardiographie 11 2.3. Einsatz der intraoperativen transösophagealen Echokardographie 12 2.3.1 Eigene Arbeit im Original: 13 2.3.2. Eigene Arbeit im Original 13 2.3.4. Echokardiographische Kontrolle von mechanischen Unterstützungssystemen 14 2.3.5. Transösophageale Echokardiografie bei kathetergestützter Aortenklappen- Implantation 15 2.3.5.1. Eigene Arbeit im Original: 16 2.3.5.2. Eigene Arbeit im Original: 16 2.3.6. Einfluss der intraoperativen Echokardiografie bei herzchirurgischen Eingriffen. 17 2.3.6.1. Eigene Arbeit im Original: 17 2.3.6.2. Eigene Arbeit im Original: 18 2.4. Intraoperative Echokardiographie bei Mitralklappenrekonstruktion 20 2.4.1. Einführung 20 2.4.2. Aufgabe der intraoperativen Echokardiographie bei Mitralklappenrekonstruktion 20 2.4.2.1. Beurteilung der Morphologie und Funktion des Mitralklappenapparates 21 2.4.2.1. Eigene Arbeit im Original: 30 2.4.2.2. Erkennen der Ursachen der Mitralinsuffizienz 31 2.4.2.2.1. Eigene Arbeit im Original: 34 2.4.2.2.2 Eigene Arbeit im Original: 35 2.4.2.3. Bestimmung des Schweregrades der Mitralinsuffizienz mittels intraoperativer Echokardiografie 36 2.4.2.4. Beurteilung der systolischen Funktion bei vorhandener Mitralinsuffizienz 38 2.4.2.4.1. Hilfestellung bei der chirurgischen Planung 39 2.4.2.4.2. Eigene Arbeit im Original: 39 2.4.2.4.3. Eigene Arbeit im Original: 40 2.4.2.4.4 Eigene Arbeit im Original: 41 2.4.3. Die dreidimensionale transösophageale Echokardiographie zur bildgestützten Größenbestimmung des Annuloplastieringes während Mitralklappenrekonstruktion 42 2.4.3.1. Eigene Arbeit im Original: 43 2.4.3.2. Eigene Arbeit im Original: 44 2.4.4. Postoperative TEE- Untersuchung 45 2.4.4.1. Darstellung des Ramus circumflexus 45 2.4.4.2. Kontrolle der Entlüftung des Herzens 45 2.4.4.3. Detektion einer residualen Mitralinsuffizienz 45 2.4.4.4 Ausschluss einer Mitralstenose 46 3. Erklärung über die eigenständige Anfertigung der Habilitationsschrift 62 Lebenslauf 63 Danksagung 65

Unicuspid aortic valve (UAV), which is a rare congenital anomaly, usually presents as aortic stenosis and/or aortic regurgitation. Here we present a case of UAV co-existent with an ascending aortic aneurysm. A 26-year-old male with no significant past medical history presented to the hospital after two episodes of syncope. Transthoracic echocardiogram showed an ejection fraction of 62%, severely stenotic aortic valve, and moderate aortic regurgitation. Computed tomography revealed calcification of the aortic valve, compatible with aortic stenosis and aneurysm of the ascending aorta measuring 4.3 cm in diameter. He underwent successful aortic valve replacement and repair of ascending aortic aneurysm. He recovered well without any complications. This case suggests that any young patient who presents with syncope, aortic stenosis would be a differential and further workup by any available non-invasive modality needs to be performed.

INTRODUÇÂO: Durante o desenvolvimento da hipertensão arterial sistêmica (HAS) ocorre a hiperatividade simpática, que está relacionada ao comprometimento dos sistemas baro e quimiorreflexo arteriais e disfunção ventricular esquerda (VE). Entretanto, a função ventricular direita (VD) tem sido pouco avaliada no contexto da HAS associada à desnervação sino-aórtica (DSA). OBJETIVO: Avaliar a função biventricular de forma não-invasiva e invasiva, a capacidade funcional, a sensibilidade barorreflexa e o controle autonômico cardiovascular em ratos Wistar (W) e ratos espontaneamente hipertensos (SHR) submetidos ou não à DSA. MÉTODOS: Após 10 semanas de DSA, a função cardíaca foi avaliada pelo teste de esforço (TE), ecocardiograma transtorácico e transesofágico, e a pressão diastólica final biventricular; as funções hemodinâmica e autonômica foram avaliadas pelo registro da pressão arterial (PA) e da freqüência cardíaca (FC), variabilidade da PA e da FC e sensibilidade barorreflexa. Os ratos (n = 32) foram divididos em 4 grupos: 16 W com (n = 8) e sem DSA (n = 8), 16 SHR com (n = 8) ou sem DSA (n = 8). RESULTADOS: A PA e a FC não apresentaram alterações entre os grupos DSA e não-DSA, entretanto, os SHR apresentaram níveis mais elevados da PA comparado com W. O TE mostrou que os SHR apresentaram melhor capacidade funcional em relação ao DSA e SHRDSA (W: 1,16±0,3m/s, DSA: 0,9±0,15m/s, *SHR: 1,46±0,29m/s, SHR-DSA: 1,02±0,31, *p< 0,05 vs. DSA e SHRDSA). Os SHRs apresentaram aumento da variabilidade da PA comparados aos W. Após a DSA houve aumento da variabilidade PA em todos os grupos comparados ao W (W: 15±29 mmHg2, *DSA: 49±27 mmHg2, *SHR: 60±29 mmHg2, *SHR-DSA: 137±76 mmHg2, *p<0,05 vs. W). Foi observado hipertrofia concêntrica do VE; disfunção sistólica segmentar e diastólica global do VE; disfunção sistólica global e segmentar, e diastólica global do VD; sinais indiretos de hipertensão arterial pulmonar pela ecocardiografia, mas evidentes no grupo SHRDSA. A pressão diastólica final do VD mostrou aumento em todos os grupos comparados com W (W: 3±0.39mmHg, *DSA:4,7±0,52mmHg, *SHR: 6;6±1.1mmHg, *SHRDSA: 7,8±0.87mmHg, *p< 0,05 vs. W), enquanto a pressão diastólica final do VE mostrou aumento dos grupos SHR e SHRDSA em relação ao W, e dos SHRDSA em relação aos DSA (W: 5,83±0,19 mmHg, DSA: 8,98±1,2 mmHg, *SHR: 12,51±4,73 mmHg, *#SHRDSA: 14,57±2.52 mmHg, *p< 0,05 vs. W, #p< 0,05 vs. DSA). Houve relação entre medidas não- invasivas e invasivas do VD, mostrando uma boa acurácia das medidas ecocardiográficas. CONCLUSÕES: Nossos resultados sugerem que a disfunção baroreflexa compromete a função biventricular. Além disso, os achados observados nos índices ecocardiográficos do VD indicam que a DAS pode induzir a elevação da pressão arterial pulmonar, reforçando o papel da disfunção barorreflexa na patogênese da doença cardíaca hipertensiva / INTRODUCTION: During the development of hypertension, sympathetic hyperactivity commonly seems to be related to the left ventricular (LV) dysfunction and baro and chemoreflexes impairment. However, right ventricle (RV) function has not been evaluated specially regarding the association of hypertension and baroreflex dysfunction. OBJECTIVE: To evaluate noninvasively and invasively the biventricular myocardial function, the functional capacity, the baroreflex sensitivity and the cardiovascular autonomic control in Wistar (W) rats and spontaneously hypertensive rats (SHR) submitted or not to sinoaortic denervation (SAD). METHODS: Ten weeks after DSA, cardiac function was evaluated by the maximal exercise test (MET), by transthoracic (TT) and transesophageal echocardiography (TEE) and the biventricular end diastolic pressures (EDP). Additionally, hemodynamic and autonomic functions were evaluated by the blood pressure (BP) and heart rate (HR) records, BP and HR variability and baroreflex sensitivity. The rats (n=32) were divided in 4 groups: 16 Wistar (W) with (n=8) or without SAD (n=8) and 16 SHR, with (n=8) or without SAD (n=8). RESULTS: Blood pressure and HR did not show any change between the groups SAD and without SAD, although, SHR showed higher BP levels in comparison to W. MET results showed that SHR had better functional capacity compared to SAD and SHRSAD (W: 1,16±0,3m/s, DSA: 0,9±0,15m/s, *SHR: 1,46±0,29m/s, SHR-DSA: 1,02±0,31, *p< 0.05 vs. SAD and SHRSAD). BP variability was increased in SHR groups compared to W. After SAD, BP variability increased in all groups compared to W (W: 15±29 mmHg2, *DSA: 49±27 mmHg2, *SHR: 60±29 mmHg2, *SHR-DSA: 137±76 mmHg2, *p<0.05 vs. W). Left ventricular concentric hypertrophy; segmental systolic dysfunction and global diastolic LV dysfunction; segmental and global systolic dysfunction, and global diastolic RV dysfunction; indirect signals of pulmonary arterial hypertension were shown by echocardiography, mostly evident in SHRSAD. The RV-EDP increased in all groups compared to W (W: 3±0.39mmHg, *SAD:4.7±0.52mmHg, *SHR: 6.6±1.1mmHg, *SHRSAD: 7.8±0.87mmHg, *p<0.05 vs. W), and the LV-EDP increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD (W: 5,83±0,19 mmHg, SAD: 8.98±1.2 mmHg, *SHR: 12.51±4.73 mmHg, *#SHRSAD: 14.57±2.52 mmHg, *p<0.05 vs. W, #p<0.05 vs. DSA). There was a relation between invasive or noninvasive measurements of the RV showing good accuracy of echocardiographic measurements. CONCLUSIONS: Our results suggest that baroreflex dysfunction impaired biventricular function. Moreover, the findings of RV echocardiographic indices indicate that SAD may lead to increased pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of the hypertensive cardiac disease

Chaque année, environ 1 à 1,25 million d’individus subiront une chirurgie cardiaque. [1] Environ 36 000 chirurgies cardiaques sont effectuées au Canada et 8000 procédures au Québec (http://www.ccs.ca). Le vieillissement de la population aura pour conséquence que la chirurgie cardiaque sera offerte à des patients de plus en plus à risque de complications, principalement en raison d’une co-morbidité plus importante, d’un risque de maladie coronarienne plus élevée, [2] d’une réserve physiologique réduite et par conséquent un risque plus élevé de mortalité à la suite d’une chirurgie cardiaque. L’une des complications significatives à la suite d’une chirurgie cardiaque est le sevrage difficile de la circulation extracorporelle. Ce dernier inclut la période au début du sevrage de la circulation extracorporelle et s’étend jusqu’au départ du patient de la salle d’opération. Lorsque le sevrage de la circulation extracorporelle est associé à une défaillance ventriculaire droite, la mortalité sera de 44 % à 86 %. [3-7] Par conséquent le diagnostic, l’identification des facteurs de risque, la compréhension du mécanisme, la prévention et le traitement du sevrage difficile de la circulation extracorporelle seront d’une importance majeure dans la sélection et la prise en charge des patients devant subir une chirurgie cardiaque. Les hypothèses de cette thèse sont les suivantes : 1) le sevrage difficile de la circulation extracorporelle est un facteur indépendant de mortalité et de morbidité, 2) le mécanisme du sevrage difficile de la circulation extracorporelle peut être approché d’une façon systématique, 3) la milrinone administrée par inhalation représente une alternative préventive et thérapeutique chez le patient à risque d’un sevrage difficile de la circulation extracorporelle après la chirurgie cardiaque. / Every year, 1 million to 1.25 million patients worldwide undergo cardiac surgery. [1] Up to 36,000 cardiac surgeries are performed each year in Canada and close to 8000 in Quebec (http://www.ccs.ca). Because of the aging of the population, cardiac surgery will increasingly be offered to patients at a higher risk of complications. Indeed, elderly patients have increased co-morbidities, and aging is also a significant risk factor in the prevalence of coronary artery disease. [2] The consequence is a reduced physiologic reserve, hence an increased risk of mortality. These issues will have a significant impact on future healthcare costs, because our population undergoing cardiac surgery will be older and more likely to develop postoperative complications. One of the most dreaded complications in cardiac surgery is difficult separation from cardiopulmonary bypass (CPB). The definition of difficult separation from CPB includes the time period from when CPB is initiated and until the patient leaves the operating room. When separation from CPB is associated with right ventricular failure, the mortality rate will range from 44% to 86%. [3-7] Therefore the diagnosis, the preoperative prediction, the mechanism, prevention and treatment of difficult separation from CPB will be crucial in order to improve the selection and care of patients and to prevent complications for this high-risk patient population. The hypotheses of this thesis are the following: 1) difficult separation from CPB is an independent factor of morbidity and mortality, 2) the mechanism of difficult separation from CPB can be understood through a systematic approach, 3) inhaled milrinone is a preventive and therapeutic approach in the patient at risk for difficult weaning from CPB after cardiac surgery.

INTRODUÇÂO: Durante o desenvolvimento da hipertensão arterial sistêmica (HAS) ocorre a hiperatividade simpática, que está relacionada ao comprometimento dos sistemas baro e quimiorreflexo arteriais e disfunção ventricular esquerda (VE). Entretanto, a função ventricular direita (VD) tem sido pouco avaliada no contexto da HAS associada à desnervação sino-aórtica (DSA). OBJETIVO: Avaliar a função biventricular de forma não-invasiva e invasiva, a capacidade funcional, a sensibilidade barorreflexa e o controle autonômico cardiovascular em ratos Wistar (W) e ratos espontaneamente hipertensos (SHR) submetidos ou não à DSA. MÉTODOS: Após 10 semanas de DSA, a função cardíaca foi avaliada pelo teste de esforço (TE), ecocardiograma transtorácico e transesofágico, e a pressão diastólica final biventricular; as funções hemodinâmica e autonômica foram avaliadas pelo registro da pressão arterial (PA) e da freqüência cardíaca (FC), variabilidade da PA e da FC e sensibilidade barorreflexa. Os ratos (n = 32) foram divididos em 4 grupos: 16 W com (n = 8) e sem DSA (n = 8), 16 SHR com (n = 8) ou sem DSA (n = 8). RESULTADOS: A PA e a FC não apresentaram alterações entre os grupos DSA e não-DSA, entretanto, os SHR apresentaram níveis mais elevados da PA comparado com W. O TE mostrou que os SHR apresentaram melhor capacidade funcional em relação ao DSA e SHRDSA (W: 1,16±0,3m/s, DSA: 0,9±0,15m/s, *SHR: 1,46±0,29m/s, SHR-DSA: 1,02±0,31, *p< 0,05 vs. DSA e SHRDSA). Os SHRs apresentaram aumento da variabilidade da PA comparados aos W. Após a DSA houve aumento da variabilidade PA em todos os grupos comparados ao W (W: 15±29 mmHg2, *DSA: 49±27 mmHg2, *SHR: 60±29 mmHg2, *SHR-DSA: 137±76 mmHg2, *p<0,05 vs. W). Foi observado hipertrofia concêntrica do VE; disfunção sistólica segmentar e diastólica global do VE; disfunção sistólica global e segmentar, e diastólica global do VD; sinais indiretos de hipertensão arterial pulmonar pela ecocardiografia, mas evidentes no grupo SHRDSA. A pressão diastólica final do VD mostrou aumento em todos os grupos comparados com W (W: 3±0.39mmHg, *DSA:4,7±0,52mmHg, *SHR: 6;6±1.1mmHg, *SHRDSA: 7,8±0.87mmHg, *p< 0,05 vs. W), enquanto a pressão diastólica final do VE mostrou aumento dos grupos SHR e SHRDSA em relação ao W, e dos SHRDSA em relação aos DSA (W: 5,83±0,19 mmHg, DSA: 8,98±1,2 mmHg, *SHR: 12,51±4,73 mmHg, *#SHRDSA: 14,57±2.52 mmHg, *p< 0,05 vs. W, #p< 0,05 vs. DSA). Houve relação entre medidas não- invasivas e invasivas do VD, mostrando uma boa acurácia das medidas ecocardiográficas. CONCLUSÕES: Nossos resultados sugerem que a disfunção baroreflexa compromete a função biventricular. Além disso, os achados observados nos índices ecocardiográficos do VD indicam que a DAS pode induzir a elevação da pressão arterial pulmonar, reforçando o papel da disfunção barorreflexa na patogênese da doença cardíaca hipertensiva / INTRODUCTION: During the development of hypertension, sympathetic hyperactivity commonly seems to be related to the left ventricular (LV) dysfunction and baro and chemoreflexes impairment. However, right ventricle (RV) function has not been evaluated specially regarding the association of hypertension and baroreflex dysfunction. OBJECTIVE: To evaluate noninvasively and invasively the biventricular myocardial function, the functional capacity, the baroreflex sensitivity and the cardiovascular autonomic control in Wistar (W) rats and spontaneously hypertensive rats (SHR) submitted or not to sinoaortic denervation (SAD). METHODS: Ten weeks after DSA, cardiac function was evaluated by the maximal exercise test (MET), by transthoracic (TT) and transesophageal echocardiography (TEE) and the biventricular end diastolic pressures (EDP). Additionally, hemodynamic and autonomic functions were evaluated by the blood pressure (BP) and heart rate (HR) records, BP and HR variability and baroreflex sensitivity. The rats (n=32) were divided in 4 groups: 16 Wistar (W) with (n=8) or without SAD (n=8) and 16 SHR, with (n=8) or without SAD (n=8). RESULTS: Blood pressure and HR did not show any change between the groups SAD and without SAD, although, SHR showed higher BP levels in comparison to W. MET results showed that SHR had better functional capacity compared to SAD and SHRSAD (W: 1,16±0,3m/s, DSA: 0,9±0,15m/s, *SHR: 1,46±0,29m/s, SHR-DSA: 1,02±0,31, *p< 0.05 vs. SAD and SHRSAD). BP variability was increased in SHR groups compared to W. After SAD, BP variability increased in all groups compared to W (W: 15±29 mmHg2, *DSA: 49±27 mmHg2, *SHR: 60±29 mmHg2, *SHR-DSA: 137±76 mmHg2, *p<0.05 vs. W). Left ventricular concentric hypertrophy; segmental systolic dysfunction and global diastolic LV dysfunction; segmental and global systolic dysfunction, and global diastolic RV dysfunction; indirect signals of pulmonary arterial hypertension were shown by echocardiography, mostly evident in SHRSAD. The RV-EDP increased in all groups compared to W (W: 3±0.39mmHg, *SAD:4.7±0.52mmHg, *SHR: 6.6±1.1mmHg, *SHRSAD: 7.8±0.87mmHg, *p<0.05 vs. W), and the LV-EDP increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD (W: 5,83±0,19 mmHg, SAD: 8.98±1.2 mmHg, *SHR: 12.51±4.73 mmHg, *#SHRSAD: 14.57±2.52 mmHg, *p<0.05 vs. W, #p<0.05 vs. DSA). There was a relation between invasive or noninvasive measurements of the RV showing good accuracy of echocardiographic measurements. CONCLUSIONS: Our results suggest that baroreflex dysfunction impaired biventricular function. Moreover, the findings of RV echocardiographic indices indicate that SAD may lead to increased pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of the hypertensive cardiac disease

We present a case of a previously asymptomatic 63-year-old woman who presented with worsening dyspnoea for 3 weeks. Initial transthoracic and later transoesophageal echocardiography confirmed biventricular non-compaction cardiomyopathy and a large secundum atrial septal defect (ASD) measuring 1.4 cm. Additionally, there was a haemodynamically significant left to right shunt causing acute decompensated systolic heart failure. She eventually underwent closure of the septal defect using a AMPLATZER Septal Occluder device. Decision to close the defect was made as the left to right shunt was causing severe pulmonary hypertension and acute heart failure. Since most heart failure treatments involve lowering of the LV afterload there was consideration that this could cause right to left shunting and could cause an Eisenmenger physiology. Hence the AMPLATZER Septal Occluder device was placed to eliminate the shunt through the ASD. The ASD combined with the non-compaction posed significant treatment challenge in this case.

Chaque année, environ 1 à 1,25 million d’individus subiront une chirurgie cardiaque. [1] Environ 36 000 chirurgies cardiaques sont effectuées au Canada et 8000 procédures au Québec (http://www.ccs.ca). Le vieillissement de la population aura pour conséquence que la chirurgie cardiaque sera offerte à des patients de plus en plus à risque de complications, principalement en raison d’une co-morbidité plus importante, d’un risque de maladie coronarienne plus élevée, [2] d’une réserve physiologique réduite et par conséquent un risque plus élevé de mortalité à la suite d’une chirurgie cardiaque. L’une des complications significatives à la suite d’une chirurgie cardiaque est le sevrage difficile de la circulation extracorporelle. Ce dernier inclut la période au début du sevrage de la circulation extracorporelle et s’étend jusqu’au départ du patient de la salle d’opération. Lorsque le sevrage de la circulation extracorporelle est associé à une défaillance ventriculaire droite, la mortalité sera de 44 % à 86 %. [3-7] Par conséquent le diagnostic, l’identification des facteurs de risque, la compréhension du mécanisme, la prévention et le traitement du sevrage difficile de la circulation extracorporelle seront d’une importance majeure dans la sélection et la prise en charge des patients devant subir une chirurgie cardiaque. Les hypothèses de cette thèse sont les suivantes : 1) le sevrage difficile de la circulation extracorporelle est un facteur indépendant de mortalité et de morbidité, 2) le mécanisme du sevrage difficile de la circulation extracorporelle peut être approché d’une façon systématique, 3) la milrinone administrée par inhalation représente une alternative préventive et thérapeutique chez le patient à risque d’un sevrage difficile de la circulation extracorporelle après la chirurgie cardiaque. / Every year, 1 million to 1.25 million patients worldwide undergo cardiac surgery. [1] Up to 36,000 cardiac surgeries are performed each year in Canada and close to 8000 in Quebec (http://www.ccs.ca). Because of the aging of the population, cardiac surgery will increasingly be offered to patients at a higher risk of complications. Indeed, elderly patients have increased co-morbidities, and aging is also a significant risk factor in the prevalence of coronary artery disease. [2] The consequence is a reduced physiologic reserve, hence an increased risk of mortality. These issues will have a significant impact on future healthcare costs, because our population undergoing cardiac surgery will be older and more likely to develop postoperative complications. One of the most dreaded complications in cardiac surgery is difficult separation from cardiopulmonary bypass (CPB). The definition of difficult separation from CPB includes the time period from when CPB is initiated and until the patient leaves the operating room. When separation from CPB is associated with right ventricular failure, the mortality rate will range from 44% to 86%. [3-7] Therefore the diagnosis, the preoperative prediction, the mechanism, prevention and treatment of difficult separation from CPB will be crucial in order to improve the selection and care of patients and to prevent complications for this high-risk patient population. The hypotheses of this thesis are the following: 1) difficult separation from CPB is an independent factor of morbidity and mortality, 2) the mechanism of difficult separation from CPB can be understood through a systematic approach, 3) inhaled milrinone is a preventive and therapeutic approach in the patient at risk for difficult weaning from CPB after cardiac surgery.

INTRODUÇÃO: Colapso alveolar é achado freqüente em lesão pulmonar aguda (LPA), levando ao aumento do shunt intrapulmonar e hipoxemia. Estratégias de tratamento atuais visam o recrutamento alveolar para melhora das trocas gasosas. Embora as manobras de recrutamento alveolar (MRA) sejam objetos de investigação nas últimas duas décadas, seu uso tem se tornado mais freqüente para o tratamento de pacientes com LPA. Volumes pulmonares e pressões pleurais elevados associados a MRA podem afetar a resistência vascular pulmonar e o trabalho cardíaco negativamente. Porém, o benefício da MRA na oxigenação, perante seus efeitos hemodinâmicos negativos, permanecem incertos devido à falta de informações dos efeitos cardiovasculares das MRAs. O objetivo deste estudo foi verificar, em modelo de LPA, os efeitos de um tipo de MRA- insuflação sustentada- associada a diferentes valores de PEEP no sistema cardiovascular durante um determinado período de observação. TIPO DE ESTUDO: estudo experimental prospectivo, controlado e randomizado. LOCAL: Laboratório de Anestesiologia Experimental- LIM 08. MATERIAL: Trinta e dois animais suínos. MÉTODO: Os animais anestesiados foram ventilados em modo volume-controlado e randomizados em quatro grupos (G1-PEEP; G2-PEEP-MRA; G3-LPA-PEEP; G4-LPA-PEEP-MRA) com oito animais cada. Os valores de PEEP foram progressivamente aumentados e diminuídos (5, 10, 15 e 20 cmH2O) em todos os animais e eram mantidos inalterados por 20 minutos em cada valor. Três insuflações sustentadas (MRA) de 30 cmH2O com duração de 20 segundos cada foram aplicadas em cada valor de PEEP nos grupos G2-PEEP-MRA e G4-LPA-PEEP-MRA. Para indução da LPA, principalmente em regiões pulmonares dependentes, o ácido clorídrico (0.05N, 4mL/kg) foi instilado na traquéia por meio de broncofibroscópio nos grupos G3-LPA-PEEP e G4-LPA-PEEP-MRA. Ecocardiografia transesofágica, saturação venosa mista (SVO2), débito cardíaco por termodiluição intermitente e contínuo, pressões pulmonares e sistêmicas, transporte e consumo de oxigênio, tonometria gástrica e índices metabólicos foram medidos em determinados tempos. RESULTADOS : A manobra de recrutamento tipo insuflação sustentada não causou efeitos negativos cardiovasculares adicionais durante as 3 horas de protocolo. Indepedentemente da lesão pulmonar, durante o aumento progressivo de PEEP foi observado uma redução significativa (p<0.001) do índice cardíaco durante PEEP de 10 cmH2O (11.8 +- 7.4%), 15 cmH2O(25.5 +- 5.7%) e 20 cmH2O (36.1+- 5.1%), acompanhados de uma significativa redução da saturação venosa de oxigênio (p<0.001) durante PEEP de 15 e 20 cmH2O. Ao mesmo tempo, os volumes diastólicos finais dos ventrículos direito (VD) e esquerdo (VE) foram significativamente reduzidos durante PEEP de 10, 15 e 20 cmH2O (p<0.001) e durante PEEP de 20 cmH2O (p<0.001) respectivamente. A fração de ejeção do VD mostrou diminuição significativa durante PEEP de 10 cmH2O (p<0.05), 15 e 20 cmH2O (p<0.001) enquanto a fração de ejeção do VE permaneceu inalterada. O transporte de oxigênio foi significativamente reduzido (p<0.05) durante PEEP de 15 e 20 cmH2O, acompanhado por elevação da taxa de extração de oxigênio (p<0.001), sem comprometimento do consumo de oxigênio, lactato arterial sérico e tonometria gástrica. CONCLUSÕES: A instilação pulmonar de ácido clorídrico causou LPA caracterizada por queda na relação paO2/ FiO2, diminuição da complacência e hipertensão pulmonar. As insuflações sustentadas não causaram efeitos deletérios ao sistema cardiovascular durante as 3 horas de protocolo independentemente da presença de LPA. Os efeitos cardiovasculares negativos observados neste estudo foram resultantes do incremento de PEEP. Não houve diferença quanto aos efeitos cardiovasculares relacionados à PEEP entre os grupos. / INTRODUCTION: Alveolar collapse is a common finding in acute lung injury (ALI), leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Although the alveolar recruitment maneuver (ARM) has been the subject of much investigation over the last two decades, its use has currently become much more prevalent for treatment of patients with ALI. Elevated lung volumes and increased pleural pressures associated with ARM may undesirably affect pulmonary vascular resistance and cardiac performance. However, the benefits of ARM in oxygenation gain, weighed against negative hemodynamic effects, remain uncertain in part due to lack of data on the effects of ARM on cardiovascular function. The primary objective of this study was to verify, in an acute model of lung injury, the effects of one type of recruitment maneuver -sustained inflation- associated with different PEEP levels on cardiac function during a determined period of observation. DESIGN: Prospective, randomized, controlled experimental study. SETTING: Academic research laboratory. SUBJECTS: Thirty-two white landrace pigs.Interventions: Thirty-two anesthetized pigs were ventilated in volume-controlled mode. The animals were randomly allocated into four groups (G1-PEEP, G2-PEEP-ARM, G3-ALI-PEEP, G4-ALI-PEEP-ARM) of eight each. PEEP values were progressively increased and decreased from 5, 10, 15 and 20 cm H2O in all animals and were kept unaltered for 20 minutes at each plateau value. Three sustained recruitment maneuvers of 30 cmH2O with 20 seconds of duration each were apllied at each PEEP level in the G2-PEEP-ARM and G4-PEEP-ALI-ARM groups. To induce an acute injury, mainly in dependent lung regions, hydrochloric acid (0.05N, 4ml/kg ) was instillated juxt carinae by means of a flexible bronchoscope in groups G3-ALI-PEEP and G4-ALI-PEEP-ARM. Transesophageal echocardiography, mixed central venous saturation (SVO2), intermittent and continous cardiac output by thermodilution, systemic and pulmonary pressures, gastric tonometry, oxygen transportation, consumption and metabolic indexes were measured at established points. MEASUREMENTS AND MAIN RESULTS: Sustained alveolar recruitment maneuver did not provoke significant additional cardiovascular negative effects in selected groups during the 3 hours of the protocol. Independently of pulmonary lesion, during progressive PEEP augmentation, it was observed a significative (p<0.001) reduction (11.8 +- 7.4%) in cardiac index during 10 cmH2O of PEEP, (25.5?5.7%) and (36.1 +- 5.1%), during 15 and 20 cmH2O respectively, accompanied by a significant reduction in SVO2 (p<0.001) during 15 and 20 cmH2O of PEEP. At the same time, end diastolic volumes of right and left ventricles were significantly reduced during 10, 15 and 20 cmH2O of PEEP (p<0.001) and 20 cmH2O of PEEP (p<0.001) respectively. Ejection fraction of RV showed significant reduction during 10 cmH2O (p<0.05), 15 and 20 cmH2O (p< 0.001) of PEEP while LV ejection fraction remained unaltered. Oxygen transportation was significantly decreased (p<0.05) during 15 and 20 cmH2O of PEEP, acompanied by a significative oxygen extraction elevation, (p<0.001) without compromise of oxygen consumption, serum lactate, gastric tonometry and delta pCO2. CONCLUSIONS: Lung instillation of hydrochloric acid in two selected groups promoted an acute injury characterized by a drop in PaO2/FIO2 ratio, a decrease in respiratory compliance and pulmonary hypertension. During 3 hours of experimental protocol, ARM did not cause a significative hemodynamic embarrassment independently of presence of LPA. The negative cardiovascular effects during this study were related to a PEEP progression in the airway. No significant difference concerning cardiovascular effects related to PEEP was observed among the four established groups.

INTRODUÇÃO: Colapso alveolar é achado freqüente em lesão pulmonar aguda (LPA), levando ao aumento do shunt intrapulmonar e hipoxemia. Estratégias de tratamento atuais visam o recrutamento alveolar para melhora das trocas gasosas. Embora as manobras de recrutamento alveolar (MRA) sejam objetos de investigação nas últimas duas décadas, seu uso tem se tornado mais freqüente para o tratamento de pacientes com LPA. Volumes pulmonares e pressões pleurais elevados associados a MRA podem afetar a resistência vascular pulmonar e o trabalho cardíaco negativamente. Porém, o benefício da MRA na oxigenação, perante seus efeitos hemodinâmicos negativos, permanecem incertos devido à falta de informações dos efeitos cardiovasculares das MRAs. O objetivo deste estudo foi verificar, em modelo de LPA, os efeitos de um tipo de MRA- insuflação sustentada- associada a diferentes valores de PEEP no sistema cardiovascular durante um determinado período de observação. TIPO DE ESTUDO: estudo experimental prospectivo, controlado e randomizado. LOCAL: Laboratório de Anestesiologia Experimental- LIM 08. MATERIAL: Trinta e dois animais suínos. MÉTODO: Os animais anestesiados foram ventilados em modo volume-controlado e randomizados em quatro grupos (G1-PEEP; G2-PEEP-MRA; G3-LPA-PEEP; G4-LPA-PEEP-MRA) com oito animais cada. Os valores de PEEP foram progressivamente aumentados e diminuídos (5, 10, 15 e 20 cmH2O) em todos os animais e eram mantidos inalterados por 20 minutos em cada valor. Três insuflações sustentadas (MRA) de 30 cmH2O com duração de 20 segundos cada foram aplicadas em cada valor de PEEP nos grupos G2-PEEP-MRA e G4-LPA-PEEP-MRA. Para indução da LPA, principalmente em regiões pulmonares dependentes, o ácido clorídrico (0.05N, 4mL/kg) foi instilado na traquéia por meio de broncofibroscópio nos grupos G3-LPA-PEEP e G4-LPA-PEEP-MRA. Ecocardiografia transesofágica, saturação venosa mista (SVO2), débito cardíaco por termodiluição intermitente e contínuo, pressões pulmonares e sistêmicas, transporte e consumo de oxigênio, tonometria gástrica e índices metabólicos foram medidos em determinados tempos. RESULTADOS : A manobra de recrutamento tipo insuflação sustentada não causou efeitos negativos cardiovasculares adicionais durante as 3 horas de protocolo. Indepedentemente da lesão pulmonar, durante o aumento progressivo de PEEP foi observado uma redução significativa (p<0.001) do índice cardíaco durante PEEP de 10 cmH2O (11.8 +- 7.4%), 15 cmH2O(25.5 +- 5.7%) e 20 cmH2O (36.1+- 5.1%), acompanhados de uma significativa redução da saturação venosa de oxigênio (p<0.001) durante PEEP de 15 e 20 cmH2O. Ao mesmo tempo, os volumes diastólicos finais dos ventrículos direito (VD) e esquerdo (VE) foram significativamente reduzidos durante PEEP de 10, 15 e 20 cmH2O (p<0.001) e durante PEEP de 20 cmH2O (p<0.001) respectivamente. A fração de ejeção do VD mostrou diminuição significativa durante PEEP de 10 cmH2O (p<0.05), 15 e 20 cmH2O (p<0.001) enquanto a fração de ejeção do VE permaneceu inalterada. O transporte de oxigênio foi significativamente reduzido (p<0.05) durante PEEP de 15 e 20 cmH2O, acompanhado por elevação da taxa de extração de oxigênio (p<0.001), sem comprometimento do consumo de oxigênio, lactato arterial sérico e tonometria gástrica. CONCLUSÕES: A instilação pulmonar de ácido clorídrico causou LPA caracterizada por queda na relação paO2/ FiO2, diminuição da complacência e hipertensão pulmonar. As insuflações sustentadas não causaram efeitos deletérios ao sistema cardiovascular durante as 3 horas de protocolo independentemente da presença de LPA. Os efeitos cardiovasculares negativos observados neste estudo foram resultantes do incremento de PEEP. Não houve diferença quanto aos efeitos cardiovasculares relacionados à PEEP entre os grupos. / INTRODUCTION: Alveolar collapse is a common finding in acute lung injury (ALI), leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Although the alveolar recruitment maneuver (ARM) has been the subject of much investigation over the last two decades, its use has currently become much more prevalent for treatment of patients with ALI. Elevated lung volumes and increased pleural pressures associated with ARM may undesirably affect pulmonary vascular resistance and cardiac performance. However, the benefits of ARM in oxygenation gain, weighed against negative hemodynamic effects, remain uncertain in part due to lack of data on the effects of ARM on cardiovascular function. The primary objective of this study was to verify, in an acute model of lung injury, the effects of one type of recruitment maneuver -sustained inflation- associated with different PEEP levels on cardiac function during a determined period of observation. DESIGN: Prospective, randomized, controlled experimental study. SETTING: Academic research laboratory. SUBJECTS: Thirty-two white landrace pigs.Interventions: Thirty-two anesthetized pigs were ventilated in volume-controlled mode. The animals were randomly allocated into four groups (G1-PEEP, G2-PEEP-ARM, G3-ALI-PEEP, G4-ALI-PEEP-ARM) of eight each. PEEP values were progressively increased and decreased from 5, 10, 15 and 20 cm H2O in all animals and were kept unaltered for 20 minutes at each plateau value. Three sustained recruitment maneuvers of 30 cmH2O with 20 seconds of duration each were apllied at each PEEP level in the G2-PEEP-ARM and G4-PEEP-ALI-ARM groups. To induce an acute injury, mainly in dependent lung regions, hydrochloric acid (0.05N, 4ml/kg ) was instillated juxt carinae by means of a flexible bronchoscope in groups G3-ALI-PEEP and G4-ALI-PEEP-ARM. Transesophageal echocardiography, mixed central venous saturation (SVO2), intermittent and continous cardiac output by thermodilution, systemic and pulmonary pressures, gastric tonometry, oxygen transportation, consumption and metabolic indexes were measured at established points. MEASUREMENTS AND MAIN RESULTS: Sustained alveolar recruitment maneuver did not provoke significant additional cardiovascular negative effects in selected groups during the 3 hours of the protocol. Independently of pulmonary lesion, during progressive PEEP augmentation, it was observed a significative (p<0.001) reduction (11.8 +- 7.4%) in cardiac index during 10 cmH2O of PEEP, (25.5?5.7%) and (36.1 +- 5.1%), during 15 and 20 cmH2O respectively, accompanied by a significant reduction in SVO2 (p<0.001) during 15 and 20 cmH2O of PEEP. At the same time, end diastolic volumes of right and left ventricles were significantly reduced during 10, 15 and 20 cmH2O of PEEP (p<0.001) and 20 cmH2O of PEEP (p<0.001) respectively. Ejection fraction of RV showed significant reduction during 10 cmH2O (p<0.05), 15 and 20 cmH2O (p< 0.001) of PEEP while LV ejection fraction remained unaltered. Oxygen transportation was significantly decreased (p<0.05) during 15 and 20 cmH2O of PEEP, acompanied by a significative oxygen extraction elevation, (p<0.001) without compromise of oxygen consumption, serum lactate, gastric tonometry and delta pCO2. CONCLUSIONS: Lung instillation of hydrochloric acid in two selected groups promoted an acute injury characterized by a drop in PaO2/FIO2 ratio, a decrease in respiratory compliance and pulmonary hypertension. During 3 hours of experimental protocol, ARM did not cause a significative hemodynamic embarrassment independently of presence of LPA. The negative cardiovascular effects during this study were related to a PEEP progression in the airway. No significant difference concerning cardiovascular effects related to PEEP was observed among the four established groups.