Orientador: Kleber Gomes Franchini / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T19:09:29Z (GMT). No. of bitstreams: 1 Lima_JoseMarcoNogueira_D.pdf: 1108641 bytes, checksum: 52decb99b4c7eb40cf6e3df4bdda5d47 (MD5) Previous issue date: 2006 / Resumo: O presente estudo tem como objetivo avaliar a influência da estimulação biventricular prolongada no pós-operatório de revascularização miocárdica em pacientes portadores de disfunção ventricular esquerda, FE = 40%, associada à duração do QRS menor ou igual a 130ms. Foram selecionados 21 pacientes dos quais 16 foram randomizados em dois grupos denominados: Grupo de estimulação biventricular (Grupo EBV) e Grupo Controle. Os dois grupos foram submetidos à monitorização contínua por um período de 12 horas com os seguintes parâmetros coletados: parâmetros hemodinâmicos sistêmicos (pressão arterial média, índice de resistência vascular sistêmica e temperatura), parâmetros hemodinâmicos cardíacos (débito cardíaco, índice cardíaco, índice do volume sistólico do ventrículo esquerdo e freqüência cardíaca) e parâmetros hemodinâmicos pulmonares (pressão em cunha de capilar pulmonar, pressão venosa central e índice de resistência vascular pulmonar). Para análise dos resultados foram empregados o teste t de Student, teste de Wilcoxon, teste exato de Fisher, teste de Wilks e MANOVA. A sincronização obtida através da estimulação biventricular sob captação atrial (sinusal) aumentou o índice cardíaco em conseqüência do aumento do volume sistólico. Observou-se também uma redução significativa da resistência vascular sistêmica em comparação com os pacientes não estimulados. Esses efeitos permaneceram nas 6 horas que se seguiram após a parada da estimulação no Grupo EBV. Não houve diferença estatisticamente significativa na pressão arterial média entre os grupos. O grupo estimulado apresentou uma menor pressão em cunha de capilar pulmonar do que o grupo controle durante o período da estimulação. Podemos concluir que a estimulação biventricular produziu nesses pacientes uma melhora do desempenho sistólico do ventrículo esquerdo por restaurar a coordenação da contratilidade cardíaca em conseqüência da sincronização independente da variável freqüência cardíaca e duração do QRS / Abstract: The present study aims to evaluate the influence of lengthened biventricular stimulation on the post-surgical period of myocardical revascularization in patients that carry left ventricular dysfunction, FE = 40%, associated to QRS endurance equal to or less than 130 ms. From a selection of 21 patients, 16 of which were randomized in 2 groups named: Biventricular Stimulation Group (EBV Group) and Control Group. Both groups have been submitted to a 12-hour continuous monitoring period, with the following parameters being collected: systemic hemodynamic parameters (mean arterial pressure, systemic vascular resistance index and temperature), cardiac hemodynamic parameters (cardiac output, cardiac index, left ventricle stroke volume index and heart rate) and pulmonary hemodynamic parameters (pulmonary artery wedge pressure, central venous pressure and pulmonary vascular resistance index). For the analysis of the results we have applied the Student's t test, Wilcoxon rank-sum test, Fisher's exact test, Wilks' test and MANOVA. The synchronization obtained through biventricular stimulation under atrial sense increased the cardiac index, as a consequence of the increased systolic volume. A significant reduction of systemic vascular resistance has also been observed, in comparison to that of the non-stimulated patients. These effects have endured for the 6-hour period that succeeded the interruption of the stimulation in the EBV Group. There was no statistically significant difference in the average blood pressure between the groups. The stimulated group presented a lower pulmonary artery wedge pressure than that of the control group over the stimulation period. We can concluded the biventricular stimulation has produce an improvement on the systolic performance as the left ventricular do the restoration of the ventricular contractibility as a consequence of a synchronization that the not depend the frequency and the QRS lasting / Doutorado / Medicina Experimental / Doutor em Fisiopatologia Medica

Orientador: Orlando Petrucci Junior / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T10:51:42Z (GMT). No. of bitstreams: 1 Souza_FernandoSergioOlivade_D.pdf: 1025341 bytes, checksum: 15ba5e4c6177129ac03b697eb1f59cb9 (MD5) Previous issue date: 2008 / Resumo: A estimulação elétrica biventricular apresenta bons resultados no tratamento da insuficiência cardíaca congestiva refratária em portadores de cardiomiopatia dilatada com distúrbios de condução interventricular. OBJETIVO: Apresentar proposição utilizando técnica original simplificada para o implante de eletrodo de estimulação ventricular esquerda epicárdica, baseado na anatomia radiológica e no eletrograma intracavitário,enfatizando o componente atrial, demonstrando o resultado, complicações, ressaltando tempo total de utilização de fluoroscópio. CASUÍSTICA E MÉTODO: De Outubro de 2001 a Março de 2007 foram realizados 234 implantes de marca-passo biventricular em pacientes previamente selecionados, utilizando-se anatomia radiológica e observação de eletrograma intracavitário, dando-se prioridade ao componente atrial, demonstrando a taxa de sucesso, complicações e tempo total de utilização de radioscopia. RESULTADOS: O implante do sistema, utilizando-se a estimulação do ventrículo esquerdo via seio coronariano não foi possível em 19(8,1%) pacientes. Em 30(12,8%) pacientes foram observadas dificuldades na canulação do óstio coronário e em 52(22%) pacientes observaram-se dificuldades de progressão do eletrodo através do seio coronário. O tempo médio de utilização de radioscopia foi 18,69(±15,2) min. CONCLUSÃO: A utilização da técnica simplificada para cateterização do seio coronário sem utilização de bainha, baseada na anatomia radiológica e no eletrograma intracavitário, enfatizando o componente atrial, no tratamento de portadores de cardiomiopatia dilatada avançada, pela terapia de ressincronização cardíaca, demonstrou resultado satisfatório, índice de complicações pequeno, e baixa exposição do operador a radiação ionizante / Abstract: Biventricular pacing has present good results in treatment of congestive cardiac heart failure in patients with dilated miocardyopathy and interventricular conduction disturbance. PURPOSE: to present a proposal of using a original simplified technique for left epicardial ventricular lead stimulation, based on the radiological imaging of the anatomy and intracavitary electrogram, emphasizing the atrial component, showing the results, complications, highlighting the total fluoro time. METHODS: From October, 2001 up to March, 2007, 234 biventricular pacemaker implantations were performed in previously selected patients, using radiological anatomy and observation of the intracavitary electrogram, focusing on the atrial component, and showing the success rate, complications and total time of radioscopy utilization. RESULTS: The implantation of the system using left ventricular pacing via coronary sinus was not possible in 19(8,1%) patients. Difficulties on the cannulation of the coronary ostium were felt in 30(12,8%) patients and difficulties of lead advancement through the coronary sinus were felt in 52(22%) patients. The mean time of radioscopy utilization was 18.69(±15,2) min. CONCLUSION: the use of a simplified technique for coronary sinus cannulation without the aid of a sheath, based on the radiological imaging of the anatomy and intracavitary electrogram, emphasizing the atrial component, for the treatment of advanced dilated cardiomyopathy patients with cardiac resynchronization therapy, has shown satisfactory results, low incidence of complications, and low exposure of the operator to ionizing radiation / Doutorado / Cirurgia / Doutor em Cirurgia

The sinus node (SN) is the natural pacemaker of the heart. In the human, the SN is surrounded by the paranodal area (PNA), the function of which is currently unknown. The PNA may act as subsidiary atrial pacemakers (SAP) and become the dominant pacemaker during sinus node dysfunction (SND). Creation of an animal model of SND allows characterisation of SAP, which can be a target for novel treatment strategies other than the currently available electronic pacemakers. I developed a large animal model of SND by ablating the SN in the goat and validated it by mapping the location of the newly emergent SAP. Functional characterisation of the SAP revealed reduced atrioventricular (AV) conduction time consistent with a location of the SAP close to the AV junction. SAP recovery time showed an initially significant prolongation compared to the SN recovery time, followed by a gradual decrease over 4 weeks. SAP pauses, and temporary reliance on electronic pacemaker activity have also been demonstrated then disappeared over time, suggesting possible modulation, maturation of the SAP. Structural characterisation of the SN revealed an extensive pacemaking complex within the right atrium (RA); the SN was surrounded by the PNA, extending down to the inferior vena cava (IVC) and into the interatrial groove. The PNA had a histological appearance that is intermediate to the SN and the RA. 3D reconstruction demonstrated, for the first time in a large animal model, an extensive and almost complete circle of pacemaking tissue at the junction of the embryologically different sinus venosus and the muscular right atrium. The SAP emerged in a location close to the IVC along the crista terminalis. Expression of key ion channel proteins in the SAP showed abundance of the pacemaker channel (HCN4) and the sodium/calcium exchanger (NCX1) compared to RA, similar to the expression pattern of the SN. The expression of the main high conductance connexin (Cx43) was not significantly different between SAP and RA, and both expressed Cx43 more abundantly than the SN.Conclusion: Destruction of the sinus node in this experimental model resulted in the generation of chronic SAP activity in the majority of the animals. The SAP displayed maturation over time and located in the inferior part of the RA, in the same area where the PNA was found in controls, suggesting the role of PNA as the dominant pacemaker in sinus node dysfunction. The SAP in the goat constitutes a promising stable target for electrophysiological modification to construct a fully functioning biological pacemaker.

Membrane diversity associated with variation in body mass and body temperature of hymenopterans was investigated. Body mass of organisms affects most aspects of their biology, including physiological traits. One trait influenced by mass is metabolic rate, but the basis for its variation among organisms remains unclear. Recent work revealed that membrane phospholipid composition varies systematically with body mass: smaller vertebrates with higher mass-specific metabolic rates have more fluid membranes containing more long chains of polyunsaturated fatty acids (PUFA) and less monounsaturated fatty acids (MUFA). This “membrane pacemaker” theory of metabolism has recently been challenged by a lack of link between metabolic rate and membrane composition. To test this relationship, we have quantified the membrane lipid composition of 22 species of Panamanian orchid bees with a 22-fold range in mass. Results incorporating phylogenetic analysis show significant relationships for 18:1 (MUFA) and 18:3 (PUFA) with body mass that are consistent with the “pacemaker” theory, and unexpected relationships with saturated fatty acids (SFA). Moreover, changes in membrane fatty acid composition with temperature are a strategy in ectothermic poïkilotherms that is part of the “homeoviscous adaptation” model. Here, we report systematic variations in fatty acid composition linked with thoracic temperature excess in North American Hymenopterans, a novel discovery in these heterotherms. These findings are discussed in the context of diet, metabolism and lifespan.

Endogenously produced carbon monoxide (CO) is an important gaseous signalling molecule which regulates a variety of cardiorespiratory functions. CO is produced in cells by the heme oxygenase (HO) family of proteins by the breakdown of heme into equimolar amounts of CO, bilirubin and Fe2+. My thesis focuses on the hypoxia- and hyperoxia-inducible HO-1/CO system exclusively and aims to provide the first evidence that the HO-1/CO system is involved in cardiorespiratory control in the zebrafish (Danio rerio) and goldfish (Carassius auratus). Overall, I hypothesise that the HO-1/CO system acts as a negative regulator of cardiorespiratory function in fish. Using immunohistochemistry, I was able to characterise the distribution of HO-1 and thus reveal the potential for endogenous CO production (from heme breakdown) in branchial and skin neuroepithelial cells (NECs; putative O2 chemoreceptors) and associated innervation as well as the heart of the developing zebrafish larva. The presence of HO-1 in these structures suggests the likelihood of specific and localized production of CO in fish. To assess the functional significance of the HO-1/CO system in control of cardiorespiratory function, I used pharmacological and gene knock down approaches to diminish HO-1 activity, and presumably endogenous CO production, in adult and larval fish, respectively. The results from these experiments provided evidence that 1) CO has an inhibitory influence on ventilation in goldfish and zebrafish but that its function is temperature- and species-dependent and 2) showed that the HO-1/CO system tonically inhibits cardiac activity in larval zebrafish.

Current pacemakers allow check up of their function using telemonitoring. Even so, the majority of the checks are carried out on an outpatient basis. It is not known, whether remote follow ups of the patients after pacemaker replacement would be cost-effective compared to in-office controls. A retrospective analysis of patients files of patients after pacemaker replacement in 2002-2005 in Faculty hospital of Kralovske Vinohrady was done. A total of 1407 records from the years 2002-2015 was analyzed. It was demonstrated that the vast majority (96%) of planned controls of these patients was not associated with a change of program of the pacemaker, so it could be performed remotely. Based on the obtained data a model, which compared the cost-effectiveness of outpatient and theoretically made remote controls of pacemakers was created. Using an analysis of cost minimalization, it was found that the remote controls of pacemakers, was not associated with a significant reduction of the costs compared to the ambulatory controls.

Die bildgebende Diagnostik im Magnetresonanztomographen ist für Träger implantierter, nicht MR-fähiger Herzschrittmacher und Cardioverter/Defibrillatoren potentiell risikoreich. Durch das starke externe Magnetfeld und die elektromagnetischen Signale des MRT-Gerätes können die antibradykarden und –tachykarden Therapiesysteme in ihrer korrekten Funktion erheblich gestört und durch die Antennenwirkung der Sonden myokardiale Schädigungen hervorgerufen werden. In der vorliegenden Arbeit sind bei Trägern derartiger Implantate deren wichtigste Funktionsparameter vor und nach einer jeweiligen Untersuchung im MRT telemetrisch ermittelt worden. Anhand der statistischen Auswertung der prä- und postprozedualen Messwerte für Wahrnehmung (Sensing), Reizschwelle und Elektrodenimpedanz wurde der Einfluss einer MRT-Untersuchung auf die regelrechte Funktion der Herzschrittmacher- und ICD-Aggregate untersucht. Ein weiteres Augenmerk galt im Allgemeinen der grundsätzlichen Durchführbarkeit des Verfahrens und eventuellen Komplikationen hinsichtlich unzureichender Patientensicherheit. Zum einen konnte gezeigt werden, dass nach sorgfältiger Abwägung von Risiko und Nutzen der Untersuchung, sowie entsprechenden Sicherheitsvorkehrungen, die MRT komplikationslos durchführbar ist. Weiterhin konnte keine Beeinträchtigung der regelrechten Funktion der Aggregate nachgewiesen werden.

Symptomatic sinus bradycardia, due to either sick sinus syndrome or vagotonia, can be familial, affecting several members of a family. We report an 18-year-old male patient with palpitations and limited exercise capacity who was noted to have severe sinus bradycardia. His resting heart rate was 40/min, with normal PR and corrected QT intervals, and sinus pauses up to 6 seconds during sleep. Exercise treadmill test and pharmacologic autonomic blockade during electrophysiologic studies abolished the bradycardia, suggestive of vagotonia rather than intrinsic sinus node dysfunction. This patient's father and a female cousin had a similar clinical history but associated with syncope and severe sinus bradycardia. The mode of transmission appeared to be autosomal dominant. All three have permanent demand pacemakers implanted and are asymptomatic.

Lipopolysaccharide (LPS) has been implicated in sepsis-mediated heart failure and chronic cardiac myopathies. We determined that LPS directly and reversibly affects cardiac myocyte function by altering regulation of intracellular Ca2+ concentration ([Ca2+]i) in immortalized cardiomyocytes, HL-1 cells. [Ca2+]i oscillated (<0.4 Hz), displaying slow and transient components. LPS (1 μg/ml), derived either from Escherichia coli or from Salmonella enteritidis, reversibly abolished Ca2+ oscillations and decreased basal [Ca 2+]i by 30-40 nM. HL-1 cells expressed Toll-like receptors, i.e., TLR-2 and TLR-4. Thus, we differentiated effects of LPS on [Ca2+]i and Ca2+ oscillations by addition of utlrapure LPS, a TLR-4 ligand. Ultrapure LPS had no effect on basal [Ca 2+]i, but it reduced the rate of Ca2+ oscillations. Interestingly, Pam3CSK4, a TLR-2 ligand, affected neither Ca 2+ parameter, and the effect of ultrapure LPS and Pam3CSK4 combined was similar to that of utlrapure LPS alone. Thus, unpurified LPS directly inhibits HL-1 calcium metabolism via TLR-4 and non-TLR-4-dependent mechanisms. Since others have shown that endotoxin impairs the hyperpolarization-activated, nonselective cationic pacemaker current (If), which is expressed in HL-1 cells, we utilized whole cell voltage-clamp techniques to demonstrate that LPS (1 μg/ml) reduced If in HL-1 cells. This inhibition was marginal at physiologic membrane potentials and significant at very negative potentials (P < 0.05 at -140, -150, and -160 mV). So, we also evaluated effects of LPS on tail currents of fully activated If. LPS reduced the slope conductance of the tail currents from 498 ± 140 pS/pF to 223 ± 65 pS/pF (P < 0.05) without affecting reversal potential of -11 mV. Ultrapure LPS had similar effect on If, whereas Pam3CSK4 had no effect on If. We conclude that LPS inhibits activation of I f, enhances its deactivation, and impairs regulation of [Ca 2+]i in HL-1 cardiomyocytes via TLR-4 and other mechanisms.

Moderne Herzschrittmacher sind mit zahlreichen Algorithmen ausgestattet, die sie zu bemerkenswerten therapeutischen und diagnostischen Werkzeugen machen. Die zunehmende Komplexität bringt jedoch unbeabsichtigt neue Herausforderungen mit sich. In dieser Arbeit beschreiben wir eine neue Herzschrittmacher-Induzierte Arrhythmie die oft zum Vorhofflimmern führt.:1. Introduction................................................................................................ 3 1.1. A flashback to the beginning of cardiac pacemakers ............................. 3 1.2. Early pacemakers and significant advances .......................................... 5 1.3. Fast-forward to modern pacemakers ...................................................... 6 1.4. Current challenges .................................................................................. 8 1.5. Identification of a new pacemaker induced arrhythmia .......................... 10 1.6. Methods and results ............................................................................... 11 1.7. Patient characteristics ............................................................................ 13