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There is epidemiological and experimental evidence suggesting that exercise training may reduce the mortality rate from coronary heart disease, in particular the sudden death rate, and that it may improve the peak functional capacity of the heart. This thesis includes experimental work that is relevant to both these questions.

Ventricular fibrillation (VF) is a lethal heart rhythm that leads to cardiac arrest. It has been shown that amplitude spectral area (AMSA) in prolonged VF correlates with success of resuscitation. This study will compare traditional resuscitation with a novel resuscitation algorithm using AMSA and end-tidal carbon dioxide (ETCO2) to time defibrillations.VF will be induced in 60 swine. Resuscitation will commence after 10 minutes of untreated VF. Cases will receive defibrillation if AMSA is >19.8 mVHz and ETCO2 >20 mm of Hg, otherwise chest compressions will continue for another 90 seconds. Controls will have standard resuscitation. Sub group analysis will include effect of induced myocardial infarction (MI).End points will include survival, neurologic scores, duration of resuscitation efforts, and number of defibrillations.This experiment will establish whether using AMSA and ETCO2 to time defibrillations results in superior resuscitation compared with standard techniques.

When excitable cardiac tissue is electrically paced at a sufficiently high rate, the duration of excitation can alternate from beat to beat despite a constant stimulation period. This rhythm, known as alternans, has been identified as an early stage in a sequence of increasingly complex instabilities leading to the lethal arrhythmia ventricular fibrillation (VF). This connection served as as a motivation for research into the control of alternans as a strategy to prevent VF. Control methods that do not use a model of the dynamics have been used for the suppression of alternans. However, these methods possess limitations. In this thesis we study theoretically model-based control techniques with the goal of developing protocols that would overcome the shortcomings of non model-based approaches. We consider one dimensional tissue in two different geometrical configurations: a ring and a fiber with free ends (open fiber). We apply standard control methods for linear time invariant systems to a stroboscopic map of the linearized dynamics around the normal rhythm. We found that, in the ring geometry, model-based control is able to suppress alternans faster and with lower current, thereby reducing the risk of tissue damage, compared with non-model-based control. In the open fiber, model-based control is able to suppress alternans for longer fibers and higher pacing frequencies in comparison with non-model-based control. The methodology presented here can be extended to two- and three-dimensional tissue, and could eventually lead to the suppression of alternans on the entire ventricles.

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Orientador: Sebastião Araujo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T01:38:54Z (GMT). No. of bitstreams: 1 Ovalle_CarlosCezarIvoSant'Ana_D.pdf: 918971 bytes, checksum: 7890aba34116748396efbad3ac6c01f5 (MD5) Previous issue date: 2011 / Resumo: Fundamento: O papel de vasopressores não-adrenérgicos na ressuscitação cardiopulmonar (RCP) permanece controverso. Objetivo: O objetivo do estudo foi avaliar a eficácia da terlipressina (TP) vs. adrenalina (ADR) em aumentar a pressão de perfusão coronariana (PPCor) e o retorno da circulação espontânea (RCE) na RCP em suínos. Métodos: Sob anestesia ketamina/tiopental, fibrilação ventricular foi induzida em 44 porcos fêmeas imaturos, permanecendo não-assistida por 10min, seguido de 2min de RCP-manual (100 compressões/10 ventilações/min com ar). Os animais foram então alocados em quatro grupos, recebendo: 1) ADR (45?g/kg); 2) salina-placebo (10mL); 3) TP (20?g/kg); 4) TP (20?g/kg) + ADR (45?g/kg). Desfibrilação foi realizada 2min apos, observando-se os animais sobreviventes por um período de 30min. ECG, PA sistêmica, PAD e PEtCO2 foram monitorados continuamente. Resultados: A TP não diferiu do placebo quanto aos efeitos na PPC, com baixas taxas de RCE em ambos os grupos (1/11 vs. 2/11; p=NS). A ADR aumentou a PPC de 13 ± 12 para 54 ± 15mmHg (p<0,0001), efeito similar a TP+ADR (de 21 ± 10 para 45 ± 13mmHg; p<0,0001), com altas taxas de RCE/sobreviventes em ambos os grupos (10/11 vs. 9/11, respectivamente). Entre os sobreviventes, maior PAM foi observada no grupo TP+ADR vs. ADR (105 ± 19mmHg vs. 76 ± 21mmHg; p=0,0157). Conclusões: ADR e TP+ADR foram efetivas para aumentar a PPC/RCE neste modelo experimental, mas a TP isolada não foi diferente do placebo. Contudo, nos animais sobreviventes do grupo TP+ADR observou-se uma maior estabilidade hemodinâmica após a RCE, sugerindo que a TP possa ser uma medicação útil no manuseio da hipotensão pós-RCP / Abstract: Background: The role of non-adrenergic vasopressors during cardiopulmonary resuscitation (CPR) remains controversial. Objective: The aim of the study was to compare the efficacy of terlipressin (TP) vs. adrenaline (ADR) to increase coronary perfusion pressure (CPP) and the return of spontaneous circulation (ROSC) during CPR in pigs. Methods: Under ketamine/thiopental anesthesia, ventricular fibrillation was induced in 44 immature female pigs remaining non-assisted for 10min, followed by 2min of manual closed-chest CPR (100 thoracic compressions and 10 ventilation/min with air). The animals were then randomized into four groups, receiving: 1) ADR (45?g/kg); 2) saline-placebo (10mL); 3) TP (20?g/kg); 4) TP (20?g/kg) + ADR (45?g/kg). Defibrillation was attempted 2min later. Surviving animals were observed during 30min. EKG, systemic AP, RA pressure and PEtCO2 were continuously recorded. Results: TP was not different from placebo regarding their effects on CPP, with low ROSC rates in both groups (1/11 vs. 2/11, respectively; p=NS). ADR increased CPP from 13 ± 12 to 54 ± 15mmHg (p<0.0001), similar to TP+ADR (from 21 ± 10 to 45 ± 13mmHg; p<0.0001), with high rates of ROSC/survival in both groups (10/11 vs. 9/11, respectively). Among surviving animals, a greater MAP was recorded in TP+ADR when compared with ADR (105 ± 19mmHg vs. 76 ± 21mmHg; p=0.0157). Conclusions: ADR and TP+ADR were highly effective to increase CPP and ROSC in this experimental CPR model, but TP alone was not different from placebo. Moreover, surviving animals in TP+ADR group showed greater hemodynamic stability after ROSC, suggesting that TP could be a potential useful drug for post-CPR hypotension/shock management / Doutorado / Fisiopatologia Cirúrgica / Doutor em Ciências

Orientadores: José Wilson Magalhães Bassani, Rosana Almada Bassani / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação / Made available in DSpace on 2018-08-18T15:44:00Z (GMT). No. of bitstreams: 1 Viana_MarcelodeAlmeida_M.pdf: 2859747 bytes, checksum: 35c1831b1c265e9788b9dcc01dfdbd47 (MD5) Previous issue date: 2011 / Resumo: A fibrilação ventricular (FV) é um tipo de arritmia cardíaca com alto potencial letal, cujo único tratamento eficaz conhecido é a desfibrilação elétrica, ou seja, aplicação de choques de alta intensidade. Este procedimento, no entanto, pode causar sério comprometimento da função cardíaca por afetar deleteriamente as células miocárdicas, o que pode resultar em insucesso da ressuscitação. Neste trabalho foi desenvolvida e testada uma instrumentação específica para o estudo de uma nova abordagem de desfibrilação elétrica cardíaca (estimulação multidirecional), que permitiu o chaveamento de choques sequenciais temporalmente defasados durante o mesmo ciclo estimulatório cardíaco, os quais foram aplicados a três pares de eletrodos em diferentes direções. A instrumentação foi testada in vivo, na desfibrilação direta do coração de suínos. A desfibrilação multidirecional permitiu uma redução em 20% da intensidade requerida dos choques, quando comparada à convencional (monodirecional) em uma ampla faixa de probabilidade de sucesso desfibrilatório. Mesmo para uma probabilidade de sucesso de 90%, os níveis de energia requeridos para a reversão da FV foram significativamente menores com a estimulação multidirecional (4,25 ± 0,63 J) do que com a estimulação monodirecional (5,09 ± 0,43 J, respectivamente; P< 0,05). Deste modo, a estimulação multidirecional demonstra ser uma importante inovação para permitir um tratamento desfibrilatório mais eficiente e seguro / Abstract: Ventricular fibrillation (VF) is a potentially lethal cardiac arrhythmia, for which the only known effective treatment is electrical defibrillation, i.e. application of high-intensity electric shocks to the heart. Such shocks, however, may exert deleterious effects on myocardial cells, which may impair cardiac function and result in resuscitation failure. In this work, a specific instrumentation was developed for the study of a new approach of cardiac defibrillation (multidirectional stimulation), in which shocks were switched and applied to three pairs of electrodes placed in different directions. The instrumentation was tested in vivo for direct defibrillation of pig hearts. With multidirectional defibrillation, the shock intensity required for defibrillation was 20% lower compared to conventional (monodirectional) defibrillation for a wide range of successful defibrillation probability. Even for a probability as high as 90%, the energy levels required for VF reversal were significantly lower with multidirectional stimulation than with monodirectional stimulation (4.25 ± 0.63 ± J vs. 5.09 0.43 J, respectively; P < 0.05). Thus, multidirectional stimulation seems to be an important innovation toward a more efficient and safer defibrillation treatment. / Mestrado / Engenharia Biomedica / Mestre em Engenharia Elétrica

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Out-of-hospital cardiac arrest (OHCA) is a significant public health problem in most westernized industrialized nations. In spite of national and international guidelines for cardiopulmonary resuscitation and emergency cardiac care, the overall survival of patients with OHCA was essentially unchanged for 30 years--from 1978 to 2008 at 7.6%. Perhaps a better indicator of Emergency Medical System (EMS) effectiveness in treating patients with OHCA is to focus on the subgroup that has a reasonable chance of survival, e.g., patients found to be in ventricular fibrillation (VF). But even in this subgroup, the average survival rate was 17.7% in the United States, unchanged between 1980 and 2003, and 21% in Europe, unchanged between 1980 and 2004. Prior to 2003, the survival of patients with OHCA, in VF in Tucson, Arizona was less than 9% in spite of incorporating previous guideline recommendations. An alternative (non-guidelines) approach to the therapy of patients with OHCA and a shockable rhythm, called Cardiocerebral Resuscitation, based on our extensive physiologic laboratory studies, was introduced in Tucson in 2003, in rural Wisconsin in 2004, and in selected EMS areas in the metropolitan Phoenix area in 2005. Survival of patients with OHCA due to VF treated with Cardiocerebral Resuscitation in rural Wisconsin increased to 38% and in 60 EMS systems in Arizona to 39%. In 2004, we began a statewide program to advocate chest compression-only CPR for bystanders of witnessed primary OHCA. Over the next five years, we found that survival of patients with a shockable rhythm was 17.7% in those treated with standard bystander CPR (mouth-to-mouth ventilations plus chest compression) compared to 33.7% for those who received bystander chest-compression-only CPR. This article on Cardiocerebral Resuscitation, by invitation following a presentation at the 2011 Danish Society Emergency Medical Conference, summarizes the results of therapy of patients with primary OHCA treated with Cardiocerebral Resuscitation, with requested emphasis on the EMS protocol.