Remodelamento cardíaco: análise seriada e índices de detecção precoce de disfunção ventricular

FUNDAMENTO: A estenose aórtica supravalvar (EAo) é utilizada para o estudo da remodelação cardíaca (RC) por sobrecarga pressórica. Nesse modelo, não estão claramente estabelecidos o comportamento da RC desde a fase inicial, nem os melhores parâmetros para a identificação da disfunção ventricular. OBJETIVOS: 1) Caracterizar, precoce e evolutivamente, as modificações morfofuncionais durante a RC em ratos com EAo e 2) identificar o índice mais sensível para detecção do momento do aparecimento da disfunção diastólica e sistólica do ventrículo esquerdo (VE). MÉTODOS: Ratos Wistar foram divididos em dois grupos - controle (GC, n=13) e EAo (GEAo, n=24) - e estudados nas 3ª, 6ª, 12ª e 18ª semanas pós-cirurgia. Os corações foram analisados por meio de ecocardiograma (ECO). RESULTADOS: Ao final do experimento, as relações do VE, do ventrículo direito e dos átrios com o peso corporal final foram aumentadas no GEAo. O ECO mostrou que o átrio esquerdo sofreu uma remodelação significativa a partir da 6ª semana. No GEAo, a porcentagem de encurtamento endocárdico apresentou queda significativa a partir da 12ª semana e a porcentagem de encurtamento mesocárdico, na 18ª semana. A relação onda E e onda A (E/A) foi superior no GC em comparação ao GEAo em todos os momentos analisados. CONCLUSÕES: O ventrículo esquerdo dos ratos com EAo, durante o processo de remodelação, apresentou hipertrofia concêntrica, disfunção diastólica precoce e melhoria da função sistólica, com posterior deterioração do desempenho. Além disso, constatou-se que os índices ecocardiográficos mais sensíveis para a detecção da disfunção diastólica e sistólica são, respectivamente, a relação E/A e a porcentagem de encurtamento endocárdico.

HIPERTENSAO ARTERIAL EM PACIENTES OBESOS COM HIPERTROFIA CARDIACA. EFEITOS DO CAPTOPRIL SOBRE A SENSIBILIDADE A INSULINA E HORMONIO DE CRESCIMENTO

Purpose. To evaluate the effects of captopril (Cpt) on carbohydrate metabolism and growth hormone (GH) in adults hypertensive obese patients with normal (NGT) or impaired (IGT) glucose tolerance and left ventricular hypertrophy. Methods. Ten patients (53 ± 8 years), 8 women and 2 men, white, body mass index (BMI) ≥ 26 kg/m2, left ventricular mass index (LVMI) > 135 g/m2 in man and > 110 g/m2 in woman, with diastolic blood pressure (DBP) 95-115 mmHg after 3 weeks of placebo, were identified by oral glucose tolerance test (OGTT-75 g) as either with NGT or IGT, and treated with Cpt 25 mg t.i.d. for 8 weeks. At the 8 weeks, dosage was increased to 50 mg b.i.d. if DBP > 90 mmHg or the decrease of the DBP < 10%, during the next 8 weeks. OGTT and clonidine tests (0,04 mg/kg) with determinations, every 30 minutes of glucose, insulin, and GH during 2 hours, were performed. Results. Cpt lowered SBP and DBP in the NGT group and IGT group. The LVMI and the left ventricular mass (LVM) decreased in the IGT group with no significant change in the NGT group. Cpt promoted in the IGT group decrease in the area under the curve (AUC) of glucose, and AUC of insulin, with increase of the AUC of the percent of the β cell function, AUC of HC, and insulin sensitivity index with no significantly change in the NGT group. Conclusion. Adults hypertensive obese patients with IGT had decreased significantly in mean fasting level of GH concentrations compared to age, race, and BMI matched hypertensive patients with NGT. Treatment with Cpt induced a significant increased of the GH, with improvement of the metabolism in patients with IGT.

Influência da suplementação de vitamina D na remodelação ventricular após o infarto do miocárdio

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Fatores de risco cardiovascular em mulheres com antecedente de pré-eclâmpsia e sua associação com hipertrofia miocárdica e espessamento médio-intimal de carótidas

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Washout hole for bi-ventricular assist device (BVAD) centrifugal blood pump

The shortage of donor hearts for patients with end stage heart failure has accelerated the development of ventricular assist devices (VAD) that act as a replacement heart. Mechanical devices involving pulsatile, axial and centrifugal devices have been proposed. Recent clinical developments indicate that centrifugal devices are not only beneficial for bridge to transplantation applications, but may also aid myocardial recovery. The results of a recent study have shown that patients who received a VAD have extended lives and improved quality of life compared to recipients of drug therapy. Unfortunately 25% of these patients develop right heart failure syndrome, sepsis and multi-organ failure. It was reported that 17% of patients initially receiving an LVAD later required a right ventricular assist device (RVAD). Hence, current research focus is in the development of a bi-ventricular assist device (BVAD). Current BVAD technology is either too bulky or necessitates having to implant two pumps working independently. The latter requires two different controllers for each pump leading to the potential complication of uneven flow dynamics and the requirements for a large amount of body space. This paper illustrates the combination of the LVAD and RVAD as one complete device to augment the function of both the left and right cardiac chambers with double impellers. The proposed device has two impellers rotating in counter directions, hence eliminating the necessity of the body muscles and tubing/heart connection to restrain the pump. The device will also have two separate chambers with independent rotating impeller for the left and right chambers. A problem with centrifugal impellers is the fluid stagnation underneath the impeller. This leads to thrombosis and blood clots.This paper presents the design, construction and location of washout hole to prevent thrombus for a Bi-VAD centrifugal pump. Results using CFD will be used to illustrate the superiority of our design concept in terms of preventing thrombus formation and hemolysis.

Passive control of a bi-ventricular assist device : an experimental and numerical investigation

For the last two decades heart disease has been the highest single cause of death for the human population. With an alarming number of patients requiring heart transplant, and donations not able to satisfy the demand, treatment looks to mechanical alternatives. Rotary Ventricular Assist Devices, VADs, are miniature pumps which can be implanted alongside the heart to assist its pumping function. These constant flow devices are smaller, more efficient and promise a longer operational life than more traditional pulsatile VADs. The development of rotary VADs has focused on single pumps assisting the left ventricle only to supply blood for the body. In many patients however, failure of both ventricles demands that an additional pulsatile device be used to support the failing right ventricle. This condition renders them hospital bound while they wait for an unlikely heart donation. Reported attempts to use two rotary pumps to support both ventricles concurrently have warned of inherent haemodynamic instability. Poor balancing of the pumps’ flow rates quickly leads to vascular congestion increasing the risk of oedema and ventricular ‘suckdown’ occluding the inlet to the pump. This thesis introduces a novel Bi-Ventricular Assist Device (BiVAD) configuration where the pump outputs are passively balanced by vascular pressure. The BiVAD consists of two rotary pumps straddling the mechanical passive controller. Fluctuations in vascular pressure induce small deflections within both pumps adjusting their outputs allowing them to maintain arterial pressure. To optimise the passive controller’s interaction with the circulation, the controller’s dynamic response is optimised with a spring, mass, damper arrangement. This two part study presents a comprehensive assessment of the prototype’s ‘viability’ as a support device. Its ‘viability’ was considered based on its sensitivity to pathogenic haemodynamics and the ability of the passive response to maintain healthy circulation. The first part of the study is an experimental investigation where a prototype device was designed and built, and then tested in a pulsatile mock circulation loop. The BiVAD was subjected to a range of haemodynamic imbalances as well as a dynamic analysis to assess the functionality of the mechanical damper. The second part introduces the development of a numerical program to simulate human circulation supported by the passively controlled BiVAD. Both investigations showed that the prototype was able to mimic the native baroreceptor response. Simulating hypertension, poor flow balancing and subsequent ventricular failure during BiVAD support allowed the passive controller’s response to be assessed. Triggered by the resulting pressure imbalance, the controller responded by passively adjusting the VAD outputs in order to maintain healthy arterial pressures. This baroreceptor-like response demonstrated the inherent stability of the auto regulating BiVAD prototype. Simulating pulmonary hypertension in the more observable numerical model, however, revealed a serious issue with the passive response. The subsequent decrease in venous return into the left heart went unnoticed by the passive controller. Meanwhile the coupled nature of the passive response not only decreased RVAD output to reduce pulmonary arterial pressure, but it also increased LVAD output. Consequently, the LVAD increased fluid evacuation from the left ventricle, LV, and so actually accelerated the onset of LV collapse. It was concluded that despite the inherently stable baroreceptor-like response of the passive controller, its lack of sensitivity to venous return made it unviable in its present configuration. The study revealed a number of other important findings. Perhaps the most significant was that the reduced pulse experienced during constant flow support unbalanced the ratio of effective resistances of both vascular circuits. Even during steady rotary support therefore, the resulting ventricle volume imbalance increased the likelihood of suckdown. Additionally, mechanical damping of the passive controller’s response successfully filtered out pressure fluctuations from residual ventricular function. Finally, the importance of recognising inertial contributions to blood flow in the atria and ventricles in a numerical simulation were highlighted. This thesis documents the first attempt to create a fully auto regulated rotary cardiac assist device. Initial results encourage development of an inlet configuration sensitive to low flow such as collapsible inlet cannulae. Combining this with the existing baroreceptor-like response of the passive controller will render a highly stable passively controlled BiVAD configuration. The prototype controller’s passive interaction with the vasculature is a significant step towards a highly stable new generation of artificial heart.

Exploring the parameter space of a rabbit ventricular action potential model to investigate the effect of variation on action potential and calcium transients

Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.