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Thesis (doctoral)--Universitetet i Lund.

Made available in DSpace on 2016-07-01T13:10:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-09-12. Added 1 bitstream(s) on 2016-07-01T13:14:12Z : No. of bitstreams: 1 000866809.pdf: 1747343 bytes, checksum: 1bd62536c1ab61130611dd2e937d842f (MD5) / Os mecanismos envolvidos na remodelação cardíaca por sobrecarga de volume e o momento que a hipertrofia excêntrica apresenta prejuízo da função cardíaca são pouco conhecidos. Objetivos: a) Comparar alterações morfofuncionais, celulares (hipertrofia) e intersticiais (fibrose) em diferentes momentos da evolução da insuficiência aórtica; b) Verificar quais dos seguintes mecanismos estão envolvidos na remodelação cardíaca induzida pela IAo e em qual momento esta alteração acontece: alteração na metaloprotease 2 (MMP2) e do inibidor tecidual de metaloprotease 1 (TIMP1), alterações dos RNAs mensageiros específicos para a codificação das proteínas envolvidas na homeostase do cálcio (Fosfolambam, Ryr e Serca2a), alterações da expressão de proteínas fosfolambam e Serca2a do trânsito de cálcio. Casuística e Métodos: Estudo experimental com 64 ratos Wistar machos, 32 animais submetidos à insuficiência aórtica aguda (grupo IAo) e 32 animais a procedimento simulado (grupo Controle). Todos os animais foram seguidos com 1, 4, 8 e 12 semanas através de ecocardiogramas seriados e, após eutanásia, foram analisada morfometria do tecido cardíaco, atividade da MMP2 e TIMP-1, expressão gênica por Reação em Cadeia da Polimerase em Tempo Real das proteínas do trânsito de cálcio, expressão das proteínas Serca2a e fosfolambam pela técnica Western Blot. A análise estatística foi efetuada pela ANOVA de dois fatores; o pós teste de Holm Sidak; teste t grupo a grupo; Anova de 1 via, complementada por Tukey; correção por Bonferroni; teste de correlação de Spearman e teste de correlação de Pearson. Em todos os casos, o nível de significância adotado foi p<0,05. Resultados: Observou-se, na primeira semana, que o peso do VE e a pressão diastólica foi maior no grupo IAo. Na quarta semana, MMP2, TIMP-1, iMVE e fração de colágeno foram maiores no grupo IAo. A área do miócito e DDVE foram maiores... / The mechanisms that are involved in cardiac remodeling by volume overload and the moment the eccentric hypertrophy has impaired cardiac function are largely unknown. Objectives: a) to compare morphological, cell (hypertrophy) and interstitial (fibrosis) changes at different times of the evolution of aortic regurgitation (AR); b) to analyze which of the following mechanisms are involved in cardiac remodeling induced by aortic failure and at what moment this change takes place: change in the metalloprotease 2 (MMP 2) and tissue inhibitor of metalloproteinase 1 (TIMP1); changes of messenger RNAs to code proteins involved in calcium homeostasis (phospholamban, Ryr and SERCA2a), changes in expression of phospholamban and SERCA2a in the calcium transit. Methods: Experimental study with 64 male Wistar rats, 32 animals submitted to acute aortic regurgitation (AR group) and 32 animals sham procedure (Sham group). All animals were followed with 1, 4, 8 and 12 weeks by serial echocardiography and after euthanasia, were analyzed morphometry of cardiac tissue, the activity of MMP2 and TIMP-1, gene expression by RT-PCR of calcium homeostasis protein, SERCA2a and phospholamban expression by Western Blotting. Statistical analysis was performed by two-way ANOVA; the Holm Sidak post test; t test group to group; Anova one way, complemented by Tukey; Bonferroni correction; Spearman correlation test and Pearson's correlation test. In all cases, the significance level was set at p <0.05. Results: In the first week it was observed that weight of the LV and diastolic blood pressure were higher in the AR group. In the fourth week, MMP 2, TIMP-1, and collagen fraction were higher in the AR group. The myocyte area and left ventricle diastolic diameter (LVDD) were higher in the AR group compared to the sham group, from the eighth week. At weeks 8 and 12, the wall thickness (WT) was higher in the AR group than the...

Orientador: Paula Schmidt Azevedo Gaiolla / Coorientador: Marcos Ferreira Minicucci / Banca: Meliza Goi Roscani / Banca: Bertha Furlan Polegato / Banca: Paula Felippe Martinez / Resumo: Os mecanismos envolvidos na remodelação cardíaca por sobrecarga de volume e o momento que a hipertrofia excêntrica apresenta prejuízo da função cardíaca são pouco conhecidos. Objetivos: a) Comparar alterações morfofuncionais, celulares (hipertrofia) e intersticiais (fibrose) em diferentes momentos da evolução da insuficiência aórtica; b) Verificar quais dos seguintes mecanismos estão envolvidos na remodelação cardíaca induzida pela IAo e em qual momento esta alteração acontece: alteração na metaloprotease 2 (MMP2) e do inibidor tecidual de metaloprotease 1 (TIMP1), alterações dos RNAs mensageiros específicos para a codificação das proteínas envolvidas na homeostase do cálcio (Fosfolambam, Ryr e Serca2a), alterações da expressão de proteínas fosfolambam e Serca2a do trânsito de cálcio. Casuística e Métodos: Estudo experimental com 64 ratos Wistar machos, 32 animais submetidos à insuficiência aórtica aguda (grupo IAo) e 32 animais a procedimento simulado (grupo Controle). Todos os animais foram seguidos com 1, 4, 8 e 12 semanas através de ecocardiogramas seriados e, após eutanásia, foram analisada morfometria do tecido cardíaco, atividade da MMP2 e TIMP-1, expressão gênica por Reação em Cadeia da Polimerase em Tempo Real das proteínas do trânsito de cálcio, expressão das proteínas Serca2a e fosfolambam pela técnica Western Blot. A análise estatística foi efetuada pela ANOVA de dois fatores; o pós teste de Holm Sidak; teste t grupo a grupo; Anova de 1 via, complementada por Tukey; correção por Bonferroni; teste de correlação de Spearman e teste de correlação de Pearson. Em todos os casos, o nível de significância adotado foi p<0,05. Resultados: Observou-se, na primeira semana, que o peso do VE e a pressão diastólica foi maior no grupo IAo. Na quarta semana, MMP2, TIMP-1, iMVE e fração de colágeno foram maiores no grupo IAo. A área do miócito e DDVE foram maiores... / Abstract: The mechanisms that are involved in cardiac remodeling by volume overload and the moment the eccentric hypertrophy has impaired cardiac function are largely unknown. Objectives: a) to compare morphological, cell (hypertrophy) and interstitial (fibrosis) changes at different times of the evolution of aortic regurgitation (AR); b) to analyze which of the following mechanisms are involved in cardiac remodeling induced by aortic failure and at what moment this change takes place: change in the metalloprotease 2 (MMP 2) and tissue inhibitor of metalloproteinase 1 (TIMP1); changes of messenger RNAs to code proteins involved in calcium homeostasis (phospholamban, Ryr and SERCA2a), changes in expression of phospholamban and SERCA2a in the calcium transit. Methods: Experimental study with 64 male Wistar rats, 32 animals submitted to acute aortic regurgitation (AR group) and 32 animals sham procedure (Sham group). All animals were followed with 1, 4, 8 and 12 weeks by serial echocardiography and after euthanasia, were analyzed morphometry of cardiac tissue, the activity of MMP2 and TIMP-1, gene expression by RT-PCR of calcium homeostasis protein, SERCA2a and phospholamban expression by Western Blotting. Statistical analysis was performed by two-way ANOVA; the Holm Sidak post test; t test group to group; Anova one way, complemented by Tukey; Bonferroni correction; Spearman correlation test and Pearson's correlation test. In all cases, the significance level was set at p <0.05. Results: In the first week it was observed that weight of the LV and diastolic blood pressure were higher in the AR group. In the fourth week, MMP 2, TIMP-1, and collagen fraction were higher in the AR group. The myocyte area and left ventricle diastolic diameter (LVDD) were higher in the AR group compared to the sham group, from the eighth week. At weeks 8 and 12, the wall thickness (WT) was higher in the AR group than the... / Doutor

The optimal timing of valve replacement surgery in chronic severe aortic regurgitation (AR) has remained a major clinical problem in the management of these patients. Although the onset of symptoms is the generally accepted indication for aortic valve replacement (AVR), the unpredictable development of pre-symptomatic left ventricular (LV) dysfunction as a result of prolonged volume overload has resulted in numerous reports attempting to formulate a risk profile for these patients. Although aortic root and LV cineangiography have been the "gold standard" for defining the severity of AR and its effect on LV performance, serial follow-up by these means is impractical. More recently numerous non-invasive measures of LV size (echocardiogram) and function both at rest and on exercise (echocardiogram and equilibrium radionuclide angiocardiography., ERNA) have been serially utilised~ In these endeavours, the thinking has been clouded by a tendency to equate these two measures and failing to appreciate that apparent preoperative LV dysfunction (particularly on exercise) may be rapidly reversible by AVR and the consequent changes in LV loading conditions. This study was a prospective, sequential evaluation of left ventricular function using both non-invasive and invasive techniques in symptomatic and asymptomatic patients with isolated chronic, severe (4+) AR at cardiac catheterisation. The aims of the study were to (I) Identify differences in the clinical, echocardiographic, resting and exercise haemodynamic and I radionuclide measures of left ventricular function in symptomatic and asymptomatic patients with chronic severe A.R. with particular reference to the incidence of presymptomatic development of left ventricular dysfunction. (II) Critically evaluate the role of exercise stress (both isotonic and isometric) in the assessment of patients with chronic severe A.R. (III) Evaluate the influence of time (sequential studies) on the haemodynamic burden in asymptomatic patients. (IV) Study the impact of successful aortic valve replacement on the reversibility of abnormal pre-operative LV function in an attempt to predict which patients would benefit from this therapeutic intervention and whether operation for symptoms alone is the correct clinical practice.

Diss. Linköping : Linköpings universitet, 2008.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Description based on contents viewed June 24, 2007; title from title screen. Includes bibliographical references (p. 76-80).

Background: Chronic aortic regurgitation (AR) patients demonstrate left ventricular (LV) remodeling with increased LV mass and volume but may have a preserved LV ejection fraction (EF). We hypothesize that in chronic AR, global longitudinal systolic and diastolic function will be reduced despite a preserved LV EF. Methods: We studied with Doppler echocardiography 27 normal subjects, 87 patients with chronic AR with a LV EF > 50% (AR + PEF), 66 patients with an EF < 50% [AR + reduced LV ejection fraction (REF)] and 82 patients with hypertensive heart disease. LV volume, transmitral spectral and tissue Doppler were obtained. Myocardial velocities and their timing and longitudinal strain of the proximal and mid wall of each of the 3 apical views were obtained. Results: As compared to normals, global longitudinal strain was reduced in AR + PEF (13.8 ± 4.0%) and AR + REF (11.4 ±4.7%) vs. normals (18.4 ± 3.6%, both p < 0.001). As an additional comparison group for AR + PEF, global longitudinal strain was reduced as compared to patients with hypertensive heart disease (p = 0.032). The average peak diastolic annular velocity (e’) was decreased in AR + PEF (6.9 ± 3.3 cm/s vs. 13.4 ± 2.6 cm/s, p < 0.001) and AR + REF (4.8 ± 2.1 cm/s, p < 0.001). Peak rapid filling velocity/e’ (E/e’) was increased in both AR + PEF (14.4 ± 6.2 vs. 6.2 ± 1.3, p < 0.001) and AR + REF (18.8 ± 6.4, p <0.001 vs. normals). Independent correlates of global longitudinal strain (r = 0.6416, p < 0.001) included EF (p < 0.0001), E/e’ (p < 0.0001), and tricuspid regurgitation velocity (p = 0.0176). Conclusion: With chronic AR, there is impaired longitudinal function despite preserved EF. Moreover, global longitudinal strain was well correlated with noninvasive estimated LV filling pressures and pulmonary systolic arterial pressures.

Continuous-wave (CW) Doppler recordings of ascending aortic maximal blood flow acceleration (PkA), maximal velocity (PkV) and systolic velocity integral (SVI) were taken at each stage of a graded exercise treadmill test on two separate days with 30 physically active adult males. Signals were measured (Quinton Exerdop) for all cardiac cycles in the 3rd minute of each stage using a hand-held probe positioned at the suprasternal notch. A dedicated microcomputer, programmed to select "valid" beats on the basis of value consistency in the sample set, determined the acceptability of signals. No significant differences were found between the three trial means within each stage on either day for PkA, PkV or SVI. Significant (p <.01) intraclass reliability estimates ranged from r = 0.89 to 0.97 (Pk.A), r = 0.90 to 0.98 (PkV) and r = 0.85 to 0.95 (SVI) . Coefficients of variation were calculated at each stage to estimate the relative consistency of each measure. A gradual reduction of the coefficient of variation was observed for each blood flow measure between stages one and four. The test-retest (between days) reliability coefficients for PkA, PkV and SVI for stages one to four ranged between r = 0.51 to 0.78 (P <.004), but correlations for the pre-exercise baseline and stages five and six were lower. These results indicate that (1) PkA, PkV and SVI demonstrate greater measurement stability within each stage of a graded exercise test than is the case between separate days of measurement at the same stage; and (2) there is modest day-to-day response stability for clinical testing with the Doppler parameter of PkV. Reliability/stability was best in exercise stages which encompass the speed and grade range of 45.0 m•min⁻¹/10%. - 111.7 m•min⁻¹/14%, i.e., those in which all subjects can walk. / Master of Science

IntroductionThe young adult patients with aortic valve insufficiency undergo aortic valve replacement (AVR) and are forced to take anticoagulation medications for the rest of life due to prosthetic valve. This leads to many post-operative complications and drastic outcomes. Whereas, the in-vogue alternative of aortic valve repair (AVr) is available and a lot more beneficial as well.Especially considering the surgeon’s skills for selected repair procedure, selectively chosen patient with mild to moderate grades of aortic valve insufficiency and no significant comorbidities present for at least five (5) years or longer time. AimThe aim of this study was to affirm ‘if all kind of outcomes of aortic valve repair are beneficial alternative to aortic valve replacement (AVR) for the patients suffering from aortic valve insufficiency for at least five (5) years or longer time. Material and MethodsInternet search using standard key words of ‘Aortic Valve Repair and Outcomes’ was used to find both white literature (officially published literature) and grey literature (unpublished or ongoing study/literature) with human, adult, English language and studies published after January 1st 2007 as limitations. Inclusion criteria was adult patients with aortic insufficiency with aortic valve repair as intervention with outcomes at least greater than five (5) years were considered. All the data was extracted using Microsoft excel for windows and was analyzed using GraphPad Prisma. Results20 studies comprising of 5369 patients were included in this systemic review, which included 2 randomized control trails, 7 clinical prospective studies, 8 retrospective studies and 3 observational studies. ConclusionThis study suggests that aortic valve repair is a beneficial alternative available for younger adults suffering from aortic valve insufficiency in longer time.