Ischemic heart disease is a leading cause of death worldwide. Osteopontin (OPN), a cell-secreted extracellular matrix protein, is suggested to play a cardioprotective role in mouse models of ischemic heart disease. The objective of this study was to examine the role of OPN in modulation of systolic and diastolic functional parameters of the heart following mouse ischemia/reperfusion (I/R) injury. For this, wild-type (WT) and OPN-knockout (KO) mice aged approximately 4 months were subjected to cardiac ischemia for 45 minutes by the ligation of the left anterior descending coronary artery (LAD) followed by reperfusion of LAD by snipping the ligature. Heart function was measured using echocardiography at baseline, 1, 3, 7, 14, and 27 days post-I/R injury. M-mode echocardiographic images were used to calculate % fractional shortening [%FS], % ejection fraction [%EF], end-systolic volume [ESV], and end-diastolic volume [EDV], while pulsed wave Doppler images were used to measure aortic ejection time [AET], isovolumic relaxation time [IVRT], and total systolic time [TST]. Velocity of circumferential fiber shortening (Vcf) was calculated using FS and AET. I/R injury significantly decreased %EF and %FS in both WT and KO groups at all time points (1, 3, 7, 14, and 27 days post-I/R) versus the baseline. However, the decrease in % EF and %FS was significantly greater in KO-I/R group versus WT-I/R at 3, 7, 14 and 27 days post-I/R. I/R-mediated increase in ESV and EDV were significantly greater in KO-MI group versus WT-MI 3 day post-I/R. AET was significantly higher in WT-I/R group 27 days post-I/R versus baseline. However, AET was significantly lower in KO-I/R group 3 and 27 days post-I/R versus WT-I/R. IVRT was significantly higher in KO-I/R group 27 days post-I/R vs baseline. However, IVRT was significantly lower in KO-I/R group 1 day post-I/R vs WT-I/R. TST remained unchanged in WT and KO groups post-I/R versus their respective baseline groups. However, TST was significantly lower in KO-I/R group versus WT-I/R at 3 days post-I/R. Vcf was significantly higher at basal levels in the KO versus WT mice. I/R injury decreased Vcf in both groups versus their baseline at all time-points. These data provide evidence that lack of OPN deteriorates systolic and diastolic functional parameters of the heart following I/R injury, suggesting a cardioprotective role of OPN in myocardial remodeling post-IR.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2014-12-18T13:43:38Z No. of bitstreams: 1 Dissertação - Rogério Gomes Furtado - 2013.pdf: 8231426 bytes, checksum: 27a3b18b8a08192dc1223e0b4a48c1b8 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-12-18T14:07:17Z (GMT) No. of bitstreams: 1 Dissertação - Rogério Gomes Furtado - 2013.pdf: 8231426 bytes, checksum: 27a3b18b8a08192dc1223e0b4a48c1b8 (MD5) / Made available in DSpace on 2014-12-18T14:07:19Z (GMT). No. of bitstreams: 1 Dissertação - Rogério Gomes Furtado - 2013.pdf: 8231426 bytes, checksum: 27a3b18b8a08192dc1223e0b4a48c1b8 (MD5) Previous issue date: 2013-06-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Objective: To evaluate the prevalence of systolic and diastolic right ventricular (RV) in patients with indeterminate form of Chagas Disease (FDIC) and compare with asymptomatic patients without this condition. Methods: An observational, case-control, descriptive and prevalent study in which 91 patients were divided into 2 groups: group I (normal n = 31) and group II (FIDC normal cardiac n = 61). Were performed 2D Doppler echocardiography in adult patients, applying the criteria assessment of systolic and diastolic RV. Results: The general characteristics of both groups: age (39.73 ± 12.94 vs 45.32 ± 12.36, p = 0.071), weight in kg (71.29 ± 14.91 vs 67.66 ± 12, 37 with p = 0.270), Height in cm (159.24 ± 32.63 vs 156.88 ± 30.56, p = 0.749), ISC (1.77 ± 0.24 vs 1.69 ± 0.19 with p = 0.174) , female sex (24/77, 4% vs 45/73, 8%, p = 0.190) ,heart rate (FC) in bpm ( 71,90 ± 10,43 vs 70,36 ± 9,83), diastolic dimension of LV ( LVDD) em mm ( 46,71± 5,21 vs 46,05 ± 5,22) e ejection fracion of LV ( % por Teicholz) (73,55 ± 6,66 vs 73,56 ± 7,35). The prevalence of RV systolic dysfunction in normal patients and FIDC, using criteria such as FAC <35%, TAM <16mm and systolic S wave velocity <10 cm / s tissue Doppler was: FAC (- / 0.0% vs 1 / 0.6%, p = 0.663), TAM (- / 0.0% vs. - / 0.0%, p = 1.00) and S wave (2/6,4% vs 16/26% with p = 0.016) and a weak correlation (r = 0.31) between age and S wave (p = 0.019). The prevalence of RV global dysfunction in normal patients and FIDC : RIPM of TD(5/16,1% vs 17/27,8% , p=0,099) and RIPM of DP(19/61,3% vs 42/68,8%,p 0,141).The prevalence of RV diastolic dysfunction in groups I and II respectively, according to the criteria established by guideline43: abnormal relaxation AR (- / 0.0% vs 4/ 6.0%, p = 0.187), pseudonormal pattern PP (-/0,0 vs. -/0,0% p = 1,00) and restrictive pattern PR (-/0,0% vs -/0,0%, p = 1,000), with no significant difference in diastolic dysfunction in both groups. Conclusion: The prevalence of RV systolic dysfunction was estimated at 26% (S-wave velocity compared to other variables with p significant, with a weak correlation between the S wave velocity and age) and was not observed statistically significant criteria for diastolic dysfunction between groups. / Objetivo: Avaliar a prevalência de disfunção sistólica e diastólica do Ventrículo Direito (VD) em pacientes com forma indeterminada da doença de Chagas (FIDC) e comparar com pacientes assintomáticos sem esta patologia. Métodos: Estudo observacional, caso-controle, descritivo e de prevalência, na qual 91 pacientes foram divididos em dois grupos: grupo I (normal com n = 31) e grupo II (FIDC/normalidade cardíaca n = 61). Foram realizados nos pacientes adultos Dopplerecocardiograma 2D, aplicando os critérios de avaliação da função sistólica e diastólica do VD. Resultados: As características gerais de ambos grupos foram : idade (39,73 ± 12,94 vs 45,32 ± 12,36 com p = 0,071), peso em Kg (71,29 ± 14,91 vs 67,66 ± 12,37 com p = 0,270), altura em cm (159,24 ± 32,63 vs 156,88 ± 30,56 com p = 0,749), índice de superfície corpórea (ISC) (1,77 ± 0,24 vs 1,69 ± 0,19 com p = 0,174), sexo feminino (24/77,4% vs 45/73,8% com p = 0,190), frequência cardíaca (FC) em bpm ( 71,90 ± 10,43 vs 70,36 ± 9,83), dimensão diastólica do VE ( DDVE) em mm ( 46,71± 5,21 vs 46,05 ± 5,22) e fração de ejeção do VE ( % por Teicholz) (73,55 ± 6,66 vs 73,56 ± 7,35). A prevalência da disfunção sistólica do VD em pacientes normais e FIDC, utilizando critérios como Mudança de Área Fracional (MAF) < 35%, Mobilidade do Anel Tricuspídeo (MAT) < 16mm e velocidade da onda sistólica ao Doppler tecidual (ondaS) < 10 cm/s foi: MAF (- /0,0% vs 1/0.6% com p = 0,663), MAT (- / 0,0% vs - / 0,0% com p = 1,00) e onda S (2/6,4% vs 16/26,0% com p = 0.016). Houve fraca correlação (r = 0,31) entre a idade e a onda S (p = 0,019). A prevalência da disfunção global do VD no grupo I e II respectivamente foi: Índice de Performance Miocárdica Direita do Doppler Tecidual IPMD do DT (5/16,1% vs 17/27,8% com p =0,099) e IPMD do Doppler Pulsado DP:(19/61,3% vs 42/68% com p= 0,141), sem diferença estatística significativa entre os grupos. A prevalência de disfunção diastólica do VD nos grupos I e II respectivamente, conforme os critérios estabelecidos pelas diretrizes 43: alteração do relaxamento AR (- / 0,0% vs 4 / 6,0%, p = 0,187), padrão pseudonormal PP (-/ 0,0% vs -/ 0,0%, p =1,00) e padrão restritivo PR (-/0,0% vs -/0,0%, p = 1,00), sem diferenças significativas de disfunção diastólica em ambos grupos. Conclusão: A prevalência de disfunção sistólica do VD foi estimada em 26% (velocidade da onda S em comparação a outras variáveis com p significante e fraca correlação entre a velocidade da onda S e idade) e não foram observados critérios estatisticamente significantes para disfunção diastólica e global entre os grupos.