Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.

BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.

Perfil clínico e hemodinâmico de pacientes consecutivos com estenose aórtica valvar estudados na era pré-implante transcateter valvar aórtico em instituição acadêmica. Análise comparativa da avaliação invasiva com a ecocardiográfica / Clinical and hemodynamic profile of consecutive patients with aortic valve stenosis studied in the pre-transcatheter aortic valve implantation era at an academic institution. Comparative analysis of invasive evaluation with echocardiography

Introdução: Face à melhor compreensão da fisiopatologia da estenose valvar aórtica, cresceu paralelamente a complexidade da avaliação de sua gravidade, persistindo relevante incerteza quanto à aplicabilidade dos métodos invasivos pelo cateterismo cardíaco e os não invasivos, com base em ecocardiografia. O objetivo deste estudo foi analisar os padrões hemodinâmicos da avaliação com ecocardiografia comparativamente à estimativa da gravidade da estenose aórtica com o cateterismo em pacientes consecutivos referidos para avaliação diagnóstica por laboratório de hospital acadêmico terciário no triênio 2016-2018. Métodos: Estudo observacional, descritivo e retrospectivo das características clínicas e dos resultados das avaliações da gravidade da estenose valvar aórtica obtidas em 96 pacientes consecutivos, por meio de cateterismo e ecocardiografia. Resultados: Amostra populacional de 49 homens e 47 mulheres, com mediana de idade de 66,5 (56,5 a 72,8) anos, estenose valvar aórtica degenerativa em 49% e reumática em 40%, além de diversas comorbidades, inclusive doença coronária (37%). Pelo cateterismo, com base no gradiente pico de 48 (20 a 68), a estenose valvar aórtica foi avaliada como grave em 56%, sendo a pressão telediastólica ventricular de 20mmHg (16 a 30mmHg). Pela ecocardiografia, a área valvar foi 0,9cm2 (0,7 a 1,2cm2), sendo indexado 0,5cm2/m2 (0,43 a 0,5cm2/m2), com gradiente pico de 62±26 mmHg. A estenose valvar aórtica foi considerada severa em 69,2%. Houve discordância entre os métodos sobre a severidade da estenose valvar aórtica em 30% dos exames, com coeficiente de Spearman entre área valvar pelo ecocardiograma e gradiente pico pelo cateterismo de -0,7 (p<0,001). Conclusão: Em amostra representativa dos vários padrões hemodinâmicos, a avaliação da gravidade da estenose valvar aórtica, como praticada rotineiramente em laboratório acadêmico, limitou-se à medida de pico de gradiente transvalvar. A estimativa da área valvar pelo método ecocardiográfico, sendo indireta e também passível de crítica, contribui para as discrepâncias encontradas, tornando-se justificável buscar o aperfeiçoamento de ambos os métodos, em vista da complexidade clínica e hemodinâmica detectada.

Background: In view of the better understanding of the pathophysiology of aortic valve stenosis, the complexity of assessing its severity has simultaneously grown, with relevant uncertainty persisting as to the applicability of invasive methods by cardiac catheterization and non-invasive methods based on echocardiography. The objective of this study was to analyze the hemodynamic patterns of evaluation with echocardiography compared to the estimation of severity of aortic stenosis with catheterization in consecutive patients referred for diagnostic evaluation by the laboratory of a tertiary academic hospital in the 2016 to 2018 triennium. Methods: An observational, descriptive and retrospective study of clinical characteristics and results of assessments of severity of aortic valve stenosis obtained in 96 consecutive patients, through catheterization and echocardiography. Results: A population sample of 49 men and 47 women, with a median age of 66.5 (56.5 to 72.8) years, degenerative aortic valve stenosis in 49%, and rheumatic aortic stenosis in 40%, in addition to several comorbidities, including coronary disease (37%). Using catheterization, based on the peak gradient of 48 (20 to 68), aortic valve stenosis was assessed as severe in 56%, with ventricular end-diastolic pressure of 20mmHg (16 to 30mmHg). Using echocardiography, the valve area was 0.9cm2 (0.7 to 1.2cm2), indexed valve area was 0.5cm2/m2 (0.43 to 0.5cm2/m2), with peak gradient of 62±26mmHg. Aortic valve stenosis was considered severe in 69.2%. There was disagreement between the methods regarding severity of aortic valve stenosis in 30% of exams, with a Spearman coefficient between the valve area on the echocardiogram and the peak gradient on catheterization of -0.7 (p<0.001). Conclusion: In a representative sample of various hemodynamic patterns, the assessment of severity of aortic valve stenosis, as routinely practiced in an academic laboratory, was limited to measuring the peak transvalvular gradient. The estimation of the valve area using the echocardiographic method was indirect and also subject to criticism, and contributed to the discrepancies found, rendering it justifiable to seek the improvement of both methods, in view of the clinical and hemodynamic complexity detected.

Ocupação apical por endomiocardiofibrose associada a trombo diagnosticada com ecocardiografia de contraste e resolvida com tratamento clínico / Apical occupation by endomyocardiofibrosis associated with thrombus diagnosed with contrast echocardiography and resolved with clinical treatment

A endomiocardiofibrose é uma doença negligenciada e predominante em países subdesenvolvidos. Apesar de sua frequência, ainda é considerada rara. Assim, a doença é marcada pelos seguintes achados: distorção arquitetural, alterações no enchimento ventricular e alterações da mobilidade segmentar. Ela afetando não só a dinâmica diastólica e sistólica, como também as funções das válvulas cardíacas. Em uma condição mais avançada da doença, pode haver formação de trombos apicais. Neste relato de caso, revisitamos a endomiocardiofibrose, apresentando um caso desafiador de paciente do sexo feminino de 52 anos, com clínica de insuficiência cardíaca classe funcional IV da New York Heart Association. A eletrocardiografia de repouso revelou ritmo sinusal com sobrecarga do ventrículo esquerdo com vetores de alta voltagem, infradesnivelamento retificado do segmento ST e onda T negativa em região anterolateral, podendo ser compatível com padrão de strain. Já na avaliação de imagens ecocardiográficas, revelou dilatação acentuada do átrio esquerdo, com ventrículos sem dilatações e imagem de ocupação apical hiperrefringente no interior do ventrículo esquerdo, sugerindo grande trombo séssil sobreposto à capa fibrosa endocárdica. Embora a conduta cirúrgica seja a mais apoiada em literatura em tais situações, a paciente aqui apresentada recebeu tratamento com anticoagulação oral por 1 mês e 24 dias. Ela evoluiu clinicamente bem, com melhora da classe funcional da New York Heart Association e, em ecocardiografia realizada 2 meses após o início da anticoagulação oral, houve demonstração da regressão da imagem de trombo apical, apoiada com a técnica de contraste endocavitário.(AU)

Endomyocardial fibrosis (EMF) is a neglected but prevalent disease in underdeveloped countries. Despite its frequency, it is still considered a rare disease. It is marked by the following findings: architectural distortion, ventricular filling changes, and segmental mobility changes affecting not only diastolic and systolic dynamics but also heart valve function. Apical thrombi can be formed in more advanced disease. In this case report, we revisit EMF and present the challenging case of a 52-year-old woman with New York Heart Association (NYHA) functional classification (FC) IV heart failure. Resting electrocardiography revealed sinus rhythm with left ventricular (LV) overload, high voltage vectors, rectified ST-segment depression, and a negative T-wave in the anterolateral region compatible with the strain pattern. The evaluation of echocardiographic images showed marked left atrial dilation, no ventricular dilatation, and hyper-refringent apical occupation within the LV suggestive of a large sessile thrombus superimposed on the endocardial fibrous layer. Although surgery is the most supported approach in the literature in such situations, this patient was treated with oral anticoagulants (OAC) for 1 month and 24 days. The patient progressed well with an improved NYHA FC. Endocavitary contrast echocardiography performed 2 months after OAC initiation showed regression of the apical thrombus image. (AU)

Perfil de Prescrição de Estatinas e de Níveis Lipêmicos em Ambulatórios de Hospital Terciário Público / Statins Prescriptions and Lipid Levels in a Tertiary Public Hospital

Resumo Fundamento: O surgimento de nova classe de medicamentos com elevada capacidade de reduzir o LDL-colesterol (LDL-c) renovou o interesse na caracterização da hipercolesterolemia familiar (HF). Pouco se conhece do perfil lipídico de pacientes em atendimento terciário em nosso meio para caracterizar a real ocorrência de HF, que começa a ser suspeitada com níveis de LDL-c acima de 190mg/dL. Objetivos: O estudo avaliou o perfil lipídico (colesterol total [CT] e LDL-c) de pacientes de hospital público terciário. Métodos: Estudo retrospectivo de avaliação de prescrições de estatinas e resultados dos lipídios. O nível de significância foi estabelecido em 5%. Resultados: Em 1 ano, 9.594 indivíduos receberam prescrição ambulatorial de estatinas, 51,5% do gênero feminino, idade média de 63,7±12,9 anos (18 a 100 anos). Trinta e duas especialidades prescreveram estatinas, sendo a cardiologia responsável por 43%. Cerca de 15% das prescrições não tinham dosagem recente de CT, e 1.746 (18,0%) não apresentavam resultado recente de LDL-c. A ocorrência de LDL-c > 130mg/dL e < 190mg/dL ocorreu em 1.643 (17,1%) casos, e 228 (2,4%) apresentaram LDL-c ≥ 190mg/dL dentre os que utilizavam estatinas nas diversas doses. Apenas duas estatinas foram utilizadas: sinvastatina e atorvastatina, e a primeira foi prescrita em 77,6% das receitas. Conclusão: Nesta coorte transversal de hospital terciário, foi possível verificar que a prescrição de estatinas é disseminada, mas que a obtenção de metas adequadas de CT e LDL-c não é atingida em grande percentual, e que há, possivelmente, significativo contingente de portadores de HF que necessitariam ser investigados por suas implicações prognósticas.

Abstract Background: The development of a new class of medications that are highly capable of reducing LDL-cholesterol renewed the interest in the characterization of familial hypercholesterolemia patients. Nevertheless, little is known about the lipid profile of patients in tertiary healthcare centers in Brazil in order to better estimate the real occurrence of familial hypercholesterolemia, with initial suspect of LDL-cholesterol levels above 190 mg/d/L. Objectives: This study evaluated the lipid profile (total cholesterol and LDL-cholesterol) in ambulatory patients from a general tertiary public hospital. Methods: Retrospective study comparing prescriptions of statins and lipid profile results. The significance level was established in 5%. Results: In one year, 9,594 individuals received statin prescriptions, of whom 51.5% were females and the mean age was 63.7±12.9 years-old (18 to 100 years-old). Thirty-two medical specialties prescribed statins. Cardiology was responsible for 43% of the total. Nearly 15% of those patients with a prescription did not have a recent total cholesterol result and 1,746 (18%) did not have a recent LDL-cholesterol measurement. The occurrence of the latter between 130 and 190 mg/dL was present in 1,643 (17.1%) individuals, and 228 (2.4%) patients had an LDL-cholesterol ≥190mg/dL among those using statins at distinct doses. Only two statins were used: simvastatin and atorvastatin. The first was prescribed in 77.6% of the prescriptions. Conclusion: In this cross-sectional cohort at a tertiary general hospital, statins have been widely prescribed but with little success in achieving recognized levels of control. There is probably a significant number of FH individuals in this cohort that need to be properly diagnosed in order to receive adequate treatment due to its prognostic implications.

Análise do processo de manutenção e de vida útil dos equipamentos médicos ecocardiógrafos: a experiência de um hospital de ensino / Analysis of the maintenance process and useful life of echocardiography equipment: An experience in a teaching hospital

Introdução: A ecocardiografia é uma ferramenta diagnóstica de crescente utilização na prática clínica, aplicada a diversos cenários médicos. Os cuidados e os processos de manutenção preventiva ou corretiva dos equipamentos são ainda pouco padronizados. O objetivo do presente estudo foi descrever o processo de manutenção atualmente aplicado a equipamentos ecocardiográficos em um laboratório. Descrever o processo inclui a caracterização de danos e aplicações de manutenção preventiva ou corretiva. Métodos: Estudo observacional descritivo e exploratório realizado em centro único. As informações de dados do processo de manutenção de equipamentos ecocardiográficos foram obtidas de arquivos eletrônicos do sistema de gestão de equipamentos de um laboratório de médio porte de um hospital público de nível terciário com características de ensino, no período de 2003 a 2018. Resultados: Foram identificados dez tipos de avarias mais comuns, como dano a programas (23,8%), peças (23,1%) e relacionadas à queda de energia e de acessórios (13,8%). Após a implementação do processo de manutenção preventiva, houve significativa redução dos custos de manutenções (US$ 44.472,10 versus US$ 25.807,59; p= 0,029). Mesmo após a manutenção preventiva, os custos de manutenção corretiva em equipamentos aplicados à ecocardiografia transesofágica (US$ 7.789,17) foram maiores que aqueles a equipamentos aplicados a outras modalidades (US$ 3.184,37 em ecocardiografia transtorácica e US$1.813,00 em estresse). Conclusão: O processo de manutenção de equipamentos ecocardiográficos foi descrito. Danos a equipamentos ecocardiográficos estão relacionados a altos custos, principalmente naqueles aplicados a modalidades especiais, como ecocardiografia transesofágica. As manutenções preventivas reduziram significativamente os custos de manutenção. (AU)

Introduction: Echocardiography is a diagnostic tool that is increasingly used in clinical practice in different medical scenarios; however, the preventive (PM) or corrective maintenance (CM) care and processes for this equipment are still poorly standardized. To describe the maintenance process currently implemented for echocardiographic equipment (ECHO) in a medium-sized laboratory in a tertiary-level public teaching hospital. The description of the process includes damage characterization and MP and MC implementation. Methods: This was a descriptive and exploratory single-center observational study. Data on the maintenance process of echocardiographic equipment were obtained from electronic files from the hospital's equipment management system between 2003 and 2018. Results: Together with the description of the equipment maintenance process, the ten most common types of malfunctions were identified, including software (23.8%), parts (23.1%), and power outage and accessory damage (13.8%). The implementation of the PM process significantly decreased the maintenance costs (USD 44,472.10 vs USD 25,807.59, p = 0.029). Even after the MP, the CM costs related to transesophageal echocardiography equipment (TEE) (USD 7,789.17) were higher than those with other equipment modalities (USD 3,184.37 for transthoracic echocardiography equipment (TTE) and USD 1,813.00 for stress testing). Conclusion: The maintenance process for ECHO equipment was described. ECHO equipment damage has high costs, especially in special modalities such as TEE. PM significantly reduced maintenance costs. (AU)

Cardiac Alterations in Patients with Familial Lipodystrophy.

Familial lipodystrophy is a rare genetic condition in which individuals have, besides metabolic changes and body fat deposits, a type of cardiomyopathy that has not been well studied. Many of the patients develop cardiovascular changes, the most commonly reported in the literature being the expression of a type of hypertrophic cardiomyopathy. This article, presented as a bibliographic review, reviews the clinical and cardiovascular imaging aspects in this scenario of cardiomyopathy in a rare metabolic disease, based on the latest scientific evidence published in the area. Despite the frequent association of congenital lipodystrophy and ventricular hypertrophy described in the literature, the pathophysiological mechanisms of this cardiomyopathy have not yet been definitively elucidated, and new information on cardiac morphological aspects is emerging in the aegis of recent and advanced imaging methods, such as cardiac magnetic resonance.

Cardiac Alterations in Patients with Familial Lipodystrophy / Alterações Cardiovasculares em Pacientes Portadores de Lipodistrofia Familiar

Abstract Familial lipodystrophy is a rare genetic condition in which individuals have, besides metabolic changes and body fat deposits, a type of cardiomyopathy that has not been well studied. Many of the patients develop cardiovascular changes, the most commonly reported in the literature being the expression of a type of hypertrophic cardiomyopathy. This article, presented as a bibliographic review, reviews the clinical and cardiovascular imaging aspects in this scenario of cardiomyopathy in a rare metabolic disease, based on the latest scientific evidence published in the area. Despite the frequent association of congenital lipodystrophy and ventricular hypertrophy described in the literature, the pathophysiological mechanisms of this cardiomyopathy have not yet been definitively elucidated, and new information on cardiac morphological aspects is emerging in the aegis of recent and advanced imaging methods, such as cardiac magnetic resonance.

Resumo A lipodistrofia familiar é uma condição genética rara na qual indivíduos apresentam, além das alterações metabólicas e de depósitos de gordura físicos, um tipo de cardiomiopatia pouco estudada. Muitos dos pacientes desenvolvem alterações cardiovasculares, sendo a mais comumente reportada em literatura, a expressão de um tipo de cardiomiopatia hipertrófica. Este artigo, apresentado como uma revisão bibliográfica, revisa os aspectos clínicos e de imagem cardiovascular neste cenário de cardiomiopatia em doença metabólica rara, com base nas últimas evidências científicas publicadas na área. Apesar da frequente associação de lipodistrofia congênita e hipertrofia ventricular descrita em literatura, os mecanismos fisiopatológicos desta cardiomiopatia ainda não estão definitivamente elucidados, e novas informações do aspecto morfológico cardíaco surgem à égide de recentes e avançados métodos de imagem como a ressonância cardíaca magnética.

Prolonged dipyridamole administration reduces myocardial perfusion defects in experimental chronic Chagas cardiomyopathy.

BACKGROUND: Myocardial perfusion defects (MPD) due to coronary microvascular dysfunction is frequent in chronic Chagas cardiomyopathy (CCC) and may be involved with development of myocardial damage. We investigated whether MPD precedes left ventricular systolic dysfunction and tested the hypothesis that prolonged use of dipyridamole (DIPY) could reduce MPD in an experimental model of CCC in hamsters. METHODS AND RESULTS: We investigated female hamsters 6-months after T. cruzi infection (baseline condition) and control animals, divided into T. cruzi-infected animals treated with DIPY (CH + DIPY) or placebo (CH + PLB); and uninfected animals treated with DIPY (CO + DIPY) or placebo (CO + PLB). The animals were submitted to echocardiogram and rest SPECT-Sestamibi-Tc99m myocardial perfusion scintigraphy. Next, the animals were treated with DIPY (4 mg/kg bid, intraperitoneal) or saline for 30 days, and reevaluated with the same imaging methods. At baseline, the CH + PLB and CH + DIPY groups showed larger areas of perfusion defect (13.2 ± 13.2% and 17.3 ± 13.2%, respectively) compared with CO + PLB and CO + DIPY (3.8 ± 2.2% e 3.5 ± 2.7%, respectively), P < .05. After treatment, we observed: reduction of perfusion defects only in the CH + DIPY group (17.3 ± 13.2% to 6.8 ± 7.6%, P = .001) and reduction of LVEF in CH + DIPY and CH + PLB groups (from 65.3 ± 9.0% to 53.6 ± 6.9% and from 69.3 ± 5.0% to 54.4 ± 8.6%, respectively, P < .001). Quantitative histology revealed greater extents of inflammation and interstitial fibrosis in both Chagas groups, compared with control group (P < .001), but no difference between Chagas groups (P > .05). CONCLUSIONS: The prolonged use of DIPY in this experimental model of CCC has reduced the rest myocardial perfusion defects, supporting the notion that those areas correspond to viable hypoperfused myocardium.

Short-term and long-term models of doxorubicin-induced cardiomyopathy in rats: A comparison of functional and histopathological changes.

OBJECTIVES: Doxorubicin (DXR), an anthracyclic antineoplastic agent, is one of the most commonly drug utilized to induce dilated cardiomyopathy (DCM) and heart failure (HF), but the well optimized protocol for cardiomyopathy induction leading to development of cardiac systolic dysfunction is unclear. This study aims to critically compare short-term and long-term DXR injection protocols for the induction of DCM in rats. METHODS: Animals were allocated into 3 experimental groups: a ST (short-term DXR injection) group, in which animals received 6 intraperitoneal (i.p.) injections of DXR (2.5mg/kg per dose) over a period of 2 weeks (cumulative dose of 15mg/kg); a LT (long-term DXR injection) group in which animals received weekly i.p. injections of DXR (2mg/kg per dose) over a period of 9 weeks (cumulative dose of 18mg/kg); and a control group in which animals received an appropriate volume of 0.9% saline i.p. All animals were submitted to echocardiography analysis at baseline and after completion treatment. Afterwards, the hearts were collected for conventional light microscopy and collagen quantification. RESULTS: Morphological myocardial analysis of both DXR-treated groups showed an identical pattern of swollen and vacuolated cardiomyocytes and disorganization of myofibrils. There was pronounced interstitial fibrosis in both groups of DXR-treated hearts as compared to controls, as assessed by the interstitial collagen volume fraction. There was no difference in interstitial fibrosis between the ST and LT groups. The echocardiography analysis of the LT group showed structural and functional findings compatible with DCM, including increased left ventricular systolic (5.02±0.96mm) and diastolic (7.68±0.96mm) dimensions and reduction of ejection fraction (69.40±8.51%) as compared to the ST group (4.10±0.89mm, 7.32±0.84, and 79.68±7.23%, respectively) and control group (4.07±0.72mm, 7.17±0.68mm and 80.08±4.71%, respectively), ANOVA p<0.01. CONCLUSIONS: These results indicate that LT injection of DXR is more effective than ST injection in inducing left ventricular dysfunction and structural cardiac changes resembling those found in dilated cardiomyopathy.

Comparison between Radionuclide Ventriculography and Echocardiography for Quantification of Left Ventricular Systolic Function in Rats Exposed to Doxorubicin.

BACKGROUND: Radionuclide ventriculography (RV) is a validated method to evaluate the left ventricular systolic function (LVSF) in small rodents. However, no prior study has compared the results of RV with those obtained by other imaging methods in this context. OBJECTIVES: To compare the results of LVSF obtained by RV and echocardiography (ECHO) in an experimental model of cardiotoxicity due to doxorubicin (DXR) in rats. METHODS: Adult male Wistar rats serving as controls (n = 7) or receiving DXR (n = 22) in accumulated doses of 8, 12, and 16 mg/kg were evaluated with ECHO performed with a Sonos 5500 Philips equipment (12-MHz transducer) and RV obtained with an Orbiter-Siemens gamma camera using a pinhole collimator with a 4-mm aperture. Histopathological quantification of myocardial fibrosis was performed after euthanasia. RESULTS: The control animals showed comparable results in the LVSF analysis obtained with ECHO and RV (83.5 ± 5% and 82.8 ± 2.8%, respectively, p > 0.05). The animals that received DXR presented lower LVSF values when compared with controls (p < 0.05); however, the LVSF values obtained by RV (60.6 ± 12.5%) were lower than those obtained by ECHO (71.8 ± 10.1%, p = 0.0004) in this group. An analysis of the correlation between the LVSF and myocardial fibrosis showed a moderate correlation when the LVSF was assessed by ECHO (r = -0.69, p = 0.0002) and a stronger correlation when it was assessed by RV (r = -0.79, p < 0.0001). On multiple regression analysis, only RV correlated independently with myocardial fibrosis. CONCLUSION: RV is an alternative method to assess the left ventricular function in small rodents in vivo. When compared with ECHO, RV showed a better correlation with the degree of myocardial injury in a model of DXR-induced cardiotoxicity.

Comparison between Radionuclide Ventriculography and Echocardiography for Quantification of Left Ventricular Systolic Function in Rats Exposed to Doxorubicin / Comparação entre a Ventriculografia Radioisotópica e a Ecocardiografia na Quantificação da Função Sistólica Ventricular Esquerda em Ratos Expostos à Doxorrubicina

Abstract Background: Radionuclide ventriculography (RV) is a validated method to evaluate the left ventricular systolic function (LVSF) in small rodents. However, no prior study has compared the results of RV with those obtained by other imaging methods in this context. Objectives: To compare the results of LVSF obtained by RV and echocardiography (ECHO) in an experimental model of cardiotoxicity due to doxorubicin (DXR) in rats. Methods: Adult male Wistar rats serving as controls (n = 7) or receiving DXR (n = 22) in accumulated doses of 8, 12, and 16 mg/kg were evaluated with ECHO performed with a Sonos 5500 Philips equipment (12-MHz transducer) and RV obtained with an Orbiter-Siemens gamma camera using a pinhole collimator with a 4-mm aperture. Histopathological quantification of myocardial fibrosis was performed after euthanasia. Results: The control animals showed comparable results in the LVSF analysis obtained with ECHO and RV (83.5 ± 5% and 82.8 ± 2.8%, respectively, p > 0.05). The animals that received DXR presented lower LVSF values when compared with controls (p < 0.05); however, the LVSF values obtained by RV (60.6 ± 12.5%) were lower than those obtained by ECHO (71.8 ± 10.1%, p = 0.0004) in this group. An analysis of the correlation between the LVSF and myocardial fibrosis showed a moderate correlation when the LVSF was assessed by ECHO (r = -0.69, p = 0.0002) and a stronger correlation when it was assessed by RV (r = -0.79, p < 0.0001). On multiple regression analysis, only RV correlated independently with myocardial fibrosis. Conclusion: RV is an alternative method to assess the left ventricular function in small rodents in vivo. When compared with ECHO, RV showed a better correlation with the degree of myocardial injury in a model of DXR-induced cardiotoxicity.

Resumo Fundamento: A ventriculografia radioisotópica (VRI) é um método validado para avaliação da função sistólica do ventrículo esquerdo (FSVE) em pequenos roedores. Contudo, nenhum estudo prévio comparou os resultados obtidos com VRI com os obtidos por outros métodos de imagem neste contexto. Objetivos: Comparar os resultados de FSVE obtidos por VRI e por ecocardiografia (ECO) em modelo experimental de cardiotoxicidade por doxorrubicina (DXR) em ratos. Métodos: Ratos Wistar machos adultos controles (n = 7) e tratados com DXR (n = 22) em doses acumuladas de 8, 12 e 16 mg/kg, foram avaliados com ECO com equipamento Sonos 5500 Philips (transdutor de 12 MHz) e VRI adquirida em gama-câmara Orbiter-Siemens com colimador pinhole de 4 mm de abertura. Após eutanásia, foi realizada a quantificação histopatológica da fibrose miocárdica. Resultados: Os animais controles apresentaram valores comparáveis na análise da FSVE à ECO e à VRI (83,5 ± 5% e 82,8 ± 2,8%, respectivamente, p > 0,05). Os animais que receberam DXR apresentaram valores menores de FSVE quando comparados aos dos controles (p < 0,05); entretanto, observou-se neste grupo menores valores de FSVE obtidos por VRI (60,6 ± 12,5%) quando comparados aos obtidos pela ECO (71,8 ± 10,1%, p = 0,0004). A análise da correlação entre a FSVE e a fibrose miocárdica mostrou uma correlação moderada quando a FSVE foi estimada com a ECO (r = -0,69, p = 0,0002) e mais forte quando a FSVE foi obtida por VRI (r = -0,79, p < 0,0001). Apenas a VRI apresentou correlação de forma independente com a fibrose miocárdica à análise de regressão múltipla. Conclusão: A VRI é um método alternativo para avaliação da função ventricular esquerda in vivo em pequenos roedores, exibindo comparativamente à ECO melhor correlação com o grau de lesão miocárdica no modelo de cardiotoxicidade por DXR.