Correlation between systolic function and presence of myofibroblasts in doxorubicin-induced cardiomyopathy / Correlação entre função sistólica e presença de miofibroblastos na cardiomiopatia induzida pela doxorrubicina

ABSTRACT: Cardiotoxicity induced by doroxubicin generates systolic disfunction and myocardial remodeling with presence of myofibroblasts. These cells are thought to be attracted to the injured heart to avoid the development of congestive heart failure. The objective of this study was to evaluate the systolic dysfunction generated by doxorubicin through Doppler echocardiography, and its correlation with the presence of myofibroblasts in the myocardium. Twenty-five New Zealand White rabbits were divided into two groups (control, and treated with doxorubicin). The drug was administered for six weeks; Doppler echocardiography was performed before the first, and after the last administration of doxorubicin. Immuno detection of myofibroblasts was performed by immunohistochemistry. The treated group exhibited significant reduction in systolic function as assessed by Doppler echocardiography, and increased frequency of myofibroblasts, which were present in similar amounts in the left ventricle, interventricular septum, and right ventricle. There was a significant negative correlation between number of myofibroblasts in the interventricular septum and in the left ventricle with systolic function indices, which reveals that the higher the number of fibroblasts, the worst systolic function is in rabbits treated with doxorubicin. Increase in myofibroblast numbers was not sufficient to preserve systolic function.

RESUMO: A cardiotoxicidade induzida pela doxorrubicina gera disfunção sistólica e remodelamento miocárdico, com presença de miofibroblastos. Acredita-se que essas células sejam atraídas para a não evolução do quadro de insuficiência cardíaca congestiva. O objetivo do presente trabalho foi avaliar a função sistólica gerada pela doxorrubicina por meio da ecodopplercadiografia e correlacioná-la com a presença de miofibroblastos no miocárdio. Foram utilizados 25 coelhos da raça Nova Zelândia, alocados em dois grupos (controle e tratados com doxorrubicina). O fármaco foi administrado por seis semanas e a ecodopplercardiografia foi realizada no momento zero e após a última administração da doxorrubicina. A imunodetecção dos miofibroblastos foi realizada por imuno-histoquímica. Houve redução significativa na função sistólica, observada na ecodopplercardiografia e aumento na imundetecção dos miofibroblastos nos animais tratados, na mesma intensidade no ventrículo esquerdo, septo interventricular e ventrículo direito. Houve correlação negativa significativa entre o número de miofibroblastos no septo interventricular e no ventrículo esquerdo com os índices de função sistólica, revelando que quanto mais miofibroblastos presentes, pior é a função sistólica de coelhos tratados com doxorrubicina. O aumento do número de miofibroblastos não foi suficiente para manutenção da função sistólica.

Hypertension and its correlation with renal lesions in dogs with leishmaniosis.

To evaluate the prevalence of hypertension and its correlation with the severity of renal injury and proteinuria in dogs with leishmaniosis, sixty-six dogs were divided into two groups. Group 1 (G1) was composed of 54 dogs included in stage 1 of chronic kidney disease (CKD), and group 2 (G2) of twelve dogs in stages 2 and 3 of CKD. Prevalence of hypertension was 28.8%, comprising 22.2% of the dogs from G1 and 58.3% from G2 (P=0.011). The mean arterial blood pressure (BP) of dogs from G1 (135.7 ± 20.5) was lower than from G2 (170.0 ± 26.3) (P <0.001). Urine protein-creatinine ratio (UP/C) revealed values above 0.5 in 75.7% of the dogs, with 34% presenting hypertension. All dogs with hypertension had histopathological and laboratory evidence of glomerular disease. Although there was no statistically significant correlation between elevated BP and the severity of glomerular lesions (P=0.408), there was a statistically significant correlation between elevated BP and increased UP/C in the studied population (P=0.002). Thus, dogs with leishmaniosis and renal disease must be screened for the presence of hypertension so that treatment may be instituted as early as possible, in countries where treatment is allowed, to prevent the progression of renal damage.

Hypertension and its correlation with renal lesions in dogs with leishmaniosis / Hipertensão e sua correlação com lesões renais em cães com leishmaniose

To evaluate the prevalence of hypertension and its correlation with the severity of renal injury and proteinuria in dogs with leishmaniosis, sixty-six dogs were divided into two groups. Group 1 (G1) was composed of 54 dogs included in stage 1 of chronic kidney disease (CKD), and group 2 (G2) of twelve dogs in stages 2 and 3 of CKD. Prevalence of hypertension was 28.8%, comprising 22.2% of the dogs from G1 and 58.3% from G2 (P=0.011). The mean arterial blood pressure (BP) of dogs from G1 (135.7 ± 20.5) was lower than from G2 (170.0 ± 26.3) (P <0.001). Urine protein-creatinine ratio (UP/C) revealed values above 0.5 in 75.7% of the dogs, with 34% presenting hypertension. All dogs with hypertension had histopathological and laboratory evidence of glomerular disease. Although there was no statistically significant correlation between elevated BP and the severity of glomerular lesions (P=0.408), there was a statistically significant correlation between elevated BP and increased UP/C in the studied population (P=0.002). Thus, dogs with leishmaniosis and renal disease must be screened for the presence of hypertension so that treatment may be instituted as early as possible, in countries where treatment is allowed, to prevent the progression of renal damage.

Para avaliar a prevalência de hipertensão arterial e sua correlação com a severidade da lesão renal e proteinúria em cães com leishmaniose, 66 cães foram divididos em dois grupos. O grupo 1 (G1), composto por 54 cães em estágio 1 de doença renal crônica (DRC), e o grupo 2 (G2) por 12 cães em estágios 2 e 3 de DRC. A prevalência de hipertensão foi de 28,8%, compreendendo 22,2% dos cães de G1 e 58,3% dos cães de G2 (p = 0,011). A pressão arterial média (PA) de G1 (135,7 ± 20,5) foi inferior a de G2 (170,0 ± 26,3) (P <0,001). A relação proteína creatinina urinária (P/C U) foi maior que 0,5 em 75,7% dos cães, dos quais 34% possuíam hipertensão. Todos os cães com hipertensão apresentavam doença glomerular. Embora não tenha sido observada correlação estatisticamente significativa entre elevação da PA e severidade das lesões glomerulares (P =0,408), houve uma correlação significativa entre PA elevada e aumento da UP/C (P = 0,002). Portanto, cães com leishmaniose e doença renal devem ser pesquisados ​​quanto à presença de hipertensão, para que o tratamento possa ser instituído o mais precocemente possível em países onde ele é permitido, para evitar a progressão da lesão renal.