Study of the Possible Cardioprotective Effects of Erythropoietin in Diabetic and Uremic Cardiomyopathy in Rats
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- Category: Vol. 85, March 2017
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Study of the Possible Cardioprotective Effects of Erythropoietin in Diabetic and Uremic Cardiomyopathy in Rats, HANIA I. AMMAR, AYMAN S. SOLIMAN, MUHAMMED A. EASHRA and HEBA A. HASHEM
Abstract
Introduction: Cardiomyopathy is a common chronic complication associated with diabetes and chronic kidney disease. Erythropoietin (EPO) was reported as a broad spectrum cardioprotective agent.
Aim of Work: In this study, we aim to compare between the ability of EPO to exert its beneficial role as cardioprotective agent in two different models of cardiomyopathy; diabetic and uremic cardiomyopathy.
Material and Methods: This study was applied on 48 male albino rats that were divided into 6 equal groups: Control group, diabetic group, diabetic + (EPO) group, nephrectomy group, (neph + EPO) group and sham operation group. The study proceeded for 12 weeks for diabetic model and for 16 weeks for uremic model. Diabetes was induced by Intraperi-toneal (IP) injection of 65mg/kg STZ. Uremia was induced by 5/6 subtotal nephrectomy. EPO treated groups were injected with 1000IU/kg of EPO (IP) twice weekly till the end of the study. Echocardiographic assessment was done at the 12th and 16th weeks for diabetic and uremic groups respectively also, heart tissues were collected for pathological examination.
Results: Echocardiographic assessment of cardiac function of uremic group showed that there was significant decrease in EF% & FS% by the 12th week in untreated nephrectomy group compared with their baseline value, EPO treated ne-phrectomy and sham operated group. Further decrease was observed at 16th week. However, in EPO treated nephrectomy group EPO maintained the EF% and FS% normal as there was no significant decrease compared with sham operated group up to the12th week. By the 16th week EF% of EPO treated nephrectomy group was significantly lower than sham group but still significantly higher than untreated group. In addition, echocardiographic assessment of cardiac function of diabetic group showed that there was significant decrease in EF% & FS% by the 4th week in both untreated and EPO treated diabetic groups compared to control group. Cardiac functions of both diabetic groups continued to decrease up to the end of the study (12th week). Pathological examination of both nephrectomy group by hematoxylin and eosin staining showed signs of cardiac muscle hypertrophy with more cardiac degeneration in untreated group. While in EPO treated group, there was increase in number of sprouting capillaries compared with untreated and sham groups which further proved with trichrome staining. Also, trichrome staining showed significant increase in the area percent of fibrosis in untreated nephrectomy group compared with both EPO treated and sham groups. Hematoxylin and eosin staining of the heart tissues of diabetic group there was no signs of cardiac hypertrophy. The cardiac muscles appear with signs of hyaline and fatty degeneration. There was apparent infiltration with fatty vacuoles inside and in between muscle fibers. The blood vessels appear dilated and some was congested with blood. The vessel walls also show excess vacuolation with perivascular edema.
Conclusion: Through these results we can observe that in uremic model EPO treatment succeeded in preserving the cardiac function and delaying the development of uremic cardiomyopathy and this might be due to limiting fibrosis or increasing capillary number with further improvement of cellular oxygenation. But these beneficial effects could not be exerted with the diabetic model and the state of insulin insufficiency. The matter that ensure that the underling systemic disease can differentially activate or inactivate the molecular signaling pathways of EPO.