Morphological quantification of myocardial pathology in the Zucker diabetic fatty rat

Abstract Zucker Diabetic Fatty rat is an animal model that demonstrates disease progression in terms of complications which are similar to those seen in patients with Type 2 diabetes.The objective of the current study was to employ light and electron microscopy to quantify changes to the myocardial microvasculature and cardiomyocytes in the myocardial tissue of ZDF rats and establish a mechanistic basis for alterations in cardiac function. Materials and Methods:ZDF rats and lean Zucker rats (control) were housed in groups according to their breed. The ZDF rats were supplied with diabetogenic chow (Purina 5008) while the lean Zucker rats had access to standard chow as recommended by the supplier. At 12-14 weeks of age, animals were weighed and sacrificed by cervical dislocation. A blood sample was obtained for determination of blood glucose, and lipid profile.Both samples from LAA and the apex of left ventricle were carefully dissected, divided into small sections then fixed, impeded, sectioned, stained and random sections were photographed and the images were assessed and quantified using Image Analyser Pro-Plus software, version 4.1. Arterioles, venules, intermediate sized vessels, and capillaries were directly counted within the highlighted area of myocardium under light microscope. Ultra-thin sections were imaged in a Tecnai 12 Biotwin transmission electron microscope at a magnification of x4200 and photographed by a camera with a black and white film to quantify different structures of myocardium. Results: Significant reductions in the total vessel, intermediate vessel and capillary density of LAA in the ZDF rats compared to controls were noticed (P= 0.03). As well as a significant increase in the transverse diameter of cardiomyocytes in the ZDF rats compared to controls of LV (P= 0.049). There were significant increase in the basement membrane area of distal myocardial capillaries of both left atrium appendage and left ventricle in the ZDF rats compared to controls (P= 0.008). Conclusion: Early evidence of cardiomyocyte hypertrophy with a reduction in atrial vascular density and evidence of early structural changes in myocardial capillaries in the ZDF rats was noticed. These changes indicate the presence of microangiopathy in the heart of ZDF rats which is surprisingly more prominent in the LAA. Keywords: Zucker Diabetic Fatty (ZDF), Type 2 diabetes mellitus, Left Atrial Appendage, Left ventricle, Cardiomyocyte, Myocardial capillaries.