The Effect of Alloxan-Induced Hyperglycemia on the Myocardium of Experimental Animals
Diabetes mellitus is a current problem because the number of deaths from its complications is more than the total number of people who died of AIDS, tuberculosis and malaria. Nowadays the most widespread experimental model of diabetes mellitus is the chemical. As inducers of diabetes, streptozotocin is used in 69% of experimental studies and alloxan - in 31%. The dose and route of alloxan administration, duration and severity of diabetes induced by alloxan is discutable. The aim of our study was the evaluation of effectiveness of the animal model of alloxan-induced hyperglycemia and determination the features of heart remodelling in rats of different age.
Matherial and Method: The experiment was conducted on 28 laboratory male rats of two age groups: young (3 months old), and mature (8 months old). Modeling of alloxan hyperglycemia performed by injection of alloxan, pre-dissolved in 0.9% solution of sodium chloride, intraperitoneally once at a dose of 170 mg/kg on an empty stomach. The animals additionally received a 10% glucose solution during 24 hours after alloxan administration and 5% glucose solution during the experiment. The glucose level was measured with Accu-Chek Advantage (Boehringer, Germany) after 2, 12 and 24 hours after alloxan injection, and then weekly. The average level of glucose in the blood remained at 11 mmol / L ± 2 mmol / L. The experiment lasted 45 days. We analysed hearts remodeling by organometry and light microscopy.
Results: The mortality of 3 months old rats was 12.5%, and 8 months old rats mortality was 25%. The organometric study indicated the weight increase of both venrtricles, which was more pronounced in 8-month old rats. Also we revealed the dilation of left ventricle in young rats and dilation of both ventricles in mature ones. Light microscopy showed microcirculation disorders, polymorphismus of cardiomyocytes nuclei, the phenomenon of cytolysis, desorientation, wavy deformation and fragmentation of cardiomyocytes fibers, swollowing of myocardial stroma, and local fibrosis with focal cell infiltration.
Conclusions: The obtained results suggest that alloxan can be used for further experiments on laboratory animals with the aim of modeling the diabetes mellitus type 1 and finding ways to correct the detected changes. The features of myocardial remodeling under the influence of alloxan-induced hyperglycemia are the tendency for hypertrophy and ventricular dilatation, disturbance of myocardial microcirculation, its contractile dysfunction and local fibrosis.