Metabolic markers of myocardium insulin resistance in dogs with heart failure

Background: Heart failure syndrome is an aspect of primary or secondary heart disease and associated with decompensation, formation, and activation of pathological interactions between regulation systems. This results in myocardial energy metabolism alteration. This study performed to defy some metabolic aspects of myocardial tissue insulin resistance development in canine heart failure. Aim: Investigation of myocardial tissue concentration of ATP, glucose transporters 1 and 4, pyruvate dehydrogenase, hexokinase 2, insulin receptor, and adropin protein, to screen metabolic changes and insulin resistance in canine myocardium with heart failure. Methods: We studied 28 dogs of different sex, age, and breed. Groups were formed according to primary pathology: apparently healthy dogs (HD, n=6); dogs with CDVD (CDVDD, n=8); dogs with DCM (DCMD, n=6); dogs with doxorubicin chemotherapy (DoxCMD, n=8). Animals in the study were diagnosed for primary disease by standard methods and algorithms. Animals were euthanized due to uncurable neurological disease, refractory heart failure or by owners will. The material was obtained immediately after death, fixed in liquid nitrogen and stored in -80C refrigerator. Studied proteins concentrations were analyzed in a specialized research laboratory, using ELISA kits, provided by Cloud-Clone Corp. Results: ATP, GLUT1 and GLUT4 concentrations in myocardial tissue from valvular disease group did not differ from HD group. In CDVD we found depression of PDH, HX2, ADR concentrations in comparison to HD. InsR was significantly lower in CDVD and DoxCMD groups in comparison to HD, but in DCM group, it was twofold higher than in HD. In DCMD and DoxCMD groups all parameters were lower than in HD. ATP, HX2, ADR, GLUT1, GLUT4 were higher in CDVD group, than in DCM and DoxCM. PDH in CDVD and DoxCM group did not differ. PDH was depleted in DCM to CDVD and DoxCM. Insulin receptor did not differ between CDVD and DoxCM groups, but was upregulated in DCM to CDVD and DoxCM groups. Conclusion: Development of myocardial tissue insulin resistance is a part of structural, functional and metabolic remodeling in dogs with heart failure of different etiology. At the late stages, we found significant changes in energy supply availability and production in the myocardium