Metabolic Features of Heart Failure with Different Etiology

Abstract

Dilated Cardiomyopathy (DCM) and Chronical Degenerative Valvular Disease (CDVD) are very common in dogs nowadays. However, due to modern level in oncology we can meet chemotherapy-induced cardiomyopathies more often. We have lack of information about pathogenic mechanisms underlying Doxorubicin-induced Cardiomyopathy (DoxCM) and features differentiating it from CDVD and DCM. In this study we investigate several metabolic features of doxorubicin-induced cardiomyopathy, DCM-like phenotype cardiomyopathies and CDVD. We observed some stages of myocardium glucose metabolism in order to estimate life potential of end stage myocardium and respectively survival of patient. The study population consisted of 46 dogs of different age, sex and breed. These dogs were subgrouped due to diagnosis: Healthy dogs without heart failure, DCM, CDVD and DoxCM. Fresh myocardial biopsies taken immediately after euthanasia from left ventricular apex, freezed in liquid nitrogen for ELISA and biochemical study. Differences in metabolic profile found between of CDVD and healthy dogs were not significant. At the same time doxorubicin induced cardiomyopathy and DCM-like phenotype myocardial disease had similar changes. It should be mentioned, DCM patients had previously long history of treatment, but DoxCM group-not. Differences between DoxCM, DCM and CDVD were significant and can be explained by changes what suffering myocardium undergoes. Rapid or slow developing energy depletion leads to myocardiocytes death and heart failure. Doxorubicin-induced cardiomyopathy is far more dangerous due to rapidness of development in observed study. Myocardium, due to lack of time, had no adapting ability for acute energy depletion and massive cell death. This preliminary study shows changes induced by doxorubicin (Dox) in dogs. These findings mostly connected with mitochondrial disturbances, insulin resistance and energy depletion. In this study also shown several features connected with development of CDVD and differences from DCM.

Metabolic Markers of Insulin Resistance in Feline Hypertrophied Myocardium. Insulin Resistance in Heart Failure

“…This data supports the hypothesis of the 'lowest energy threshold' for terminal failure (Ingwall, 2009) and is consistent with the general concept of terminal heart failure pathogenesis. Also, we should admit, that ATP concentration in HCM cats was similar to the data obtained in dogs terminal HF from our previous research (Arkadievich, 2017), despite its very high concentration in the healthy myocardium. During cardiomyopathy progression and insufficiency of available sources of energy, the expression of the adaptive gene is developed, associated with CMC metabolism changes and switching to fetal genotype expression.…”

“…Then, we discovered high proteins concentration of GLUT1 than GLUT4 (Table 2), which may be explained by the prevalence of insulin-independent glucose transport in cat's heart. Additionally, we found a great difference between these proteins in comparison with the dogs studied earlier (Arkadievich, 2017). These features may also be explained by anaerobic predomination in the feline myocardium, due to different evolutionary lifestyles.…”

“…In HC group we found relatively high concentration of ATP in tissue samples, moreover it was higher in comparison to the dog's myocardium (Arkadievich, 2017). Then, we discovered high proteins concentration of GLUT1 than GLUT4 (Table 2), which may be explained by the prevalence of insulin-independent glucose transport in cat's heart.…”