V L Lakomkin1, A A Abramov1, I M Studneva1, A D Ulanova2, I M Vikhlyantsev3, A V Prosvirnin1, E V Lukoshkova1, V I Kapelko1. 1. National Cardiology Research Center, Moscow. 2. Institute for Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Moscow Region. 3. Institute for Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Moscow Region Pushchino State Institute for Natural Science, Pushchino, Moscow Region.
Abstract
RELEVANCE: Diastolic dysfunction occurring at hypertension, obesity, diabetes, or treatment with doxorubicin tends to prevail in all patterns of chronic heart failure. Lack of effective therapy forces to look more into the metabolic processes in cardiomyocytes. OBJECTIVE: Assess energy metabolism in cardiomyocytes and changes in titin, a giant myofibril protein that responsible for their elasticity. MATERIAL AND METHODS: The study model was cardiomyopathy occurring after the 4-week administration of doxorubicin (2 mg/kg weekly). Diastolic dysfunction was identified by echocardiography and catheterization with the simultaneous measurement of pressure and volume of the left ventricle (LV). RESULTS: The levels of adenine nucleotides and phosphocreatine in the heart of animals treated with doxorubicin differed little from the normal values, but lactate levels were increased manifold. A 50% increase in the level of titin phosphorylation was detected, which correlated (r = 0,94) with a nearly twofold increase in the share of a more elastic N2BA-isoform of this protein. CONCLUSION: This form of diastolic dysfunction involves the activation of anaerobic metabolism and increased stretching of myofibrils facilitating LV filling.
RELEVANCE: Diastolic dysfunction occurring at hypertension, obesity, diabetes, or treatment with doxorubicin tends to prevail in all patterns of chronic heart failure. Lack of effective therapy forces to look more into the metabolic processes in cardiomyocytes. OBJECTIVE: Assess energy metabolism in cardiomyocytes and changes in titin, a giant myofibril protein that responsible for their elasticity. MATERIAL AND METHODS: The study model was cardiomyopathy occurring after the 4-week administration of doxorubicin (2 mg/kg weekly). Diastolic dysfunction was identified by echocardiography and catheterization with the simultaneous measurement of pressure and volume of the left ventricle (LV). RESULTS: The levels of adenine nucleotides and phosphocreatine in the heart of animals treated with doxorubicin differed little from the normal values, but lactate levels were increased manifold. A 50% increase in the level of titin phosphorylation was detected, which correlated (r = 0,94) with a nearly twofold increase in the share of a more elastic N2BA-isoform of this protein. CONCLUSION: This form of diastolic dysfunction involves the activation of anaerobic metabolism and increased stretching of myofibrils facilitating LV filling.