Background: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease, characterized by unexplained hypertrophy of the left ventricle. HCM features similar clinical and pathological characteristics in human beings and cats and is a common cause of sudden death and heart failure. Mitochondrial dysfunction and oxidative stress are well known to play a role in the development of various cardiovascular diseases. However, their roles in HCM remain unexplored.
Objectives
Methods: Cardiac muscle was obtained from eight cats diagnosed with naturally-occuring HCM (5 males; 2-10 years old, 6.3 ± 2.4 (mean ± SD)) and from nine age-matched control cats (CON) (3 males; 2-11 years, 4.9 ± 3.1). High-resolution respirometry was used to measure mitochondrial function in permeabilized, cardiac muscle fibres. Oxidative stress was assessed by measurements of mitochondrial H2O2 generation and thiobarbituric acid reactive substances (TBARS).
Results: In heart muscle of HCM cats, complex-I-linked state 3-respiration was significantly decreased (30 ± 16 pmol s -1 mg-1) compared to CON (64 ± 26 pmol s -1 mg-1) (P=0.006). Fatty acid oxidation with palmitoyl-carnitine and octanoyl-carnitine was significantly decreased in HCM hearts (12 ± 5 pmol s -1 mg-1) and (15 ± 4 pmol s -1 mg-1) compared to CON (28 ± 8 pmol s -1 mg-1) and (42 ± 16 pmol s -1 mg-1), respectively (P=0.0004). Mitochondrial H2O2 generation during state 3, with complex I-linked substrates, was significantly higher in HCM hearts compared to CON (P<0.05). TBARS in heart tended to be increased in HCM cats compared to CON.
Conclusion: Findings of the study indicate that mitochondrial dysfunction and enhanced oxidative stress may play an important role in the pathogenesis of feline HCM in the occult stage of disease.