Biochemical, mechanical and energetic characterization of right ventricular hypertrophy in the ferret heart.
Ferret right ventricular hypertrophy is characterized by a decreased and prolonged isometric contraction, associated with altered intracellular calcium (Ca2+) regulation. However myofibrillar composition, cross-bridge function and/or energy transfer may also be involved in these contractile disturbances. Therefore, mechanical properties of myofibrils have been studied with Triton X-100-skinned fibres and troponin (Tn) T and I composition has been examined. Mitochondrial function and functional activity of creatine kinase (CK) isoforms have been studied in saponin-skinned fibres of control (C) and hypertrophied (H) ferret right ventricle, to check for a possible mismatch between energy production and utilization. Our results show that neither TnT nor TnI isoform expression, nor myofibrillar Ca2+ responsiveness (similar apparent Ca2+ sensitivity and Hill coefficient) were affected by pressure-overload. Similarly, maximal tension and stiffness, as well as cross-bridge cycling rate (v)--assessed by quick length changes--were not significantly altered. Importantly, passive stiffness was dramatically increased (163 +/- 30 mN/mm2/microns for C v 500 +/- 121 mN/mm2/microns for H; P < 0.02). Moreover, there was a significant correlation between passive stiffness and cross-bridge cycling rate, indicating that a factor involved in the passive stiffness may affect cross-bridge kinetics. Oxidative capacity (normalized to ventricular dry weight), reflecting mitochondrial ATP production and mitochondrial CK efficacy, as well as myofibrillar CK efficacy (assessed by the shift of MgATP-rigor tension curves before and after phosphocreatine addition), were similar in both groups. These results demonstrate that ferret right ventricular pressure-overload was accompanied by a development of myofibrils and a parallel increase of energy production capacity, transfer and utilization. Decreased compliance, probably linked to an increase in the collagen fraction and/or alterations of the cytoskeletal architecture of the overloaded ventricle, could contribute to the slower time course and decreased amplitude of the isometric twitch.
Baudet
S
S
URA CNRS 1340, Laboratoire de Cardiologie Expérimentale, Hôpital Laënnec, Nantes, France.
Kuznetsov
A
A
Merciai
N
N
Gorza
L
L
Ventura-Clapier
R
R
D000818:Animals; D001696:Biomechanical Phenomena; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005289:Ferrets; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology*; D009210:Myofibrils / Q000201:enzymology; D011651:Pulmonary Artery / Q000502:physiology
D003402:Creatine Kinase