Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae

Abstract

Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their peak external work output was lower due to reduced extent and velocity of shortening. Despite lower peak work output, suprabasal enthalpy was unaffected, thereby rendering suprabasal efficiency lower. Crossbridge efficiency, however, was unaffected. In contrast, LV trabeculae from PAH rats maintained normal mechano-energetic performance. Pulmonary arterial hypertension reduces the suprabasal energy efficiency of hypertrophied right ventricular tissues as a consequence of the increased energy cost of Ca cycling.

Myocardial proteomic profile in pulmonary arterial hypertension

“…Increased levels of these proteins may suggest that a failing LV with apoptosis-induced reduction in the number of functional cardiomyocytes (and therefore reduced force production) and reduced myosin content (also causing reduction in force production by a reduction in the number of available cross bridges per sarcomere) tries to maintain its function by increasing Ca 2+ currents. This hypothesis may be confirmed by findings of Pham et al study which have proved that LV trabeculae from PAH rats maintained normal mechano-energetic performance despite its atrophy 38 .…”

An Equivocal Final Link – Quantitative Determination of the Thermodynamic Efficiency of ATP Hydrolysis – Sullies the Chain of Electric, Ionic, Mechanical and Metabolic Steps Underlying Cardiac Contraction

“…Nor were differences revealed among trabecula from Dahl salt-sensitive rats and their congenic controls, whether fed low-or high-salt diets (Tran et al, 2016). Similar results obtained in trabecula from both ventricles of hearts in which pulmonary arterial hypertension had been induced by injection of monocrotaline and untreated control trabecula (Pham et al, 2018). Hence, in each of these models overall cardiac function was compromised but the energetics of cycling cross-bridges and the associated mitochondrial energy supply were unaffected.…”

The protective of baicalin on pulmonary hypertension vascular remodeling through regulation of TNF-α signaling pathway

“…Pulmonary hypertension (PH) is a kind of refractory rare lung diseases, distal pulmonary arterial remodeling is the characteristic of it [16][17][18]. The pathogenesis of PH is not clear yet, and no effective therapy is available for it.…”