Abstract:
Right‑ventricular (RV) failure is an event consequent to pathological RV hypertrophy commonly resulting from pulmonary arterial hypertension. This pathology is well characterised by RV diastolic dysfunction, impaired ejection, and reduced mechanical efficiency. However, whether the dynamic stiffness and crossbridge thermodynamics in the failing RV muscles are compromised remains uncertain. Pulmonary arterial hypertension was induced in the rat by an injection of monocrotaline, and RV trabeculae isolated from RV failing rats. Crossbridge mechano-energetics were characterised by subjecting the trabeculae to two interventions: (i) force‑length work‑loop contractions over a range of afterloads while measuring heat output, followed by careful partitioning of heat components into activation heat and crossbridge heat to separately assess mechanical efficiency and crossbridge efficiency, and (ii) sinusoidal‑perturbation of muscle length while trabeculae were actively contracting to interrogate crossbridge dynamic stiffness. We found that reduced mechanical efficiency is correlated with increased passive stress, reduced shortening and elevated activation heat. In contrast, the thermodynamics, specifically the efficiency of, and the stiffness characteristics of, crossbridges did not differ between the control and failing trabeculae and were not correlated with elevated passive stress or reduced shortening. We thus conclude that, despite diastolic dysfunction and mechanical inefficiency, crossbridge stiffness and thermodynamics are unaffected in RV failure following pulmonary arterial hypertension.