Cross-bridge thermodynamics in pulmonary arterial hypertensive right-ventricular failure

Right-ventricular (RV) failure is an event consequent to pathological RV hypertrophy commonly resulting from pulmonary arterial hypertension. This pathology is well characterized by RV diastolic dysfunction, impaired ejection, and reduced mechanical efficiency. However, whether the dynamic stiffness and cross-bridge thermodynamics in the failing RV muscles are compromised remains uncertain. Pulmonary arterial hypertension was induced in the rat by injection of monocrotaline, and RV trabeculae were isolated from RV failing rats. Cross-bridge mechano-energetics were characterized by subjecting the trabeculae to two interventions: 1) 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 cross-bridge heat to separately assess mechanical efficiency and cross-bridge efficiency, and 2) sinusoidal-perturbation of muscle length while trabeculae were actively contracting to interrogate cross-bridge 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, cross bridges 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, cross-bridge stiffness and thermodynamics are unaffected in RV failure following pulmonary arterial hypertension.NEW & NOTEWORTHY This study characterizes cross-bridge mechano-energetics and dynamic stiffness of right-ventricular trabeculae isolated from a rat model of pulmonary hypertensive right-ventricular failure. Failing trabeculae showed increased passive force but normal active force. Their lower mechanical efficiency is found to be driven by an increase in the energy expenditure arising from contractile activation. This does not reflect a change in their cross-bridge stiffness and efficiency.