Compliance (C ) and resistance (R ) maintain a unique, inverse relationship in the pulmonary circulation, resulting in a constant characteristic time τ ¼ RC that has been observed in healthy subjects as well as patients with pulmonary arterial hypertension (PAH). However, little is known about the dependence of right ventricular (RV) function on the coupled changes in R and C in the context of this inverse relationship. We hypothesized three simple dependencies of RV ejection fraction (RVEF) on R and C. The first model (linear-R ) assumes a linear RVEF-R relation; the second (linear-C ) assumes a linear RVEF-C relation; and the third one combines the former two in a mixed linear model. We found that the linear-R model and the mixed linear model are in good agreement with clinical evidence. A conclusive validation of these models will require more clinical data. Longitudinal data in particular are needed to identify the time course of ventricular-vascular impairment in PAH. Simple models like the ones we present here, once validated, will advance our understanding of the mechanisms of RV failure, which could improve strategies to manage RV dysfunction in PAH. In understanding the progression of right ventricular (RV) failure in pulmonary arterial hypertension (PAH), a key knowledge gap is the mechanisms that underlie the transition from normal RV function to RV dysfunction and failure and how these transitions are dependent on changes in pulmonary vascular function as the disease progresses. Clinical studies have shown that the mechanical properties of the pulmonary vasculature (i.e., resistance [R] and compliance [C ]) correlate with mortality in PAH. [1][2][3] In addition, an inverse relationship exists between C and R in the pulmonary circulation. 4 The time constant τ ¼ RC has been found to be equal to ∼0.5 s in a large clinical population, including patients with and without PAH, patients with different types of PAH, and patients before and after treatment. 4-7 However, it is unclear how pathological changes in vascular R and C mediate RV dysfunction.Here we formulate three hypothetical models to describe the dependence of RV function on the metrics of pulmonary vascular function R and C. We hypothesize that RV function, expressed as RV ejection fraction (RVEF), depends linearly on R or C or on a combination of both. The results from the three models are evaluated on the basis of relevant clinical evidence.
METHODSTo describe the dependence of RV function on R and C, we chose a single metric of RV function. Under normal physiological conditions, known mechanisms of RV autoregulation preserve stroke volume (SV ) and cardiac output (CO) in the face of increased afterload. 8 The maintenance of SV or CO may persist in the adaptively functioning RV in mild or moderate PAH; thus, it would be difficult to correlate these parameters with the early phase of disease. RVEF may be a more sensitive metric of PAH progression than SV and CO. 9 RVEF correlates with mean pulmonary artery pressure 10 and pulmonary...