Pulmonary vascular wall stiffness: An important contributor to the increased right ventricular afterload with pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is associated with structural and mechanical changes in the pulmonary vascular bed that increase right ventricular (RV) afterload. These changes, characterized by narrowing and stiffening, occur in both proximal and distal pulmonary arteries (PAs). An important consequence of arterial narrowing is increased pulmonary vascular resistance (PVR). Arterial stiffening, which can occur in both the proximal and distal pulmonary arteries, is an important index of disease progression and is a significant contributor to increased RV afterload in PH. In particular, arterial narrowing and stiffening increase the RV afterload by increasing steady and oscillatory RV work, respectively. Here we review the current state of knowledge of the causes and consequences of pulmonary arterial stiffening in PH and its impact on RV function. We review direct and indirect techniques for measuring proximal and distal pulmonary arterial stiffness, measures of arterial stiffness including elastic modulus, incremental elastic modulus, stiffness coefficient β and others, the changes in cellular function and the extracellular matrix proteins that contribute to pulmonary arterial stiffening, the consequences of PA stiffening for RV function and the clinical implications of pulmonary vascular stiffening for PH progression. Future investigation of the relationship between PA stiffening and RV dysfunction may facilitate new therapies aimed at improving RV function and thus ultimately reducing mortality in PH.

Keywords: biomechanics; hypertrophy; impedance; right ventricular dysfunction; vascular-ventricular coupling.

Figure 1

Representative pulmonary vascular impedance (magnitude Z and phase θ) spectra in a healthy mouse.

Figure 2

An illustrative example of pressure waveform and the derivation of pulse pressure (PP) and augmentation index (AI). Pi is the inflection point, which may present either in the systolic or diastolic phase.

Figure 3

Hemodynamic interactions between the right ventricle and proximal and distal pulmonary arteries. PA: pulmonary artery. VVC: ventricular-vascular coupling.

Figure 4

An illustrative example of vascular-ventricular coupling analysis from pressure-volume (PV) loops. Ventricular end-systolic elastance (Ees) and arterial effective elastance (E_a) are calculated from multiple loops by varying the preload.