Wave reflection correlates with pulmonary vascular wall thickening in rats with pulmonary arterial hypertension

Wave reflection is enhanced in patients with pulmonary arterial hypertension (PAH), which may be derived from a mismatch of pulmonary artery (PA) impedance between proximal and distal sites of arteries. Whether enhanced wave reflection correlates with histological remodeling remains unknown, partly because lung biopsy is not clinically recommended for PAH patients due to substantial risks of mortality and morbidity.

Pulmonary hypertension was induced by SU5416 injection and 3-week hypoxic exposure (SuHx-PH) in rats, and hemodynamic and histological examinations were performed at 4weeks (SuHx-PH_4W) and 8weeks (SuHx-PH_8W) after SU5416 injection (n=7 each). Two groups of age-matched normal rats were also analyzed (n=7 each). Using an elastic tube with a 3-element Windkessel model, PA impedance was parameterized as pulmonary artery compliance (C_P), peripheral resistance (R_P), characteristic impedance (Z_C), and transmission time (T_D) in conducting arteries. Wave reflection was quantified as reflection gain at 0 Hz (Γ_gain) in the frequency domain, and as the ratio of peak backward pressure to peak forward pressure (K_B/F) in the time domain.

The SuHx-PH groups demonstrated increased R_P and Z_C, and decreased C_P and T_D compared with normal groups. Γ_gain and K_B/F were significantly higher in the SuHx-PH_8W group than in the SuHx-PH_4W group, and correlated strongly with a histological index of vascular wall thickening (R²=0.839, P<0.001 for Γ_gain and R²=0.775, P<0.001 for K_B/F).

Enhanced wave reflection caused by abnormal PA impedance correlates with histological remodeling, and may have a diagnostic value in clinical staging of PAH.