Pulmonary vein banding-induced pulmonary venous congestion causes pulmonary hypertension in rats

Abstract

<b>Introduction:</b> Heart failure with preserved ejection fraction (HFpEF) is frequently complicated by the development of pulmonary hypertension (PH) with combined pre- and post-capillary changes in the vascular wall, assumed to be mainly caused by left ventricular (LV) diastolic dysfunction with hindrance of pulmonary venous outflow (pulmonary venous congestion). <b>Aims and objectives:</b> We aimed to establish a novel PH model that purely mimics this venous congestion. <b>Methods:</b> Wistar-Kyoto rats underwent partial occlusion of the left pulmonary veins to induce pulmonary venous congestion (n=9 rats) or Sham surgery (n=10 rats). Cardio-pulmonary phenotyping was performed via non-invasive echocardiographic imaging before and 12-weeks after disease induction, along with terminal intra-cardiac bi-ventricular catheterization. Arterial and venous remodeling was quantified in paraffin-embedded lung sections (wall thickness, degree of muscularization) and in thick vibratome sections (&gt;300um) using 3D imaging approaches. <b>Results:</b> 12-weeks of pulmonary vein banding increased right ventricular systolic pressure (23.6±2.2 vs. 18.8±2.3 mmHG, p&lt;0.05) and caused right ventricular hypertrophy (RV/BW, 0.50±0.05 vs. 0.46±0.06, p&lt;0.05) when compared with Sham operated controls; while LV systolic pressure (89.7±13.25 vs. 100.9±21.7 mmHG, p&lt;0.05) and LV mass (LV/BW, 2.40±0.10 vs. 2.49±0.09, p&lt;0.05) decreased. These changes were accompanied by increases in arterial and venous muscularization of small pulmonary vessels. <b>Conclusions:</b> These data demonstrate that PVB-induced pulmonary venous congestion causes PH and suggest a pre- and post-capillary remodeling component.