Pulmonary vascular mechanics: important contributors to the increased right ventricular afterload of pulmonary hypertension

New Findings•  What is the topic of this review? This article reviews pulmonary vascular and right ventricular (RV) changes due to hypoxic pulmonary hypertension (HPH), which is a type of pulmonary hypertension (PH) found clinically and has been widely used to induce PH in animal models. As research into clinical PH progression broadens to include RV as well as pulmonary vascular remodelling, an improved understanding of the effects of HPH on the RV is required. •  What advances does it highlight? This article highlights the moderate, adaptive and reversible nature of RV and pulmonary vascular remodelling in HPH. Moreover, we show that increased haematocrit in HPH contributes significantly to RV overload, which warrants additional attention.Chronic hypoxia causes pulmonary vasoconstriction and vascular remodelling, which lead to hypoxic pulmonary hypertension (HPH). Hypoxic pulmonary hypertension is associated with living at high altitudes and is a complication of many lung diseases, including chronic obstructive pulmonary disease, cystic fibrosis and obstructive sleep apnoea. Pulmonary vascular changes that occur with HPH include stiffening and narrowing of the pulmonary arteries that appear to involve all vascular cell types and sublayers of the arterial wall. Right ventricular (RV) changes that occur with HPH include RV hypertrophy and RV fibrosis, often with preserved systolic and diastolic function and ventricular–vascular coupling efficiency. Both vascular stiffening and vascular narrowing are important contributors to RV afterload via increases in oscillatory and steady ventricular work, respectively. The increased blood viscosity that occurs in HPH can be dramatic and is another important contributor to RV afterload. However, the viscosity, vascular mechanics and ventricular changes that occur with HPH are all reversible. Furthermore, even with continued hypoxia the vascular remodelling does not progress to the obliterative, plexiform lesions that are seen clinically in severe pulmonary hypertension. In animal models, the RV changes appear adaptive, not maladaptive. In summary, HPH‐induced vascular mechanical changes affect ventricular function, but both are adaptive and reversible, which differentiates HPH from severe pulmonary hypertension. The mechanisms of adaptation and reversibility may provide useful insight into therapeutic targets for the clinical disease state.