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

Exp Physiol. 2013 Aug;98(8):1267-73. doi: 10.1113/expphysiol.2012.069096. Epub 2013 May 10.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Heart Ventricles / physiopathology*
  • Humans
  • Hypertension, Pulmonary / physiopathology*
  • Hypoxia / physiopathology
  • Pulmonary Artery / physiopathology*
  • Ventricular Function, Right / physiology*