Diverse forms of pulmonary hypertension remodel the arterial tree to a high shear phenotype

Roblee P Allen, Edward S Schelegle, Stephen H. Bennett

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Pulmonary hypertension (PH) is associated with progressive changes in arterial network complexity. An allometric model is derived that integrates diameter branching complexity between pulmonary arterioles of generation n and the main pulmonary artery (MPA) via a power-law exponent (X) in dn = dMPA2-n/X and the arterial area ratio β = 21-2/X. Our hypothesis is that diverse forms of PH demonstrate early decrements in X independent of etiology and pathogenesis, which alters the arteriolar shear stress load from a low-shear stress (X > 2, β > 1) to a high-shear stress phenotype (X < 2, β < 1). Model assessment was accomplished by comparing theoretical predictions to retrospective morphometric and hemodynamic measurements made available from a total of 221 PH-free and PH subjects diagnosed with diverse forms (World Health Organization; WHO groups I-IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial hypertension (IPAH), familial (FPAH), collagen vascular disease, and methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA), cardiac output (Q) and body weight (M), utilizing an allometric power-law prediction of X relative to a PH-free state. Comparisons of X between PAH-free and PAH subjects indicates a characteristic reduction in area that elevates arteriolar shear stress, which may contribute to mechanisms of endothelial dysfunction and injury before clinically defined thresholds of pulmonary vascular resistance and PH. We conclude that the evaluation of X may be of use in identifying reversible and irreversible phases of PH in the early course of the disease process.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume307
Issue number3
DOIs
StatePublished - 2014

Keywords

  • Allometry
  • Complexity
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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