The pathophysiology of pulmonary hypertension in congenital heart disease

Robin H Steinhorn, Jeffrey R. Fineman

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Congenital heart disease with increased pulmonary blood flow commonly leads to the development of pulmonary hypertension and increased vascular reactivity. These serious sequelae are associated with the following two major categories of congenital heart defects: those resulting in increased pulmonary blood flow and increased pulmonary arterial pressure and those resulting in increased pulmonary venous pressure. Recent evidence that the pulmonary vascular endothelium is an important determinant of vascular tone has led to the hypothesis that endothelial injury, secondary to congenital heart disease with increased pulmonary blood flow, disrupts these regulatory mechanisms and thereby plays a role in the development of pulmonary hypertension and its associated increased vascular reactivity. In many animal models, endothelial dysfunction is a precursor for smooth muscle dysfunction, and there is an apparent progression from endothelial dysfunction to smooth muscle dysfunction as vascular changes progress. We established a chronic model of pulmonary hypertension with increased pulmonary blood flow in young lambs by placing a systemic-to-pulmonary shunt in utero. In this model, we found significant physiologic and molecular alternations of both the nitric oxide (NO) and endothelin signaling pathways, two important mechanisms by which the endothelium regulates pulmonary vascular tone. These alterations occur extremely early and precede severe anatomic changes. Early endothelial damage may contribute to the development of pulmonary hypertension and its associated enhanced pulmonary vascular reactivity.

Original languageEnglish (US)
Pages (from-to)970-974
Number of pages5
JournalArtificial Organs
Volume23
Issue number11
DOIs
StatePublished - Nov 1999
Externally publishedYes

Keywords

  • Congenital cardiac defects
  • Nitric oxide
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Biophysics

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