Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow

Sanjeev A. Datar, Eric G Johnson, Peter E. Oishi, Michael Johengen, Eric Tang, Angela Aramburo, Jubilee Barton, Hsuan Chang Kuo, Stephen Bennett, Konstantine Xoinis, Bhupinder Reel, Gokhan Kalkan, Eniko Sajti, Oscar Osorio, Gary W Raff, Michael A. Matthay, Jeffrey R. Fineman

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Abnormalities of the lymphatic circulation are well recognized in patients with congenital heart defects. However, it is not known how the associated abnormal blood flow patterns, such as increased pulmonary blood flow (PBF), might affect pulmonary lymphatic function and structure. Using well-established ovine models of acute and chronic increases in PBF, we cannulated the efferent lymphatic duct of the caudal mediastinal node and collected and analyzed lymph effluent from the lungs of lambs with acutely increased PBF (n = 6), chronically increased PBF (n = 6), and age-matched normal lambs (n = 8). When normalized to PBF, we found that lymph flow was unchanged following acute increases in PBF but decreased following chronic increases in PBF. The lymph: plasma protein ratio decreased with both acute and chronic increases in PBF. Lymph bioavailable nitric oxide increased following acute increases in PBF but decreased following chronic increases in PBF. In addition, we found perturbations in the transit kinetics of contrast material through the pleural lymphatics of lambs with chronic increases in PBF. Finally, there were structural changes in the pulmonary lymphatic system in lambs with chronic increases in PBF: lymphatics from these lambs were larger and more dilated, and there were alterations in the expression of vascular endothelial growth factor-C, lymphatic vessel endothelial hyaluronan receptor-1, and Angiopoietin-2, proteins known to be important for lymphatic growth, development, and remodeling. Taken together these data suggest that chronic increases in PBF lead to both functional and structural aberrations of lung lymphatics. These findings have important therapeutic implications that warrant further study.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume302
Issue number6
DOIs
StatePublished - Mar 2012

Keywords

  • Lymph flow
  • Lymphatic endothelial dysfunction
  • Lymphatic imaging

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

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    Datar, S. A., Johnson, E. G., Oishi, P. E., Johengen, M., Tang, E., Aramburo, A., Barton, J., Kuo, H. C., Bennett, S., Xoinis, K., Reel, B., Kalkan, G., Sajti, E., Osorio, O., Raff, G. W., Matthay, M. A., & Fineman, J. R. (2012). Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow. American Journal of Physiology - Lung Cellular and Molecular Physiology, 302(6). https://doi.org/10.1152/ajplung.00324.2011