Skip to main content
SpringerLink
Log in

Systemic Arterial Endothelial Function in Children and Young Adults with Idiopathic Pulmonary Arterial Hypertension: Is there a Relation to Pulmonary Endothelium-Dependent Relaxation?

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

Pulmonary arterial endothelial function is known to be affected in patients with idiopathic pulmonary arterial hypertension (IPAH). Current reports also detected peripheral systemic arterial dysfunction in IPAH patients. The purpose of this study was to assess whether there is a relation between pulmonary arterial and systemic arterial endothelial function. Pulmonary arterial endothelium-dependent relaxation was assessed by changes in pulmonary blood flow in response to acetylcholine which were determined using intravascular Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to acetylcholine relative to baseline values. Systemic arterial endothelial function was assessed by the vascular response to reactive hyperemia, and was recorded non-invasively by peripheral arterial finger tonometry under standardized conditions. Thirteen children and young adults [mean age 16.7 (±5.6) years] with IPAH and 13 age-/gender-matched controls were included in the study. Digital reactive hyperemic index (RHI) of the IPAH patients was 1.54 (±0.69), and of the controls was 1.67 (±0.66) [p = 0.64]. The mean baseline flow velocity in the segmental pulmonary artery of all patients was 18.5 (±5.5) cm/s, increasing to 27.4 (±12.3) cm/s (p = 0.003) during acetylcholine infusion. The calculated mean PFR was 1.48 (±0.4). There was no significant correlation between the PFR and RHI (r = 0.19; p = 0.54). According to our results, systemic arterial endothelial function assessed by peripheral arterial finger tonometry was not significantly impaired in children and young adults with IPAH compared with age-/gender-matched controls. There was no correlation between systemic arterial and pulmonary arterial endothelial function, suggesting that different mechanisms may contribute to their pathogenesis and progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D et al (1995) Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 26(5):1235–1241

    Article  CAS  PubMed  Google Scholar 

  2. Apitz C, Zimmermann R, Kreuder J, Jux C, Latus H, Pons-Kuhnemann J et al (2012) Assessment of pulmonary endothelial function during invasive testing in children and adolescents with idiopathic pulmonary arterial hypertension. J Am Coll Cardiol 60(2):157–164

    Article  PubMed  Google Scholar 

  3. Berger RM, Beghetti M, Humpl T, Raskob GE, Ivy DD, Jing ZC et al (2012) Clinical features of paediatric pulmonary hypertension: a registry study. Lancet 379(9815):537–546

    Article  PubMed Central  PubMed  Google Scholar 

  4. Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman A (2004) Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol 44(11):2137–2141

    Article  PubMed  Google Scholar 

  5. Bull TM, Golpon H, Hebbel RP, Solovey A, Cool CD, Tuder RM et al (2003) Circulating endothelial cells in pulmonary hypertension. Thromb Haemost 90(4):698–703

    CAS  PubMed  Google Scholar 

  6. Celermajer DS, Cullen S, Deanfield JE (1993) Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics. Circulation 87(2):440–446

    Article  CAS  PubMed  Google Scholar 

  7. Dinh Xuan AT, Higenbottam TW, Clelland C, Pepke-Zaba J, Wells FC, Wallwork J (1990) Acetylcholine and adenosine diphosphate cause endothelium-dependent relaxation of isolated human pulmonary arteries. Eur Respir J 3(6):633–638

    CAS  PubMed  Google Scholar 

  8. Dinh-Xuan AT, Higenbottam TW, Clelland CA, Pepke-Zaba J, Cremona G, Butt AY et al (1991) Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease. N Engl J Med 324(22):1539–1547

    Article  CAS  PubMed  Google Scholar 

  9. Dorfmüller P, Perros F, Balabanian K, Humbert M (2003) Inflammation in pulmonary arterial hypertension. Eur Respir J 22(2):358–363

    Article  PubMed  Google Scholar 

  10. Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P et al (2012) The assessment of endothelial function: from research into clinical practice. Circulation 126(6):753–767

    Article  PubMed Central  PubMed  Google Scholar 

  11. Friedman D, Szmuszkovicz J, Rabai M, Detterich JA, Menteer J, Wood JC (2012) Systemic endothelial dysfunction in children with idiopathic pulmonary arterial hypertension correlates with disease severity. J Heart Lung Transplant 31(6):642–647

    Article  PubMed Central  PubMed  Google Scholar 

  12. Hughes R, Tong J, Oates C, Lordan J, Corris PA (2005) Evidence for systemic endothelial dysfunction in patients and first-order relatives with pulmonary arterial hypertension. Chest 128(6 Suppl):617S

    Article  CAS  PubMed  Google Scholar 

  13. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP et al (2003) Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J 146(1):168–174

    Article  PubMed  Google Scholar 

  14. Loscalzo J (1992) Endothelial dysfunction in pulmonary hypertension. N Engl J Med 327(2):117–119

    Article  CAS  PubMed  Google Scholar 

  15. Peled N, Bendayan D, Shitrit D, Fox B, Yehoshua L, Kramer MR (2008) Peripheral endothelial dysfunction in patients with pulmonary arterial hypertension. Respir Med 102(12):1791–1796

    Article  PubMed  Google Scholar 

  16. Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE et al (2010) Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J 31(9):1142–1148

    Article  PubMed  Google Scholar 

  17. Takase B, Hamabe A, Satomura K, Akima T, Uehata A, Matsui T et al (2006) Comparable prognostic value of vasodilator response to acetylcholine in brachial and coronary arteries for predicting long-term cardiovascular events in suspected coronary artery disease. Circ J 70(1):49–56

    Article  PubMed  Google Scholar 

  18. Velez-Roa S, Ciarka A, Najem B, Vachiery JL, Naeije R, van de Borne P (2004) Increased sympathetic nerve activity in pulmonary artery hypertension. Circulation 110(10):1308–1312

    Article  PubMed  Google Scholar 

  19. Vogel RA, Corretti MC, Plotnick GD (2000) A comparison of brachial artery flow-mediated vasodilation using upper and lower arm arterial occlusion in subjects with and without coronary risk factors. Clin Cardiol 23(8):571–575

    Article  CAS  PubMed  Google Scholar 

  20. Wolff B, Lodziewski S, Bollmann T, Opitz CF, Ewert R (2007) Impaired peripheral endothelial function in severe idiopathic pulmonary hypertension correlates with the pulmonary vascular response to inhaled iloprost. Am Heart J 153(6):1088.e1–1088.e7

    Article  Google Scholar 

  21. Xu W, Kaneko FT, Zheng S, Comhair SA, Janocha AJ, Goggans T et al (2004) Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension. FASEB J 18(14):1746–1748

    CAS  PubMed  Google Scholar 

  22. Zimmermann R, Kreuder J, Michel-Behnke I, Voelkel NF, Schranz D (2006) Pulmonary flow reserve in children with idiopathic pulmonary arterial hypertension: implications for diagnosis and therapy. Eur J Med Res 11(5):208–213

    CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Pediatric Heart Centre, Justus-Liebig-University, Giessen, Germany

    Heiner Latus, Anna Werz, Ines Kock, Stefan Rupp, Gunter Kerst, Joachim Kreuder, Dietmar Schranz & Christian Apitz

Authors
  1. Heiner Latus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Werz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ines Kock
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefan Rupp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gunter Kerst
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joachim Kreuder
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dietmar Schranz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christian Apitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christian Apitz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Latus, H., Werz, A., Kock, I. et al. Systemic Arterial Endothelial Function in Children and Young Adults with Idiopathic Pulmonary Arterial Hypertension: Is there a Relation to Pulmonary Endothelium-Dependent Relaxation?. Pediatr Cardiol 35, 844–850 (2014). https://doi.org/10.1007/s00246-014-0864-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-014-0864-z

Keywords

Search

Navigation