Skip to main content
PMC home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2004 Dec;63(12):1627–1631. doi: 10.1136/ard.2003.015289

The myth of pulmonary Raynaud's phenomenon: the contribution of pulmonary arterial vasospasm in patients with systemic sclerosis related pulmonary arterial hypertension

D Mukerjee 1, L Yap 1, V Ong 1, C Denton 1, K Howells 1, C Black 1, J Coghlan 1
PMCID: PMC1754861  PMID: 15547087

Abstract

Objective: To investigate the contribution of cold induced pulmonary vasospasm by peripheral and central cold stimulus in exacerbating pulmonary arterial hypertension (PAH) in patients with systemic sclerosis undergoing cardiac catheterisation.

Methods: In a prospective pilot study, 21 patients with systemic sclerosis and catheter proven PAH had mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO) measured before and after peripheral (hand immersion into cold water at 10–15°C for two minutes if tolerated) and central (direct cold water at 4°C injected into the right atrium) cold pressor challenge. Markers of endothelial activation, platelet function, and nitric oxide degradation were measured in blood sampled from the pulmonary artery.

Results: 19 of the patients (mean (SD) age, 56 (4) years; baseline mPAP, 34 (8) mm Hg; PVR, 420 (87) dyne.s.cm–5; CO, 6.4 (1.8) l/min) tolerated cold hand immersion for the maximum two minute duration. All 21 tolerated central cold pressor challenge (three to five injections of 10 ml saline boluses at 4°C). There was no significant change in haemodynamics after cold challenge by either route of provocation. Levels of endothelin-1, von Willebrand factor, fibrinogen, and 3-nitrotyrosine were raised compared with control values in patients with systemic sclerosis but without PAH, but did not change significantly after peripheral cold challenge.

Conclusions: Pulmonary vasospasm in response to peripheral and centrally administered cold pressor challenge is unlikely to contribute to persistence of pulmonary arterial hypertension in patients with systemic sclerosis.

Full Text

The Full Text of this article is available as a PDF (77.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aalbers R., Groen H., Postma D. S., Van der Mark T. W., Wouda A. A., Reig R. P., Kallenberg C. G. Pulmonary function in patients presenting with Raynaud's phenomenon without an underlying connective tissue disease. A prospective, longitudinal study. J Rheumatol. 1989 Jan;16(1):36–41. [PubMed] [Google Scholar]
  2. Barr W. G., Fahey P. J. Reduction of pulmonary capillary blood volume following cold exposure in patients with Raynaud's phenomenon. Chest. 1988 Dec;94(6):1195–1199. doi: 10.1378/chest.94.6.1195. [DOI] [PubMed] [Google Scholar]
  3. Cannon P. J., Hassar M., Case D. B., Casarella W. J., Sommers S. C., LeRoy E. C. The relationship of hypertension and renal failure in scleroderma (progressive systemic sclerosis) to structural and functional abnormalities of the renal cortical circulation. Medicine (Baltimore) 1974 Jan;53(1):1–46. doi: 10.1097/00005792-197401000-00001. [DOI] [PubMed] [Google Scholar]
  4. Dziadzio M., Denton C. P., Smith R., Howell K., Blann A., Bowers E., Black C. M. Losartan therapy for Raynaud's phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis Rheum. 1999 Dec;42(12):2646–2655. doi: 10.1002/1529-0131(199912)42:12<2646::AID-ANR21>3.0.CO;2-T. [DOI] [PubMed] [Google Scholar]
  5. Ellis W. W., Baer A. N., Robertson R. M., Pincus T., Kronenberg M. W. Left ventricular dysfunction induced by cold exposure in patients with systemic sclerosis. Am J Med. 1986 Mar;80(3):385–392. doi: 10.1016/0002-9343(86)90711-4. [DOI] [PubMed] [Google Scholar]
  6. Fraenkel L., Tofler G. H., Zhang Y., Silbershatz H., D'Agostino R. B., Wilson P. W., Felson D. T. The associations between plasma levels of von Willebrand factor and fibrinogen with Raynaud's phenomenon in men and women. Am J Med. 2000 May;108(7):583–586. doi: 10.1016/s0002-9343(00)00350-8. [DOI] [PubMed] [Google Scholar]
  7. Furst D. E., Davis J. A., Clements P. J., Chopra S. K., Theofilopoulos A. N., Chia D. Abnormalities of pulmonary vascular dynamics and inflammation in early progressive systemic sclerosis. Arthritis Rheum. 1981 Nov;24(11):1403–1408. doi: 10.1002/art.1780241111. [DOI] [PubMed] [Google Scholar]
  8. Giesbrecht G. G. The respiratory system in a cold environment. Aviat Space Environ Med. 1995 Sep;66(9):890–902. [PubMed] [Google Scholar]
  9. Hall R. Self portrait of patient with severe cardiac pain awaiting surgery. Heart. 2001 Jul;86(1):11–11. doi: 10.1136/heart.86.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Herrick A. L., Illingworth K., Blann A., Hay C. R., Hollis S., Jayson M. I. Von Willebrand factor, thrombomodulin, thromboxane, beta-thromboglobulin and markers of fibrinolysis in primary Raynaud's phenomenon and systemic sclerosis. Ann Rheum Dis. 1996 Feb;55(2):122–127. doi: 10.1136/ard.55.2.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Herrick Ariane L. Treatment of Raynaud's phenomenon: new insights and developments. Curr Rheumatol Rep. 2003 Apr;5(2):168–174. doi: 10.1007/s11926-003-0046-0. [DOI] [PubMed] [Google Scholar]
  12. Kashimura O. [Mechanisms of cold-induced pulmonary hypertension in rats]. Nihon Eiseigaku Zasshi. 1995 Jun;50(2):616–621. doi: 10.1265/jjh.50.616. [DOI] [PubMed] [Google Scholar]
  13. Kozielski J., Ziora D., Dobosz J., Oklek K. Zachowanie sie parametrów badań czynnościowych układu oddechowego w chorobie Raynauda. Pol Arch Med Wewn. 1992 Jun;87(6):341–344. [PubMed] [Google Scholar]
  14. LeRoy E. C., Black C., Fleischmajer R., Jablonska S., Krieg T., Medsger T. A., Jr, Rowell N., Wollheim F. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988 Feb;15(2):202–205. [PubMed] [Google Scholar]
  15. MacDonald S. L., Rubens M. B., Hansell D. M., Copley S. J., Desai S. R., du Bois R. M., Nicholson A. G., Colby T. V., Wells A. U. Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparative appearances at and diagnostic accuracy of thin-section CT. Radiology. 2001 Dec;221(3):600–605. doi: 10.1148/radiol.2213010158. [DOI] [PubMed] [Google Scholar]
  16. Mayes Maureen D. Endothelin and endothelin receptor antagonists in systemic rheumatic disease. Arthritis Rheum. 2003 May;48(5):1190–1199. doi: 10.1002/art.10895. [DOI] [PubMed] [Google Scholar]
  17. Ploysongsang Y., Foad B. S. Lung function tests in connective tissue diseases associated with Raynaud's phenomenon. Respiration. 1984;46(2):222–230. doi: 10.1159/000194693. [DOI] [PubMed] [Google Scholar]
  18. Rajagopalan Sanjay, Pfenninger Dana, Kehrer Christine, Chakrabarti Anjan, Somers Emily, Pavlic Robert, Mukherjee Debabrata, Brook Robert, D'Alecy Louis G., Kaplan Mariana J. Increased asymmetric dimethylarginine and endothelin 1 levels in secondary Raynaud's phenomenon: implications for vascular dysfunction and progression of disease. Arthritis Rheum. 2003 Jul;48(7):1992–2000. doi: 10.1002/art.11060. [DOI] [PubMed] [Google Scholar]
  19. Regnard J. Cold and the airways. Int J Sports Med. 1992 Oct;13 (Suppl 1):S182–S184. doi: 10.1055/s-2007-1024633. [DOI] [PubMed] [Google Scholar]
  20. Rich S., Dantzker D. R., Ayres S. M., Bergofsky E. H., Brundage B. H., Detre K. M., Fishman A. P., Goldring R. M., Groves B. M., Koerner S. K. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. 1987 Aug;107(2):216–223. doi: 10.7326/0003-4819-107-2-216. [DOI] [PubMed] [Google Scholar]
  21. Sakamoto K., Houya I., Inoue K., Tanaka M., Suzuki T., Sakamoto Y., Matsuo H. An imbalance in plasma prostanoids in patients with Raynaud's phenomenon and pulmonary vasospasm. Eur Respir J. 1999 Jan;13(1):137–144. doi: 10.1183/09031936.99.13113799. [DOI] [PubMed] [Google Scholar]
  22. Shuck J. W., Oetgen W. J., Tesar J. T. Pulmonary vascular response during Raynaud's phenomenon in progressive systemic sclerosis. Am J Med. 1985 Feb;78(2):221–227. doi: 10.1016/0002-9343(85)90430-9. [DOI] [PubMed] [Google Scholar]
  23. Vancheeswaran R., Magoulas T., Efrat G., Wheeler-Jones C., Olsen I., Penny R., Black C. M. Circulating endothelin-1 levels in systemic sclerosis subsets--a marker of fibrosis or vascular dysfunction? J Rheumatol. 1994 Oct;21(10):1838–1844. [PubMed] [Google Scholar]
  24. Vergnon J. M., Barthélémy J. C., Riffat J., Boissier C., Claudy A., Emonot A. Raynaud's phenomenon of the lung. A reality both in primary and secondary Raynaud syndrome. Chest. 1992 May;101(5):1312–1317. doi: 10.1378/chest.101.5.1312. [DOI] [PubMed] [Google Scholar]
  25. Wise R. A., Wigley F., Newball H. H., Stevens M. B. The effect of cold exposure on diffusing capacity in patients with Raynaud's phenomenon. Chest. 1982 Jun;81(6):695–698. doi: 10.1378/chest.81.6.695. [DOI] [PubMed] [Google Scholar]
  26. Yamauchi K., Suzuki Y., Ichikawa Y., Takaya M., Arimori S. Abnormalities of pulmonary blood flow during cold exposure in systemic lupus erythematosus. Nucl Med Commun. 1988 Jun;9(6):423–430. doi: 10.1097/00006231-198806000-00006. [DOI] [PubMed] [Google Scholar]
  27. Zamora M. R., O'Brien R. F., Rutherford R. B., Weil J. V. Serum endothelin-1 concentrations and cold provocation in primary Raynaud's phenomenon. Lancet. 1990 Nov 10;336(8724):1144–1147. doi: 10.1016/0140-6736(90)92766-b. [DOI] [PubMed] [Google Scholar]
  28. ter Steege J. C., Koster-Kamphuis L., van Straaten E. A., Forget P. P., Buurman W. A. Nitrotyrosine in plasma of celiac disease patients as detected by a new sandwich ELISA. Free Radic Biol Med. 1998 Nov 15;25(8):953–963. doi: 10.1016/s0891-5849(98)00184-1. [DOI] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES