Published online before print June 1, 2004, doi: 10.1161/01.CIR.0000129305.25115.80
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;109:2872-2877.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Increased Atrial and Brain Natriuretic Peptides in Adults With Cyanotic Congenital Heart Disease
Enhanced Understanding of the Relationship Between Hypoxia and Natriuretic Peptide Secretion
From the Departments of Medicine (W.E.H., N.K.F., M.M.L.) and Physiology (Z.C., M.M.L.), University of Vermont College of Medicine, Burlington; Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Fla (H.J.K.); and Research Institute for Internal Medicine, University of Oslo, Oslo, Norway (C.H.).
Correspondence to William E. Hopkins, MD, University of Vermont College of Medicine, Cardiology Unit, McClure 1, 111 Colchester Ave, Burlington, VT 05401. E-mail william.hopkins{at}vtmednet.org
Received March 7, 2003; de novo received November 17, 2003; revision received February 26, 2004; accepted March 4, 2004.
Background— Brain natriuretic peptide (BNP) levels are used in the evaluation of patients with heart disease, yet there is little understanding of the effect of hypoxia on natriuretic peptide secretion. Furthermore, recent data suggest that oxytocin may mediate stretch-induced atrial natriuretic peptide (ANP) secretion.
Methods and Results— Ten patients with cyanotic congenital heart defects and 10 control subjects were studied. N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide levels were 4-fold (P=0.02) and 12-fold (P=0.03) greater in cyanotic patients than in control subjects. Cyanotic patients had reduced body water compared with control subjects, although the difference did not reach statistical significance (P=0.22). In a separate group of patients, cardiac myocytes were isolated from the right atrial appendage during CABG. The amount of oxygen in the buffered saline was varied to simulate hypoxia. Isolated hypoxic atrial myocytes had 43% fewer dense surface secretory granules compared with normoxic myocytes (P<0.0001). Immunohistochemical staining demonstrated decreased ANP and BNP in hypoxic compared with normoxic right atrial tissue. Isolated myocytes also degranulated when incubated with oxytocin (P<0.0001), but there was no difference in oxytocin levels in cyanotic patients compared with control subjects (P=0.49).
Conclusions— ANP and BNP are markedly elevated in adults with cyanotic congenital heart disease despite reduced body water. Our results show that hypoxia is a direct stimulus for ANP and BNP secretion in human cardiac myocytes. These findings may have implications for the interpretation of BNP levels in the assessment of patients with heart and lung disease.
Key Words: atrial natriuretic peptide • heart defects, congenital • hypoxia • natriuretic peptides, brain • oxytocin
This article has been cited by other articles:
 |
|
 |
|
  J.-H. Hsu, P. E. Oishi, R. L. Keller, O. Chikovani, T. R. Karl, A. Azakie, I. Adatia, and J. R. Fineman Perioperative B-type natriuretic peptide levels predict outcome after bidirectional cavopulmonary anastomosis and total cavopulmonary connection. J. Thorac. Cardiovasc. Surg., April 1, 2008; 135(4): 746 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Khan, M. Birbach, M. S. Cohen, R. F. Ittenbach, T. L. Spray, R. J. Levy, and J. W. Gaynor Chronic Hypoxemia Increases Ventricular Brain Natriuretic Peptide Precursors in Neonatal Swine Ann. Thorac. Surg., February 1, 2008; 85(2): 618 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. P. Rivers, J. McCord, R. Otero, G. Jacobsen, and M. Loomba Clinical utility of B-type natriuretic peptide in early severe sepsis and septic shock. J Intensive Care Med, November 1, 2007; 22(6): 363 - 373. [Abstract] [PDF]
|
|
|
|
 |
|
 C. S. Broberg, M. Ujita, S. Prasad, W. Li, M. Rubens, B. E. Bax, S. J. Davidson, B. Bouzas, J. S. R. Gibbs, J. Burman, et al. Pulmonary Arterial Thrombosis in Eisenmenger Syndrome Is Associated With Biventricular Dysfunction and Decreased Pulmonary Flow Velocity J. Am. Coll. Cardiol., August 14, 2007; 50(7): 634 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Struthers and C. Lang The potential to improve primary prevention in the future by using BNP/N-BNP as an indicator of silent 'pancardiac' target organ damage: BNP/N-BNP could become for the heart what microalbuminuria is for the kidney Eur. Heart J., July 2, 2007; 28(14): 1678 - 1682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Konstam Natriuretic Peptides and Cardiovascular Events: More Than a Stretch JAMA, January 10, 2007; 297(2): 212 - 214. [Full Text] [PDF]
|
|
|
|
 |
|
 B S Rana, J I Davies, M M Band, S D Pringle, A Morris, and A D Struthers B-type natriuretic peptide can detect silent myocardial ischaemia in asymptomatic type 2 diabetes Heart, July 1, 2006; 92(7): 916 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Y K Wong, S McSwiggan, N S J Kennedy, R S MacWalter, and A D Struthers B-type natriuretic peptide identifies silent myocardial ischaemia in stroke survivors Heart, April 1, 2006; 92(4): 487 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.D. Struthers and J. Davies B-type natriuretic peptide: a simple new test to identify coronary artery disease? QJM, October 1, 2005; 98(10): 765 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Jefic, J. W. Lee, D. Jefic, R. T. Savoy-Moore, and H. S. Rosman Utility of B-Type Natriuretic Peptide and N-terminal Pro B-Type Natriuretic Peptide in Evaluation of Respiratory Failure in Critically Ill Patients Chest, July 1, 2005; 128(1): 288 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Heeschen, C. W. Hamm, V. Mitrovic, N.-H. Lantelme, H. D. White, and for the Platelet Receptor Inhibition in Ischemic S N-Terminal Pro-B-Type Natriuretic Peptide Levels for Dynamic Risk Stratification of Patients With Acute Coronary Syndromes Circulation, November 16, 2004; 110(20): 3206 - 3212. [Abstract] [Full Text] [PDF]
|
|