Chronic hypoxemia increases ventricular brain natriuretic peptide precursors in neonatal swine.
BACKGROUND
Circulating levels of atrial natriuretic peptide and brain natriuretic peptide (BNP) are elevated in patients with cyanotic congenital heart disease and associated with the severity of ventricular dysfunction. We evaluated the effect of chronic hypoxemia on left ventricle pro-atrial natriuretic peptide and pro-BNP, the cytoplasmic precursors of the plasma hormones.


METHODS
Forty newborn piglets were randomized to placement of a pulmonary artery to left atrium shunt to create hypoxemia or sham thoracotomy. Animals were studied at 1 or 2 weeks after the procedure (four groups, n = 10 per group). Arterial oxygen tension and hematocrit were obtained. Left ventricular shortening fraction was measured by echocardiography. Left ventricular tissue was harvested and cytoplasm was extracted. Pro-BNP levels were determined by Western blot analysis. Pro-atrial natriuretic peptide levels were determined using enzyme-linked immunosorbent assay.


RESULTS
Significant differences among treatment groups were observed for arterial oxygen tension (p < 0.001) and hematocrit (p < 0.001). Pairwise comparisons indicated lower arterial oxygen tension and higher hematocrit for hypoxemic piglets compared with control piglets at 1 and 2 weeks. Left ventricular shortening fraction was not decreased in the hypoxemic animals at any time (p = 0.638). Left ventricular pro-atrial natriuretic peptide decreased in hypoxemic piglets (p = 0.029), whereas left ventricular pro-BNP increased in hypoxemic piglets at 2 weeks (p = 0.002).


CONCLUSIONS
Chronic hypoxemia alone, even in the absence of cardiac dysfunction, is sufficient to increase ventricular levels of pro-BNP. This finding may have implications for the interpretation of BNP levels in the clinical management of patients with cyanotic congenital heart disease.
Khan
Azeem R
AR
Division of Cardiothoracic Surgery, Department of Surgery, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19106, USA.
Birbach
Mariusz
M
Cohen
Meryl S
MS
Ittenbach
Richard F
RF
Spray
Thomas L
TL
Levy
Richard J
RJ
Gaynor
J William
JW
D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000032:analysis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006330:Heart Defects, Congenital / Q000378:metabolism / Q000503:physiopathology*; D000860:Hypoxia / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000032:analysis / Q000378:metabolism*; D011336:Probability; D011379:Prognosis; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D013552:Swine
D015415:Biomarkers; C099254:N-terminal proatrial natriuretic peptide; D011498:Protein Precursors; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor