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Original Articles: Cardiovascular

Chronic Hypoxemia Increases Ventricular Brain Natriuretic Peptide Precursors in Neonatal Swine

^a Division of Cardiothoracic Surgery, Department of Surgery, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
^b Division of Cardiology, Department of Pediatrics, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
^c Biostatistics and Data Management Core, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
^d Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Accepted for publication August 21, 2007.

^_* Address correspondence to Dr Gaynor, Division of Cardiothoracic Surgery, Department of Surgery, The Children’s Hospital of Philadelphia, 34th St and Civic Center Blvd, Suite 8527, Philadelphia, PA 19106 (Email: gaynor{at}email.chop.edu).

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.

This article has been cited by other articles:

				O. Arjamaa and M. Nikinmaa Natriuretic peptides in hormonal regulation of hypoxia responses Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R257 - R264. [Abstract] [Full Text] [PDF]