Khan Azeem R, Birbach Mariusz, Cohen Meryl S, Ittenbach Richard F, Spray Thomas L, Levy Richard J, Gaynor J William
Division of Cardiothoracic Surgery, Department of Surgery, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19106, USA.
Ann Thorac Surg. 2008 Feb;85(2):618-23. doi: 10.1016/j.athoracsur.2007.08.041.
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.
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.
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).
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.
紫绀型先天性心脏病患者循环中的心房利钠肽和脑利钠肽（BNP）水平升高，且与心室功能障碍的严重程度相关。我们评估了慢性低氧血症对左心室前心房利钠肽和前BNP（血浆激素的细胞质前体）的影响。
40只新生仔猪被随机分为肺动脉至左心房分流以造成低氧血症组或假开胸手术组。在手术后1周或2周对动物进行研究（四组，每组n = 10）。获取动脉血氧张力和血细胞比容。通过超声心动图测量左心室缩短分数。采集左心室组织并提取细胞质。通过蛋白质印迹分析测定前BNP水平。使用酶联免疫吸附测定法测定前心房利钠肽水平。
各治疗组之间在动脉血氧张力（p < 0.001）和血细胞比容（p < 0.001）方面观察到显著差异。两两比较表明，与对照仔猪相比，低氧血症仔猪在1周和2周时动脉血氧张力较低，血细胞比容较高。低氧血症动物在任何时候左心室缩短分数均未降低（p = 0.638）。低氧血症仔猪左心室前心房利钠肽降低（p = 0.029），而低氧血症仔猪在2周时左心室前BNP升高（p = 0.002）。
仅慢性低氧血症，即使在无心脏功能障碍的情况下，也足以增加心室前BNP水平。这一发现可能对紫绀型先天性心脏病患者临床管理中BNP水平的解读具有重要意义。
