Piel David A, Khan Azeem R, Waibel Robert, Birbach Mariusz, Cohen Meryl S, Spray Thomas L, Deutschman Clifford S, Gaynor J William, Levy Richard J
Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pa, USA.
J Thorac Cardiovasc Surg. 2005 Oct;130(4):1101-6. doi: 10.1016/j.jtcvs.2005.06.030.
Cyanotic patients have potentially decreased tissue oxygen tension. Cytochrome oxidase catalyzes the reduction of oxygen and is integral to adenosine triphosphate production. Cytochrome oxidase subunit I, the active site, is encoded by mitochondrial DNA. Using a newborn swine model of chronic hypoxemia, we evaluated ventricular cytochrome oxidase subunit I mRNA and protein expression and assessed cytochrome oxidase activity.
Thirty-two newborn piglets underwent thoracotomy and placement of a pulmonary artery-to-left atrium shunt or sham operation. Two weeks later, partial pressure of arterial oxygen, hematocrit, and left ventricular shortening fraction values were compared with baseline values. Northern blot hybridization and protein immunoblotting for ventricular cytochrome oxidase subunit I were performed. Cytochrome oxidase kinetic activity was measured. Heme a,a3 content and turnover number were determined. Significance was assessed with a t test.
Baseline partial pressure of arterial oxygen and hematocrit values were similar. Hypoxemic piglets had a lower partial pressure of arterial oxygen of 38 +/- 10 mm Hg (P < .001) and higher hematocrit value of 31.4% +/- 2.9% (P < .001) compared with a partial pressure of arterial oxygen of 140 +/- 47 mm Hg and hematocrit value of 24.6% +/- 3.9% after the sham operation. Baseline and postprocedure left ventricular shortening fraction were similar within and between groups. Chronic hypoxemia increased right ventricular and left ventricular cytochrome oxidase I mRNA and protein by more than 1.4-fold. Cytochrome oxidase activity increased significantly in hypoxemia by 2.5-fold compared with that seen after the sham operation. Heme a,a3 content and turnover number increased by 1.5-fold during hypoxemia.
Chronic hypoxemia increases cytochrome oxidase I message, protein expression, and activity. The increase in kinetics was due to increased enzyme content and catalytic activity. This is a possible adaptive mechanism that might preserve organ function during chronic hypoxemia.
发绀患者的组织氧张力可能降低。细胞色素氧化酶催化氧的还原，是三磷酸腺苷生成所必需的。细胞色素氧化酶亚基I作为活性位点，由线粒体DNA编码。我们使用新生猪慢性低氧血症模型，评估心室细胞色素氧化酶亚基I的mRNA和蛋白表达，并测定细胞色素氧化酶活性。
32只新生仔猪接受开胸手术并进行肺动脉至左心房分流术或假手术。两周后，将动脉血氧分压、血细胞比容和左心室缩短分数值与基线值进行比较。对心室细胞色素氧化酶亚基I进行Northern印迹杂交和蛋白免疫印迹分析。测定细胞色素氧化酶动力学活性。测定血红素a,a3含量和周转数。采用t检验评估差异的显著性。
基线动脉血氧分压和血细胞比容值相似。与假手术后动脉血氧分压140±47 mmHg和血细胞比容值24.6%±3.9%相比，低氧血症仔猪的动脉血氧分压较低，为38±10 mmHg（P<.001），血细胞比容值较高，为31.4%±2.9%（P<.001）。组内和组间基线及术后左心室缩短分数相似。慢性低氧血症使右心室和左心室细胞色素氧化酶I的mRNA和蛋白增加超过1.4倍。与假手术后相比，低氧血症时细胞色素氧化酶活性显著增加2.5倍。低氧血症期间血红素a,a3含量和周转数增加1.5倍。
慢性低氧血症增加细胞色素氧化酶I的信使核糖核酸、蛋白表达和活性。动力学增加是由于酶含量和催化活性增加。这是一种可能的适应性机制，可能在慢性低氧血症期间维持器官功能。
