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J Thorac Cardiovasc Surg 2005;130:1101-1106
© 2005 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

Chronic hypoxemia increases myocardial cytochrome oxidase

^a Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pa
^b Division of Cardiothoracic Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pa
^c Division of Cardiology, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pa
^d Children's Hospital of Philadelphia, University of Pennsylvania, and the Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia, Pa

Received for publication November 2, 2004; revisions received May 25, 2005; accepted for publication June 7, 2005.

^_* Address for reprints: Richard J. Levy, MD, Department of Anesthesiology and Critical Care Medicine, 9th Floor, Children's Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19106 (Email: levyri{at}email.chop.edu).

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.