title: Chronic hypoxemia increases myocardial cytochrome oxidase.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pa, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Piel
authors.forename: Azeem R
authors.initials: AR
authors.lastname: Khan
authors.forename: Robert
authors.initials: R
authors.lastname: Waibel
authors.forename: Mariusz
authors.initials: M
authors.lastname: Birbach
authors.forename: Meryl S
authors.initials: MS
authors.lastname: Cohen
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Spray
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Deutschman
authors.forename: J William
authors.initials: JW
authors.lastname: Gaynor
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Levy
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D003576:Electron Transport Complex IV / Q000378:metabolism*; D000860:Hypoxia / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D013552:Swine
chemical_list: D003576:Electron Transport Complex IV