Submitted on June 30, 2006
Accepted on August 14, 2006
Oxidative Stress Reversibly Inactivates Myocardial Enzymes during Cardiac Arrest
Arti Bashu Sharma1, Jie Sun2, Linda L. Howard3, Arthur G Williams, Jr.3, and Robert T Mallet2*
1 Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas, United States; United States
2 Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas, United States
3 Fort Worth, Texas, United States; Integrative Physiology, University of North Texas Health Science Center, Fort Worth, Texas, United States
* To whom correspondence should be addressed. E-mail: malletr{at}hsc.unt.edu.
Purpose: Oxidative stress during cardiac arrest may inactivate myocardial enzymes, and thereby exacerbate ischemic derangements of myocardial metabolism. This study examined the impact of cardiac arrest on left ventricular enzymes. Methods: Beagles were subjected to 5 min cardiac arrest and 5 min open chest cardiac compressions (OCCC) before epicardial DC countershocks were applied to restore sinus rhythm. Glutathione/glutathione disulfide redox state (GSH/GSSG) and a panel of enzyme activities were measured in snap-frozen left ventricle. To test whether oxidative stress during arrest inactivated the enzymes, metabolic (pyruvate) or pharmacological (N-acetylcysteine) antioxidants were infused iv for 30 min before arrest. Results: During cardiac arrest, activities of phosphofructokinase, citrate synthase, aconitase, malate dehydrogenase, creatine kinase, glucose 6-phosphate dehydrogenase and glutathione reductase fell by 56, 81, 55, 34, 42, 55 and 45%, respectively, coincident with 50% decline in GSH/GSSG. OCCC effected full recovery of glutathione reductase and partial recovery of citrate synthase and aconitase, in parallel with GSH/GSSG. Phosphofructokinase, malate dehydrogenase, creatine kinase and glucose 6-phosphate dehydrogenase recovered only after cardioversion. Antioxidant pretreatments augmented phosphofructokinase, aconitase and malate dehydrogenase activities before arrest, and enhanced these activities, as well as citrate synthase and glucose 6-phosphate dehydrogenase, during arrest. Conclusions: Cardiac arrest reversibly inactivates several important myocardial metabolic enzymes. Antioxidant protection of these enzymes implicates oxidative stress as a principal mechanism of enzyme inactivation during arrest.
