J Thorac Cardiovasc Surg 1997;114:1127-1128
© 1997 Mosby, Inc.
Effect of preoperative antioxidant supplements on perioperative myocardial injury
M. A. Wait , MD,
Paul A. Grayburn , MD
Division of Thoracic and Cardiovascular Surgery
Division of Cardiology
University of Texas Southwestern Medical Center
Dallas, TX 75235-8879
12/8/84945
To the Editor:
We read with great interest the article "Effect of Preoperative Supplementation With 
-Tocopherol and Ascorbic Acid on Myocardial Injury in Patients Undergoing Cardiac Operations," by Westhuyzen and associates.
1 We fully agree with the concept of ischemia-reperfusion injury to the myocardium and the mechanism most likely to be associated with that phenomenon (e.g., oxygen-derived free radical generation and subsequent cell membrane lipid peroxidation injury and microvascular injury). The supplementation of water-soluble and lipid-soluble antioxidant micronutrients in this study was found not to have had much differential effect (versus placebo) on the hard end points of irreversible injury in the subgroup of 36 patients; in a study of this size, one may not anticipate such a difference, if present, to be demonstrable. However, the methods of using hard end points of irreversible myocardial injury (creatine kinase MB isoenzyme levels, electrocardiographic QRS scores, and thallium single photon emission computed tomography defects) seem unsuited to detect more subtle, sublethal, functional end points of injury that are classically associated with myocardial stunning. Functional end points, such as requirement for inotropic agents, ejection-phase indices of myocardial performance, or hemodynamic outcome were not published. Lipid peroxidation products in coronary sinus effluent were not measured; this technique might have been a more sensitive instrument to measure clinically relevant differences in the antioxidant protective effect of -tocopherol and ascorbic acid.
Postischemic perioperative myocardial injury may take the form of myocardial infarction or necrosis with the typical enzyme leak and electrocardiographic changes, or it may be the result of sublethal injury as described in "myocardial stunning." 2 After an ischemic event and during reperfusion, superoxide anion, hydrogen peroxide, and the hydroxyl radical induce lipid peroxidation; these injuries cause either a transient calcium overload–induced proteolysis of myofilament contractile proteins or a direct peroxidation injury to myofilament protein (or both) during myocardial stunning. Cellular viability is maintained, and electrocardiographic changes and creatine kinase isoenzyme leak are typically absent, thus separating myocardial stunning from necrosis. The cellular extraction of thallium 201 is unaffected by hypoxia unless irreversible injury is present. 3 Also, pathophysiologic conditions of chronic hypoperfusion (hibernating myocardium) and postischemic dysfunction (stunned myocardium), in which regional contractile function is impaired in the presence of myocardial viability, do not adversely alter extraction of thallium 201. 3, 4 Therefore the absence of a demonstrable difference between antioxidant supplements and placebo in regard to the postoperative thallium 201 SPECT scan defects does not exclude a meaningful beneficial effect on myocardial stunning. Coronary sinus plasma levels of hydrogen peroxide, the nonspecific lipid peroxidation marker malondialdehyde, and hydroxy-conjugated diene fatty acids would provide a more sensitive tool to determine a protective effect of antioxidant supplemental therapy against stunning than would peripheral plasma creatine kinase MB isoenzyme levels. We are in agreement that the study design excluded a subpopulation of patients who may have demonstrated a more clinically relevant and statistically significant difference, that is, patients with depressed systolic function who require a more prolonged period of cardioplegic ischemic arrest. The findings of their study are without dispute; the population studied and the tools with which they were studied could have been chosen differently to determine the true effect of antioxidant supplementation on sublethal myocardial injury in patients undergoing cardioplegic ischemic arrest.
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