N-acetylcysteine and Myocardial Infarct

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Reference: Sochman J, Vrbska J, Musilova B, Rocek M. Infarct size limitation: acute N-acetylcysteine defense (ISLAND Trial): preliminary analysis and report after the first 30 patients. Clin Cardiol 1996; 19:94-100.

Summary: Medical doctors working in the Coronary Care Unit (CCU) and Department of Radiology at the Institute for Clinical and Experimental Medicine in Prague, Czech Republic, reported on their initial clinical observations in an ongoing study of myocardial infarct (MI) and N-acetylcysteine (NAC). From an initial group of 44 patients admitted to the CCU with a first evolving anterior wall MI and ischemic time of less than six hours, 30 subjects were selected meeting electrocardiogram-based eligibility criteria. All subjects were treated with nitroglycerin and 200 mg of aspirin upon admission to the CCU, and subsequently with 2.5-5.0 mg of intravenous midazolam, as well as 1.5 mil.u of streptokinase in saline infusion. In addition to the streptokinase, 14 of the 30 subjects also received 100 mg/kg body weight of NAC. Half of the NAC was delivered as undiluted bolus within 2-3 minutes following initiation of the infusion. The other half was delivered over 30 minutes in a 200 ml saline solution. NAC-treated subjects showed significantly higher left ventricular ejection fraction (LVEF) than subjects receiving no NAC. In addition, morphology of the QRS complexes in electrocardiographic data was more favorable for NAC-treated subjects. In studies of creatine kinase release, the NAC-treated group also showed significantly reduced enzyme release activity, suggesting the smallest extent of structural damage to the myocardium.

Comments/Opinions: There is perhaps no more explosive area of research in nutritional biochemistry than the area of sulfur and thiol metabolism. A recent, outstanding review by Stamler and Slivka (Stamler JS, Slivka A. Biological chemistry of thiols in the vasculature and in vascular-related disease. Nutr Rev 1996; 54(1):1-30.) has covered this territory in detail. NAC-related support of cardiovascular function could include a wide variety of biochemical mechanisms, including cellular protection via direct scavenging of reactive oxygen species, provision of sulfhydryl groups required for relaxation of vascular smooth muscle, inhibition of platelet activity, or modulation of endothelium-derived releasing factor (EDRF) and its inhibitory effect on platelet activity. A combination of these mechanisms was no doubt at work in the current study, resulting in NAC-based limitation of infarct size. Stamler and Slivka also point out in their review, however, that cysteine, like homocysteine, may have potentially atherogenic effects as well, via inhibition of vitamin B6-dependent enzymes. In addition, cysteine may also have cytotoxic potential related to overstimulation of the n-methyl-d-aspartate (NMDA) subtype of the glutamate receptor system. For both reasons, it's important here to remember the difference between acute therapeutic use of a nutrient and chronic preventive use, and the known compromises in sulfur metabolism which have been determined to accompany myocardial infarct.

Equally important to remember here is the intrinsic danger of selecting a single, isolated nutrient for candidacy as a magic bullet. Regardless of one's critique of synthetic beta-carotene and the other pitfalls of recent carotenoid research, I'd argue that we've seen all too clearly in the CARET and similar studies the danger of selecting one nutrient from amongst a broad family of nutrients (alpha-carotene, gammacarotene, lutein, lycopene, canthaxanthin, fucoxanthin, etc.) and hoping for the best. Heart attack is a good reason for intervening with an isolated nutrient. But when we think about preventive nutrition, and the principles of nutritional support, we have to return to food and its evolutionary-based composition of nutrients. To my knowledge, there has not been one single natural-foods-based intervention to date in any area of chronic disease prevention which has yielded negative results. While we are experimenting with NAC in emergency cardiovascular medicine, let's look further into naturally occurring forms of sulfur in food, and the relationship of these forms to human sulfur metabolism.

Natural Product Research Consultants, Inc.

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By B. Levin

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