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Oxygen free radicals and myocardial damage: protective role of thiol-containing agents
- Source :
- The American journal of medicine. 91(3C)
- Publication Year :
- 1991
-
Abstract
- It has been suggested that the sudden presence of oxygen during reperfusion after a period of ischemia may be toxic for the myocardial cell. The oxygen molecule is capable of producing reactions in the cell, forming highly reactive free radicals, and inducing lipid peroxidation of membranes, altering their integrity and increasing their fluidity and permeability. The ischemic and reperfused cardiac cell is the prime candidate for this reaction sequence and may explain the molecular mechanism underlying the pathologic events related to membrane dysfunction and calcium homeostasis. However, the myocardium has a series of defense mechanisms including the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase plus other endogenous antioxidants such as vitamin E, ascorbic acid, and cysteine to protect the cell against the cytotoxic oxygen metabolites. The prerequisite for oxygen free radical involvement in ischemia and reperfusion damage is that ischemia alters the defense mechanisms against oxygen toxicity. It is known that ischemia may impair mitochondrial SOD and, with reperfusion, oxidative stress may occur as shown by tissue accumulation and release of oxidized glutathione. This tripeptide molecule in the cofactor of glutathione peroxidase, the enzyme that removes hydrogen and lipid peroxides. Its formation and subsequent release is a reliable index of oxidative damage. In our study, we investigated the effects of N-acetylcysteine on oxidative damage in the isolated rabbit heart. N-acetylcysteine increases, in a dose-dependent manner (from 10(-7) to 10(-5) M), the myocardial glutathione content and provides an important degree of protection against ischemia and reperfusion. Oxidative stress does not occur, mitochondrial function is maintained, enzyme release is reduced, and contractile recovery is increased. Similarly, we administered N-acetylcysteine in the pulmonary artery of coronary artery disease patients undergoing coronary bypass grafting (150 mg/kg in 1 hour followed by 150 mg/kg in 4 hours). The degree of oxidative stress on reperfusion was reduced and recovery of cardiac function improved. In this article, we review the cardioprotective role of thiol-containing agents.
- Subjects :
- medicine.medical_specialty
Antioxidant
Free Radicals
Neutrophils
medicine.medical_treatment
Coronary Disease
Myocardial Reperfusion Injury
Pharmacology
medicine.disease_cause
Models, Biological
Antioxidants
Lipid peroxidation
Superoxide dismutase
chemistry.chemical_compound
medicine
Animals
Humans
Sulfhydryl Compounds
Oxygen toxicity
Free-radical theory of aging
chemistry.chemical_classification
biology
business.industry
Glutathione peroxidase
Myocardium
General Medicine
Glutathione
medicine.disease
Oxidants
Surgery
Oxygen
chemistry
biology.protein
business
Oxidative stress
Subjects
Details
- ISSN :
- 00029343
- Volume :
- 91
- Issue :
- 3C
- Database :
- OpenAIRE
- Journal :
- The American journal of medicine
- Accession number :
- edsair.doi.dedup.....38ee303fcfc1c3aabf217ec3ac36cf0d