Myocardial alterations due to free-radical generation
Oxygen-derived free radicals have been proposed as general mediators of tissue injury in a variety of disease states. Recent interest has focused on the possibility that free radicals may be involved in ischemic myocardial damage. The purpose of this study was to evaluate the effects of superoxide and hydroxyl radicals on myocardial structure and function in an isolated perfused rabbit interventricular septal preparation. Superoxide was generated by adding purine (2.3 mM) and xanthine oxidase (0.01 U/ml) to the physiological solutions perfusing the septa. Hydroxyl radical generation was catalyzed by the addition of 2.4 ..mu..M Fe/sup 3 +/-loaded transferrin to the system. Exposure of normal septa to superoxide-generating solutions resulted in the development of structural alterations in the vascular endothelium including the development of vacuoles. Membranous cellular debris was evident in the extracellular space and within the vessels. Cardiac myocytes showed evidence of mild alterations. Exposure of septa to solutions capable of generating hydroxyl radicals resulted in more extensive and severe damage. Vascular endothelial cells showed evidence of vacuoles or blebs and edema. Severe swelling of mitochondria was evident in cardiac myocytes and vascular endothelial cells. In addition, myocytes often showed blebbing of the basement membrane. Normal septa exposed to superoxide showed no significant decrease in developed tension, whereas hydroxyl radical exposure resulted in a significant decrease in myocardial functions. Addition of superoxide dismutase to the solutions perfusing the septa protected against myocardial alterations. Thus oxygen-derived free radicals, when generated in the heart, are capable of causing significant myocardial injury.
- Research Organization:
- Univ. of Texas Health Science Center, Dallas
- OSTI ID:
- 5742305
- Journal Information:
- Am. J. Physiol.; (United States), Vol. 246:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HYDROXYL RADICALS
BIOLOGICAL EFFECTS
MYOCARDIUM
ULTRASTRUCTURAL CHANGES
SUPEROXIDE RADICALS
ENDOTHELIUM
INJURIES
MITOCHONDRIA
PERFUSED ORGANS
RABBITS
SUPEROXIDE DISMUTASE
ANIMAL TISSUES
ANIMALS
BODY
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
ENZYMES
HEART
MAMMALS
MORPHOLOGICAL CHANGES
MUSCLES
ORGANOIDS
ORGANS
OXIDOREDUCTASES
RADICALS
TISSUES
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)