Myocardial alterations due to free-radical generation

Abstract

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. However, the exact types of damage that result from myocardial exposure to free radicals remains to be established. 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 microM Fe3+-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 function.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial reperfusion: a double-edged sword?

“…Secondly, during myocardial ischemia, there is loss ofthe enzymes, superoxide dismutase, catalase, and glutathione peroxidase (47, 5 1), which could protect the heart from oxygen-derived free radicals. The autoxidation of catecholamines could provide another source of free radicals (52,53).…”

Direct measurement of free radical generation following reperfusion of ischemic myocardium.

“…It has been proposed that a major portion of this reflow injury occurs secondary to the generation of oxygen free radicals (5). During the past decade indirect evidence from studies demonstrating the protective effects of free radical scavengers has suggested that reactive free radicals are formed both during ischemia and, more importantly, during postischemic reperfusion (5)(6)(7)(8)(9)(10). Also, reactive oxygen radicals have been shown to produce myocardial damage (6).…”

Synthesis and In-Vitro Antioxidant Study Of 5, 6-O, O-Diacetyl-2, 3-O, O-Dibenzyl-L-Ascorbic Acid

“…All the ascorbic acid derivatives were characterized by 1 C NMR spectra were recorded on a Varian Gemini 300 spectrometer, operating at 75.46 MHz for the 13 C resonance. The samples were dissolved in DMSO-d 6 or CDCl 3 chemical shift values are in ppm, referred to TMS.…”