Critical coronary stenosis
Lee, Paul Man-Yiu
Coronary arterial stenosis causes impairment of cardiac function and is the major contributor of mortality in cardiovascular disease. The data to date suggest that coronary stenosis greater than 50% is considered significant. Consequently, stenotic conditions of less than 50% are usually disregarded by the medical profession. However, myocardial ischemia may occur with less than 50% occlusion to the coronary artery. Ischemia leads to the accumulation of xanthine oxidase and xanthine. The conversion of xanthine into uric acid in the presence of xanthine oxidase leads to the production of oxygen free radicals (OFRs) which causes oxidative damage. Increase in levels of OFRs may affect the levels of antioxidants and could damage cell membranes, thereby producing malondialdehyde (MDA). It is hypothesized that ischemia would produce changes in the antioxidant reserve and the production of MDA. Critical coronary stenosis would be defined as the degree of stenosis at which significant changes in ischemia-related oxidative stress (antioxidant reserve and/or MDA) will first be apparent. To verify this hypothesis, experiments were conducted to investigate the effects of various degrees of stenosis (0, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79 and 100%) of the anterior descending branch of the left coronary artery on the antioxidant reserve (an increase in antioxidant reserve suggests a decrease in tissue chemiluminescence and vice-versa), activities of various enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and catalase), and MDA levels in cardiac muscle in anaesthetized dogs. ECGs were also monitored for comparison purposes. A significant increase in tissue chemiluminescence was observed with as little as 20-29% stenosis of the coronary artery. This increase in tissue chemiluminescence suggests that the myocardium was undergoing oxidative stress and it was reflected by a decrease in the antioxidant reserve. The initial decrease in the antioxidant reserve was found to be non-enzymatic in nature because no decrease in the enzymatic antioxidant levels were observed accompanying the increase in tissue chemiluminescence. Furthermore, at 20-29% stenosis a significant increase in mitochondrial Mn-SOD was found suggesting oxidative stress at the mitochondrial level. An increase in catalase activity was also observed at this level of stenosis. MDA level, however, was elevated beginning at 50-59% of stenosis. This suggests that tissue damage occurred at levels of stenosis greater than 50%. Ischemic ECG changes appeared at the level of stenosis greater than 50%. These results suggest that biochemical parameters related to ischemia were evident at 20-29% of coronary artery stenosis. In conclusion, therefore, critical coronary stenosis should be defined at 20-29% of coronary stenosis.