Increased Production of Oxygen Free Radicals by Polymorphonuclear Leukocytes in Heart Failure Due to Aortic Stenosis

Abstract

Oxygen free radicals have been linked to a wide variety of cellular damage in biological systems. Poly morphonuclear (PMN) leukocytes stimulation is one of the known sources for oxygen free radicals. It has been suggested that oxygen free radicals depress the excitation-con traction coupling in cardiac muscle. It is possible that a decrease in the myocardial contractility in heart fail ure might be due to an increased oxy gen-free-radical-producing activity of PMN leukocytes. The authors studied, therefore, the release of oxy gen free radicals, as measured by luminol-dependent chemilumines cence activity, from the PMN leuko cytes in dogs with heart failure due to aortic stenosis. Hemodynamics and phagocytic activity of PMN leuko cytes were studied in 6 control dogs and 6 dogs with aortic stenosis of six to nine months' duration. There was a significant decrease in the index of myocardial contractility and an in crease in the left ventricular end- diastolic pressure in dogs with aortic stenosis, suggesting left ventricular failure in these dogs. Although there was a tendency for a decrease in the cardiac index in dogs with aortic stenosis, the decrease was not signifi cant. Phagocytic activity of PMN leu kocytes in blood was studied in con trol dogs and dogs with aortic steno sis. Phagocytosis was initiated by ad dition of opsonized zymosan and chemiluminescence was monitored by use of a luminometer. The peak chemiluminescence activity of the PMN leukocytes in blood of dogs with heart failure was about threefold greater than that in the blood from control dogs. The presence of super oxide dismutase, a scavenger of oxy gen free radicals, reduced the chemi luminescence from PMN leukocytes in both the control dogs and dogs with aortic stenosis. These results suggest that the increased production of oxygen free radicals by PMN leu kocytes might contribute to a de crease in the myocardial contractility and, hence, to heart failure in dogs with aortic stenosis.