Oxidative stress in the human heart is associated with changes in the antioxidative defense as shown after heart transplantation

The study was designed to demonstrate - for the first time in humans - that oxidative stress in the heart indicated by lipid peroxidation is associated with time--dependent changes in the enzymatic antioxidative defense. For this purpose, we analyzed the oxygen radical metabolism in 69 myocardial biopsies (taken between the fifth day and 6 years after transplantation) of 31 heart transplant recipients who were suspected of suffering from increased formation of oxygen radicals in the allograft. The levels of lipid peroxides (LPO), glutathione peroxidase (GSH-Px), total-, copper/zinc- and manganese superoxide dismutase (t-SOD, CuZnSOD, MnSOD) were compared in 3 post-transplantation periods (5-90 d vs. 91-365 d vs. 1 y). Significantly increased LPO levels were found (0.27 +/- 0.04 vs. 0.13 +/- 0.02 vs. 0.27 +/- 0.04 nmol/mg protein) in the first and third period. Increased activities of GSH-Px (39.8 +/- 3.8 vs. 30.2 +/- 4.1 vs. 76.+/- 6.5 mU/mg protein), t-SOD (1.57 +/- 0.10 vs. 1.30 +/- 0.14 vs. 2.44 +/- 0.23 U/mg protein) and CuZnSOD (1.09 +/- 0.08 vs. 0.93 +/- 0.13 vs. 2.05 +/- 0.21 U/mg protein) occurred only in the third period. For calculation of time courses more precisely, the single data with respect to time were analyzed with a curve fitting program. Except for the first period, the allograft LPO and GSH-Px levels rose for up to 6 years after transplantation. However, the t-SOD and CuZnSOD activities switched from increase to decrease in the third period. The study provided indication for: first, the potency of the human heart to time-limited increase of the enzymatic antioxidative defense, and secondly, the inability of human heart allografts - despite this adaptation - for complete prevention of myocardial oxidative stress.