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 associate d with time--dependent changes in the enzymatic antioxidative defense. For this purpose, we analyzed the oxygen radical metabolism in 69 myocardial bi opsies (taken between the fifth day and 6 years after transplantation) of 3 1 heart transplant recipients who were suspected of suffering from increase d 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. I ncreased 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 respec t 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 tr ansplantation. However, the t-SOD and CuZnSOD activities switched from incr ease 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 c omplete prevention of myocardial oxidative stress.