Induction of necrosis and failure in the isolated perfused rat heart with oxidized isoproterenol

Abstract

The effects of fresh and oxidized isoproterenol (100 mg/l) on mechanical function and ultrastructure of the isolated perfused rat heart were studied. In contrast to fresh isoproterenol, isoproterenol oxidized for 6 to 8 h decreased developed contractile tension, maximum rate of tension development and maximum rate of relaxation. The hearts perfused with oxidized isoproterenol were unable to generate contractile force in about 35 min, and showed a marked increase in resting tension. Although fresh isoproterenol at high concentrations employed in this study did not show an increase in the developed contractile force, the maximum rates of tension development and relaxation were increased in comparison to the control. Both fresh and oxidized isoproterenol decreased times for peak tension and for 1 2 relaxation. The hearts perfused with oxidized isoproterenol, but not with fresh isoproterenol, showed disrupted myofilaments, swollen mitochondria and other ultrastructural damage which is commonly seen in myocardial necrosis. The ability of the solution of isoproterenol oxidized for 16 to 24 h to depress cardiac function and induce necrosis was markedly less than that of the one oxidized for 6 to 8 h. These results are consistent with the view that oxidized products of catecholamines, but not catecholamines per se, are responsible for inducing myocardial necrosis and failure.