EFFECTS OF THE XANTHINE-OXIDASE SYSTEM ON CARDIAC-FUNCTION IN ANESTHETIZED RATS

This investigation aimed to determine whether contractile dysfunction of the myocardium could be produced upon generation of free radicals i n the anaesthetised rat. The enzyme xanthine oxidase, combined with it s substrate purine and an iron source, was used to generate free radic als in the venous circulation. The suspended form of xanthine oxidase, with substrate, produced a transient, significant depression in the c ontractile indices dP dt-1 max and dP dt-1 P-1 and arterial blood pres sure, 1146 +/- 87 mm Hg s-1, 9 +/- 1 s-1, and 18 +/- 1 mm Hg, respecti vely. This could not be attenuated by the enzymatic free radical scave ngers superoxide dismutase and catalase. Furthermore, the suspended xa nthine oxidase alone or its vehicle were able to produce a similar eff ect to that of the complete free-radical-generating system. The maximu m soluble dose of the crystalline form of the enzyme when employed in the generating system had no effect upon administration despite its pr oduction of superoxide radicals in vitro. These results suggest that t he haemodynamic effects of the free-radical-generating system containi ng the suspended form of xanthine oxidase were due to the effects of i ts vehicle and that the free-radical-generating system containing the crystalline form of the enzyme did not produce sufficient free radical s in vivo to modify myocardial contractility.