Laycock S K, McMurray J, Kane K A, Parratt J R
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
Free Radic Biol Med. 1993 Sep;15(3):249-55. doi: 10.1016/0891-5849(93)90071-2.
This investigation aimed to determine whether contractile dysfunction of the myocardium could be produced upon generation of free radicals in the anaesthetised rat. The enzyme xanthine oxidase, combined with its substrate purine and an iron source, was used to generate free radicals in the venous circulation. The suspended form of xanthine oxidase, with substrate, produced a transient, significant depression in the contractile indices dP dt-1 max and dP dt-1 P-1 and arterial blood pressure, 1146 +/- 87 mm Hg s-1, 9 +/- 1 s-1, and 18 +/- 1 mm Hg, respectively. This could not be attenuated by the enzymatic free radical scavengers superoxide dismutase and catalase. Furthermore, the suspended xanthine oxidase alone or its vehicle were able to produce a similar effect to that of the complete free-radical-generating system. The maximum soluble dose of the crystalline form of the enzyme when employed in the generating system had no effect upon administration despite its production of superoxide radicals in vitro. These results suggest that the haemodynamic effects of the free-radical-generating system containing the suspended form of xanthine oxidase were due to the effects of its vehicle and that the free-radical-generating system containing the crystalline form of the enzyme did not produce sufficient free radicals in vivo to modify myocardial contractility.
本研究旨在确定在麻醉大鼠体内产生自由基时，心肌收缩功能障碍是否会出现。黄嘌呤氧化酶与底物嘌呤及铁源相结合，用于在静脉循环中产生自由基。悬浮形式的黄嘌呤氧化酶及其底物会使收缩指标dP dt-1 max和dP dt-1 P-1以及动脉血压分别出现短暂且显著的下降，分别为1146 +/- 87 mmHg s-1、9 +/- 1 s-1和18 +/- 1 mmHg。这种情况无法被酶促自由基清除剂超氧化物歧化酶和过氧化氢酶减弱。此外，单独的悬浮黄嘌呤氧化酶或其溶剂能够产生与完整自由基生成系统类似的效果。当在生成系统中使用该酶的结晶形式的最大可溶剂量时，尽管其在体外会产生超氧自由基，但给药后并无效果。这些结果表明，含有悬浮形式黄嘌呤氧化酶的自由基生成系统的血流动力学效应是由于其溶剂的作用，且含有该酶结晶形式的自由基生成系统在体内并未产生足够的自由基来改变心肌收缩力。
