Effects of exogenous oxygen derived free radicals on myocardial capillary permeability, vascular tone, and incidence of ventricular arrhythmias in the canine heart.

Abstract

The aim was to examine the effects of exogenous oxygen derived free radicals on myocardial capillary permeability for a small hydrophilic indicator, postischaemic vascular tone, and the occurrence of arrhythmias in the canine heart in vivo. Free radicals were generated by simultaneous intracoronary infusion of hypoxanthine and xanthine oxidase into normally perfused myocardium, and at reperfusion following five minutes of coronary occlusion, respectively, in 20 anaesthetised open chest dogs. Myocardial capillary extraction for 99mTc-DTPA, plasma flow rate, and the interstitial washout rate constant were measured by the single injection, residue detection method, and the capillary permeability-surface area product (PS) was calculated. The maximum plasma flow during reactive hyperaemia was measured by the local 133Xe washout method. Hypoxanthine and xanthine oxidase infusion into normally perfused myocardium induced a 15% decrease in capillary extraction (p = 0.05), a 24% decrease in PS (p < 0.01), and a 23% decrease in the interstitial washout rate constant (NS) two minutes after the end of the infusion. When hypoxanthine and xanthine oxidase were infused into postischaemic myocardium, 86% of animals developed sustained ventricular arrhythmias, in contrast to none in control experiments (p < 0.05). The maximum plasma flow was 363% of preocclusive values in control experiments v 268% in hypoxanthine + xanthine oxidase experiments (p < 0.05). In normally perfused hearts, intracoronary infusion of hypoxanthine and xanthine oxidase induce a decreased capillary extraction, suggesting a reduced capillary surface area. In postischaemic myocardium these substances cause a decreased vasodilatation in the initial phase of reactive hyperaemia, and induce ventricular arrhythmias.