Coronary microvascular adaptation to myocardial metabolic demand can be restored by inhibition of iron-catalyzed formation of oxygen free radicals in type 2 diabetic patients

Abstract

Dilation of coronary vessels is impaired in diabetic patients when myocardial metabolic demand is increased. Deferoxamine (DFX) restores a normal dilation of epicardial coronary arteries. To assess the effects of DFX on metabolic coronary microvascular dilation in type 2 diabetic patients, coronary blood flow was measured using intracoronary Doppler and quantitative angiography in 17 type 2 diabetic patients with normal coronary arteries and without any other coronary risk factors. Measurements were made at baseline and during a cold pressor test (CPT), before and after intravenous administration of DFX. With a similar rate-pressure product (RPP) increase during CPT before and after DFX (+21.1 ± 8.7 vs. +20.5 ± 8.9%, respectively), coronary blood flow increase was significantly enhanced after DFX (+31.8 ± 16.7 vs. +6.3 ± 12.9% before DFX, P < 0.001). Moreover, coronary resistance increased during CPT before DFX and decreased after DFX (+14.8 ± 21.9 vs. -7.9 ± 10.9%, respectively, P < 0.001). Lastly, the negative relationship between coronary blood flow and RPP before DFX (R = 0.546, P < 0.05) was changed in a positive relationship after DFX (R = 0.518, P < 0.05). In conclusion, in type 2 diabetic patients, inhibition of iron-catalyzed oxidative reactions by DFX restored dilation of the coronary microcirculation and a normal matching between myocardial metabolic demand and coronary blood flow.