Inhibition of iron-catalyzed oxidative reactions restores matching betweencoronary blood flow and myocardial metabolic demand

In diabetes, endothelium-dependent dilation of large and small coronary art eries is impaired, which results in a mismatch between myocardial metabolic demand and coronary blood flow. It has been proved that deferoxamine, an i ron chelator that inhibits Fenton and Haber-Weiss reactions, restores a nor mal response to cold pressor test and flow increase in angiographically nor mal epicardial coronary arteries of diabetic patients. This result suggests that nitric oxide could be inactivated by reactive oxygen species. The aim of this study was to assess the effects of deferoxamine on coronary microc irculation vasomotion when myocardial oxygen demand is increased by sympath etic stimulation elicited by cold pressor test in type 2 diabetic patients. In 17 patients with angiographically normal coronary arteries and without a ny other coronary risk factors, coronary blood flow has been measured using quantitative angiography and intracoronary Doppler at baseline and during a cold pressor test, before and after intravenous administration of 500 mg deferoxamine. Increase in rate-pressure product, an estimate of myocardial metabolic demand, was similar before and after deferoxamine (+21.1 +/-8.7% vs +20.5 +/-8.9%, respectively), but coronary blood flow increase was signi ficantly higher after deferoxamine (+6.3 +/- 12.9% vs +31.8 +/- 16.7%, resp ectively, p<0.001), and coronary resistance was increased before deferoxami ne and decreased after (+14.8<plus/minus>21.9% vs -7.9 +/- 10.9%, respectiv ely, p<0.001). Moreover, before deferoxamine, the negative correlation betw een coronary blood flow and rate-pressure product changes before deferoxami ne (R=0.518, P<0.05) was turned in a positive relationship after deferoxami ne (r=0.546, p<0.05). In conclusion, in type 2 diabetic patients, endothelium-dependent dilation of the coronary micro circulation is restored when iron-catalysed oxidative reactions are inhibited by deferoxamine, which restores the normal matchin g between myocardial oxygen demand and coronary blood flow.