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.
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.
Nitenberg
Alain
A
Department of Physiology and Functional Investigations, University Xavier-Bichat, Colombes, France. alain.nitenberg@jvr.ap-hop-paris.fr
Ledoux
Séverine
S
Valensi
Paul
P
Sachs
Régis
R
Antony
Isabelle
I
D001783:Blood Flow Velocity; D001794:Blood Pressure; D003080:Cold Temperature; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology*; D003676:Deferoxamine / Q000008:administration & dosage; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate; D006801:Humans; D007501:Iron / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000008:administration & dosage; D008297:Male; D008833:Microcirculation / Q000503:physiopathology*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000737:chemistry*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D007501:Iron; D003676:Deferoxamine