Nitenberg A, Ledoux S, Valensi P, Sachs R, Antony I
Service de physiologie et d'explorations fonctionnelles, hôpital Louis-Mourier, CHU Xavier-Bichat, Colombes.
Arch Mal Coeur Vaiss. 2001 Aug;94(8):775-8.
In diabetes, endothelium-dependent dilation of large and small coronary arteries is impaired, which results in a mismatch between myocardial metabolic demand and coronary blood flow. It has been proved that deferoxamine, an iron chelator that inhibits Fenton and Haber-Weiss reactions, restores a normal response to cold pressor test and flow increase in angiographically normal 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 microcirculation vasomotion when myocardial oxygen demand is increased by sympathetic stimulation elicited by cold pressor test in type 2 diabetic patients. In 17 patients with angiographically normal coronary arteries and without any 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 significantly higher after deferoxamine (+6.3 +/- 12.9% vs +31.8 +/- 16.7%, respectively, p < 0.001), and coronary resistance was increased before deferoxamine and decreased after (+14.8 +/- 21.9% vs -7.9 +/- 10.9%, respectively, p < 0.001). Moreover, before deferoxamine, the negative correlation between coronary blood flow and rate-pressure product changes before deferoxamine (R = 0.518, P < 0.05) was turned in a positive relationship after deferoxamine (r = 0.546, p < 0.05). In conclusion, in type 2 diabetic patients, endothelium-dependent dilation of the coronary microcirculation is restored when iron-catalysed oxidative reactions are inhibited by deferoxamine, which restores the normal matching between myocardial oxygen demand and coronary blood flow.
在糖尿病患者中，大、小冠状动脉的内皮依赖性舒张功能受损，这导致心肌代谢需求与冠状动脉血流之间不匹配。业已证明，去铁胺这种抑制芬顿反应和哈伯-维伊斯反应的铁螯合剂，可使糖尿病患者造影显示正常的心外膜冠状动脉对冷加压试验和血流增加恢复正常反应。这一结果表明，一氧化氮可能被活性氧灭活。本研究的目的是评估在2型糖尿病患者中，通过冷加压试验引发交感神经刺激使心肌需氧量增加时，去铁胺对冠状动脉微循环血管运动的影响。对17例冠状动脉造影正常且无任何其他冠状动脉危险因素的患者，在静脉注射500mg去铁胺之前和之后，于基线状态及冷加压试验期间，使用定量血管造影术和冠状动脉内多普勒测量冠状动脉血流。去铁胺用药前后，作为心肌代谢需求估计值的心率-血压乘积增加相似（分别为+21.1±8.7%和+20.5±8.9%），但去铁胺用药后冠状动脉血流增加显著更高（分别为+6.3±12.9%和+31.8±16.7%，p<0.001），且冠状动脉阻力在去铁胺用药前增加，用药后降低（分别为+14.8±21.9%和-7.9±10.9%，p<0.001）。此外，在去铁胺用药前，冠状动脉血流与去铁胺用药前心率-血压乘积变化之间呈负相关（R=0.518，P<0.05），而在去铁胺用药后转为正相关（r=0.546，p<0.05）。总之，在2型糖尿病患者中，当去铁胺抑制铁催化的氧化反应时，冠状动脉微循环的内皮依赖性舒张功能得以恢复，从而恢复心肌需氧量与冠状动脉血流之间的正常匹配。
