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(Circulation. 1998;97:736-743.)
© 1998 American Heart Association, Inc.

Clinical Investigations and Reports

Coronary Artery Responses to Physiological Stimuli Are Improved by Deferoxamine but not by L-Arginine in Non–Insulin-Dependent Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Risk Factors

Alain Nitenberg, MD; Frédéric Paycha, MD; Séverine Ledoux, MD; Régis Sachs, MD; Jean-Raymond Attali, MD; ; Paul Valensi, MD

From the Service de Physiologie et d'Explorations Fonctionnelles, INSERM, Hôpital Louis Mourier, CHU Xavier-Bichat, Colombes, France (A.N., F.P., S.L.), and Service d'Endocrinologie Diabetologue et Nutrition, Hôpital Jean Verdier, Bondy, France (R.S., J-R.A., P.V.).

Correspondence to Alain Nitenberg, MD, Service de Physiologie et d'Explorations Fonctionnelles, INSERM U.426, Hôpital Louis Mourier, CHU Xavier-Bichat, 178, rue des Renouillers, F-92700 Colombes, France.

Abstract

Background—Acetylcholine produces coronary artery (CA) constriction in diabetic patients, suggesting an impairment of endothelium-dependent dilation. In diabetes, multiple metabolic abnormalities may inactivate nitric oxide through oxygen free radical production.

Methods and Results—To examine the mechanism of this abnormal response, two physiological tests (ie, a cold pressor test [CPT] and coronary flow increase induced by an injection of 10 mg papaverine [PAP] in the distal left anterior descending CA) were performed before and after either intravenous L-arginine (625 mg/minx10 minutes) or intravenous deferoxamine (50 mg/minx10 minutes) in 22 normotensive nonsmoking diabetic patients with angiographically normal CAs and normal cholesterol. Coronary surface areas were measured with quantitative angiography. Before the administration of L-arginine or deferoxamine, CPT induced CA constriction in both groups (-14±10% and -15±11%, respectively; each P<.001), and PAP injection in distal LAD did not modify significantly proximal LAD dimensions. In the 10 diabetic patients receiving L-arginine, responses to CPT and PAP were not modified. Conversely, in the 12 patients receiving deferoxamine, CA dilated in response to the two tests (+10±9% after CPT and +22±7% after PAP, each P<.001). Intracoronary isosorbide dinitrate, an endothelium-independent dilator, produced similar dilation in the two groups (+47±19% and +41±15%, respectively; each P<.001).

Conclusions—This study shows that (1) responses of angiographically normal CAs to CPT and to flow increase are impaired in diabetic patients; (2) abnormal responses are not improved by L-arginine, suggesting that a deficit in substrate for nitric oxide synthesis is not involved; and (3) deferoxamine restores a vasodilator response to the two tests, suggesting that inactivation of NO by oxygen species might be partly responsible for the impairment of CA dilation in diabetic patients.

Key Words: antioxidants • coronary disease • diabetes mellitus • free radicals

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