SYNDROME-X AND ENDOTHELIAL DYSFUNCTION

Objective: Syndrome X (angina, normal coronary arteriogram and positiv e exercise test) remains an enigma with unexplained features and appar ent conflicts of evidence. The present study addressed whether (i) the Syndrome is characterised by generalised flow-related endothelial dys function, (ii) myocardial thallium(201) defects reflect myocardial or microvascular dysfunction, (iii) endothelial dysfunction and its conse quences can be improved by oral L-arginine. Methods: Flow-mediated bra chial artery dilatation was measured by ultrasonic 'wall-tracking' in 7 Syndrome X patients, further characterised as having thallium(201) d efects and no known cause of endothelial dysfunction, and a normal con trol group. Syndrome X patients entered a 4-week randomised double-bli nd placebo-controlled cross-over trial of oral L-arginine (7 g twice d aily), with brachial artery studies, exercise tests and technetium(99) tetrafosmin scans. Results: Flow-mediated dilatation was absent in Sy ndrome X vs. normal. Stress technetium(99) tetrafosmin and thallium(20 1) scans showed similar defects. Flow-mediated dilatation, symptom-lim ited exercise duration and peak oxygen consumption (VO2max) were incre ased but rate-pressure-product (RPP) and radionuclide defects were unc hanged after L-arginine vs. placebo. Conclusions: The study supports c oronary microvascular rather than myocardial dysfunction and shows los s of flow-mediated dilatation in systemic arteries. Oral L-arginine im proved flow-mediated dilatation, exercise capacity and VO2max (by ca. 17%) despite unchanged RPP. The findings support generalised endotheli al dysfunction. The arginine effects imply NO-mediated improvement of skeletal muscle perfusion suggesting improved homogeneity of microvasc ular distribution. (C) 1998 Elsevier Science B.V. All rights reserved.