Syndrome X and endothelial dysfunction.
OBJECTIVE
Syndrome X (angina, normal coronary arteriogram and positive exercise test) remains an enigma with unexplained features and apparent conflicts of evidence. The present study addressed whether (i) the Syndrome is characterised by generalised flow-related endothelial dysfunction, (ii) myocardial thallium201 defects reflect myocardial or microvascular dysfunction, (iii) endothelial dysfunction and its consequences can be improved by oral L-arginine.


METHODS
Flow-mediated brachial artery dilatation was measured by ultrasonic 'wall-tracking' in 7 Syndrome X patients, further characterised as having thallium201 defects and no known cause of endothelial dysfunction, and a normal control group. Syndrome X patients entered a 4-week randomised double-blind placebo-controlled cross-over trial of oral L-arginine (7 g twice daily), with brachial artery studies, exercise tests and technetium99 tetrafosmin scans.


RESULTS
Flow-mediated dilatation was absent in Syndrome X vs. normal. Stress technetium99 tetrafosmin and thallium201 scans showed similar defects. Flow-mediated dilatation, symptom-limited exercise duration and peak oxygen consumption (VO2max) were increased but rate-pressure-product (RPP) and radionuclide defects were unchanged after L-arginine vs. placebo.


CONCLUSIONS
The study supports coronary microvascular rather than myocardial dysfunction and shows loss of flow-mediated dilatation in systemic arteries. Oral L-arginine improved flow-mediated dilatation, exercise capacity and VO2max (by ca. 17%) despite unchanged RPP. The findings support generalised endothelial dysfunction. The arginine effects imply NO-mediated improvement of skeletal muscle perfusion suggesting improved homogeneity of microvascular distribution.
Bellamy
M F
MF
Department of Cardiology, University of Wales College of Medicine, Cardiff, UK.
Goodfellow
J
J
Tweddel
A C
AC
Dunstan
F D
FD
Lewis
M J
MJ
Henderson
A H
AH
D000284:Administration, Oral; D001120:Arginine / Q000627:therapeutic use*; D001916:Brachial Artery / Q000000981:diagnostic imaging; D003326:Coronary Circulation; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005080:Exercise Test; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008833:Microcirculation; D017566:Microvascular Angina / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D008875:Middle Aged; D015609:Organotechnetium Compounds; D010101:Oxygen Consumption / Q000187:drug effects; D011877:Radionuclide Imaging; D012039:Regional Blood Flow; D013794:Thallium Radioisotopes; D014463:Ultrasonography; D014664:Vasodilation
D015609:Organotechnetium Compounds; D013794:Thallium Radioisotopes; D001120:Arginine