Endothelium-dependent and -independent perfusion reserve and the effect of L-arginine on myocardial perfusion in patients with syndrome X

Abstract

Background - Impaired vasodilatation capacity in patients with angina pectoris and a normal coronary arteriogram (syndrome X [SX]) has been reported. Most studies report on the response in epicardial vessels. This does not necessarily reflect compromised myocardial microcirculation. Lack of the NO precursor L-arginine has been suggested as a possible cause. Methods and Results - Myocardial blood flow (MBF) was measured, using PET, at rest (MBF-rest) and during intravenous dipyridamole (MBF-DIP) in 25 women (mean age 53 ± 7 years) with SX. Thirty healthy volunteers served as controls. One group (A) consisted of 15 age-matched female volunteers (54 ± 10 years). The other control group consisted of 15 young healthy women (B; 24 ± 5 years). In 12 SX patients, MBF-rest and MBF during cold pressor testing were also measured after infusion of L-arginine (6.7 g/min for 45 minuteS). The increase in MBF after cold pressor testing was similar in the SX group compared with controls. L-arginine did not affect MBF-rest (0.83 ± 0.14 versus 0.89 ± 0.13 mL · g-1 · min-1) or MBF after cold pressor test (0.95 ± 0.10 versus 1.03 ± 0.17 mL · g-1 min-1). In contrast, the hyperemic response to DIP was blunted compared with the group A controls (1.68 ± 0.49 versus 2.34 ± 0.45 mL · g-1 · min-1, P<0.05); this resulted in a significant reduction of the coronary flow reserve in SX patients relative to controls (2.03 ± 0.53 versus 2.96 ± 0.63 mL · g-1 · min-1, P<0.01). Conclusions - In patients with SX, the microcirculatory response to cold, reflecting the endothelium function, is normal and unaltered by intravenous L-arginine. This suggests preserved microcirculatory endothelial function. However, a markedly attenuated hyperemic flow and flow reserve after DIP suggest a dysfunction of the adenosine-mediated endothelium-independent vasodilatation at the microcirculatory level in these patients.