SummaryBackground: Myocardial bridging (MB) has been associated with cardiac events. Whether coronary spasm is one factor contributing to those events is unknown.Hypothesis: This study investigated whether the likelihood of coronary spasm is increased in patients with MB.Methods: A spasm-provocation test was performed by infusing acetylcholine into the left coronary artery in 114 Japanese patients with chest pain. The test result was defined as positive when the diameter of the coronary artery was reduced by ≥ 50% and ST-segment changes were documented. Myocardial bridging was defined as a > 15% reduction in coronary arterial diameter during systole after intracoronary injection of nitroglycerin.Results: Myocardial bridging was identified in 41 patients (36%) and was located in the mid-segment of the left anterior descending coronary artery (LAD) in all patients. Patients with MB experienced coronary spasm more frequently than patients without MB (MB+: 73%; MBϪ: 40%, p = 0.0006). Furthermore, among patients with a positive spasm-provocation test, coronary spasm occurred more frequently in the midsegment of the LAD in patients with MB than in those without MB (MB+: 73%; MBϪ: 45%, p = 0.0259). Multivariate regression analysis demonstrated that MB was a predictor of coronary spasm (odds ratio: 3.478, p = 0.0088).

Objective: To examine the effect of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase, on coronary artery endothelial function in hypercholesterolaemic patients. Design: Quantitative coronary angiography and Doppler flowmetry were used to examine the effects of intracoronary infusion of BH4 on vascular response to acetylcholine (ACh). Setting: Tertiary cardiology centre. Patients: 18 patients with angiographically normal coronary arteries, of whom nine had hypercholesterolaemia and nine had noromocholesterolaemia. Interventions: ACh (3 and 30 µg/min) was infused for two minutes into the left coronary ostium. ACh was then simultaneously infused with BH4 (1 mg/min) before and after infusion of L-N G -monomethyl-Larginine (L-NMMA) (40 µmol/min for five minutes). Main outcome measures: Diameter of the epicardial coronary arteries and coronary blood flow. Results: In hypercholesterolaemic patients, BH4 attenuated the ACh induced decrease in coronary diameter (p < 0.05) and restored the ACh induced increase in coronary blood flow (p < 0.05). In normocholesterolaemic patients, BH4 did not affect the ACh induced changes in coronary diameter or coronary blood flow. In both groups, L-NMMA decreased the baseline coronary diameter (p < 0.05) and baseline coronary blood flow (p < 0.05). In hypercholesterolaemic patients, L-NMMA inhibited both the BH4 mediated attenuation of the ACh induced decrease in coronary diameter (p < 0.05) and the BH4 mediated enhancement of the ACh induced increase in coronary blood flow (p < 0.01). Conclusions: Intracoronary infusion of BH4 restores coronary endothelial function by improving the bioavailability of endothelium derived nitric oxide in hypercholesterolaemic patients. P atients with various coronary risk factors, such as hypercholesterolaemia, have been shown to have impaired coronary artery endothelium dependent vasodilatation in response to acetylcholine (ACh), which is characterised by reduced endothelium derived nitric oxide bioavailability.1-5 It has been reported that tetrahydrobiopterin (BH4) serves as an essential cofactor for endothelial nitric oxide synthase 6 7 and that reduced bioavailability of BH4 during activation of nitric oxide synthase decreases nitric oxide production, while simultaneously increasing formation of oxygen derived free radicals. [8][9][10] In addition, a recent study suggested that BH4 may serve as a scavenger of oxygen derived free radicals. 11Therefore, intracellular BH4 concentrations in endothelial cells may be decreased in patients with impaired endothelial function. In support of this hypothesis, recent studies have shown that supplementation of BH4 improves impaired endothelial function under various pathological states in vivo, including hypercholesterolaemia and smoking.12 13 In addition, Maier and colleagues 14 reported that BH4 improves impaired coronary vascular responses to ACh in the coronary arteries of patients with coronary artery disease. However, most of the patients involved in these studies had multiple coron...

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Our data suggest that nitric oxide modulates basal coronary artery tone but that mediators other than nitric oxide may be responsible for the flow-mediated vasodilation of human epicardial coronary arteries.