Abstract 6098: Ascorbic Acid Restores Coronary Microvascular Function During Nitrate Withdrawal.
Background: Glyceryl trinitrate (GTN) plays a central role in the treatment of ischemic heart disease. However, tolerance and withdrawal have been associated with GTN use. Recent studies suggest that nitrates attenuate coronary endothelial function due to increased oxidative stress. It is uncertain whether oral ascorbic acid, an antioxidant, prevents this impairment during GTN withdrawal.
Methods: We enrolled 26 subjects (mean age, 61+/−9 y) with normal coronary arteries confirmed by angiography and without any medications. Before GTN administration, coronary flow velocity reserve (CFVR) in the left anterior descending artery was measured at 3:00 PM by transthoracic Doppler echocardiography during an intravenous infusion of adenosine triphosphate (0.14 mg/kg/min). The ratio of hyperemic to basal averaged diastolic peak velocity (ADPV) was defined as CFVR. All subjects received a 5-mg GTN patch, applied each evening and replaced every 24 h. Subjects were divided into 2 groups: those treated with ascorbic acid (A group, n=12, mean age 62+/−8 y) and those without ascorbic acid (N group, n=14, mean age 61+/−9 y). After 7 days, the patch was removed at 12:00 AM, and the CFVR measurement was repeated at 3:00 PM.
Results: There were no significant differences in blood pressure, HR or rate-pressure product between pretreatment and GTN withdrawal in either group. In the N group, ADPV during GTN withdrawal did not differ from baseline (21+/−6 cm/sec vs. 19+/−5 cm/sec, respectively), but hyperemic ADPV in the withdrawal state (52+/−13 cm/sec) decreased compared with baseline (61+/−15 cm/sec; P<0.05). Consequently, CFVR in the withdrawal state (2.6+/−0.6) was decreased compared with baseline (3.4+/−0.8; P<0.01). In contrast, in the A group, ADPV and hyperemic ADPV during GTN withdrawal did not differ from baseline (17+/−2 cm/sec vs. 16+/−2 cm/sec, 53+/−21 cm/sec vs. 49+/−5 cm/sec, respectively). Consequently, CFVR in the withdrawal state did not differ from baseline (3.3+/−0.6 vs. 3.1+/−0.6).
Conclusion: GTN withdrawal attenuates CFVR, but oral ascorbic acid is potentially useful for preventing this attenuation. Thus, oral ascorbic acid may restore coronary microcirculatory function and impaired CFVR by reducing oxidative stress during GTN withdrawal.