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Abstract
We sought to determine whether nitroglycerin (NTG) withdrawal contributes to worsening
of endothelial dysfunction and development of the rebound phenomenon during intermittent
transdermal NTG therapy.
Intermittent transdermal NTG therapy is recommended to avoid the development of tolerance.
However, this regimen may precipitate worsening angina in the NTG-free interval.
Twenty patients were randomized to intermittent transdermal NTG (0.6 mg/h; NTG group)
or no treatment (control group) five days before angiography. The risk factors for
endothelial dysfunction were similar in both groups. After diagnostic angiography,
the patients underwent quantitative angiography before and after intracoronary acetylcholine
(ACh), 10(-4) mol/liter. Immediately after the morning study, the patch was removed
from the NTG group, and 3 h later, the ACh infusion was repeated in both groups. All
patients had mild to moderate coronary artery disease (CAD).
The diameter of the left anterior descending coronary artery at baseline was 2.0 +/-
0.1 mm in the control group and 2.6 +/- 0.1 mm in the NTG group (p < 0.05). Acetylcholine
caused mild vasoconstriction in the control group in the morning and afternoon (2.7
+/- 5.3% and 2.4 +/- 3.9%, respectively; p = NS). The NTG group demonstrated mild
vasoconstriction to ACh in the morning (3.2 +/- 2.8%; p = NS vs. control group). After
patch removal, there was a significant increase in the magnitude ofvasoconstriction
in the NTG group (11.6 +/- 3.9%, p = 0.04 vs. morning constriction).
These results confirm that NTG withdrawal increases the coronary vasomotor response
to ACh in patients with mild CAD and suggests that the rebound phenomena may be secondary
to the development of endothelial dysfunction after discontinuation of NTG therapy.