Effect of cutaneous nitroglycerin patches on coronary artery diameter: Issues concerning development of tolerance

Abstract

The coronary dilative and systemic responses to graded doses of intracoronary nitroglycerin were studied in 53 patients undergoing diagnostic coronary arteriography, 43 of whom had received a cutaneous nitroglycerin patch. During coronary arteriography, graded doses of 50, 100 and 200 μg of intracoronary nitroglycerin were given 5 min apart. An arteriogram and hemodynamic measurements were obtained after each dose. In the control group (n = 10) cumulative intracoronary nitroglycerin doses of 50,150 and 350 μg caused an increase in coronary diameter in the left anterior descending artery of 20 ± 4%, 21 ± 3% and 22 ± 7%, respectively, and in the circumflex artery of 18 ± 6%, 23 ± 8% and 18 ± 5% (p < 0.01 versus values in untreated group).In Group 1 (15 patients given a 5 mg/24 h nitroglycerin patch 2 to 12 h before coronary arteriography), the same intracoronary nitroglycerin doses increased the left anterior descending artery diameter by 6 ± 2%, 7 ± 2% and 7 ± 2%, respectively, and the circumflex artery diameter by 3 ± 2%, 3 ± 2% and 1 ± 3%. All values were statistically different from control (p < 0.05). An even more pronounced blunting (p < 0.01) of the coronary dilative response was observed in Group 2 (14 patients given a 15 mg/24 h nitroglycerin patch 2 to 12 h before arteriography). The diameter responses to intracoronary nitroglycerin observed in Group 3 (seven patients given a 5 mg/24 h nitroglycerin patch 24 h before arteriography) and Group 4 (seven patients given a 15 mg/24 h nitroglycerin patch 24 h before arteriography) were not significantly different from those of the control group.The results demonstrate that a nitroglycerin patch administered a few hours before coronary arteriography caused significant coronary artery dilation and that the incremental dilation due to the intracoronary nitroglycerin was small. On the other hand, 24 h after arteriography, the coronary dilative effect of the patch was attenuated (suggesting development of tolerance) and the increment in diameter induced by intracoronary nitroglycerin was much larger.