HETEROGENEITY OF VASOMOTOR RESPONSE TO ACETYLCHOLINE ALONG THE HUMAN CORONARY-ARTERY

Objectives. In view of the segmental occurrence of coronary atheroscle rosis, we postulated that acetylcholine may cause heterogeneous vasomo tion, depending on the extent of vessel analyzed, criteria for change in vessel caliber and dose of drug administered. Background. Previous studies have reported that acetylcholine causes constriction of athero sclerotic arteries. This dysfunction of endothelium-dependent dilation may be seen without angio graphically detectable disease. Methods. We developed algorithms to quantitate the dimensions of a single coronar y artery over virtually its entire length during a control state and d uring graded doses of intracoronary acetylcholine. On the basis of tri plicate control angiograms, the limit of detection of a change from co ntrol diameter was 0.31 mm (greater than or equal to 2 SD). Results. A nalysis of multiple segments (each 5.6 +/- 1.1 [mean +/- SD] mm) along a single coronary artery revealed a heterogeneous response to acetylc holine in 27 of 31 patients at the 10(-4) mol/liter dose and in 29 of 31 patients when responses at 10(-6), 10(-5) and 10(-4) moliliter dose s were combined; in this latter analysis, constriction and dilation in the same vessel occurred in 45% of the patients. With acetylcholine, most of 349 segments demonstrated no change, but the greatest frequenc y of vasoconstriction (24.6%) and vasodilation (6.9%) was seen at the 10(-4) mol/liter dose. Inducible vasomotion was observed as far distal ly as 7.3 cm from the site of acetylcholine infusion. Conclusions. Res ponse to intracoronary acetylcholine with mild coronary disease is het erogeneous; disparate dimensional responses may occur in different seg ments of the same vessel. Inclusion of all analyzable regions of a cor onary artery and the use of a reproducibility limit for quantitative a ngiography are optimal for assessment of segmental coronary vasomotion .