Simultaneous intracoronary ultrasound and Doppler flow studies distinguish flow-mediated from receptor-mediated endothelial responses

Abstract

Abnormalities in vascular endothelial function, which occur early in atherosclerosis, may play an etiologic role in the development of the disease or represent a marker for the extent of atherosclerosis. Endothelial dysfunction, usually characterized by demonstration of decreased endothelium‐dependent vasorelaxation, may be a sensitive and specific method to detect vascular disease in its earliest stages. In this context, separation of abnormalities in receptor‐mediated and flow‐mediated endothelium‐dependent vasodilatory responses may allow for the most accurate characterization of endothelial dysfunction. In 35 patients undergoing routine annual cardiac catheterization after heart transplantation, changes in epicardial lumen area and coronary blood flow in response to intracoronary administration of adenosine, acetylcholine, and nitroglycerin were measured simultaneously using an intravascular ultrasound (IVUS) catheter positioned over a Doppler flow wire in the left anterior descending coronary artery. The combination of these techniques allowed for distinction between receptor‐mediated and flow‐mediated endothelium‐dependent vascular responses. Peak flow with the endothelium‐independent resistance vessel dilator adenosine occurred at 18 ± 2 sec; the maximal lumen area response occurred later, at 43 ± 11 sec (P < 0.001). Acetylcholine, an endothelium‐dependent small‐ and large‐vessel vasodilator, caused an immediate increase in both flow and lumen area, but a second peak of dilation was observed, and maximal area occurred 46 sec after maximal flow (54 ± 14 vs. 100 ± 26 sec, P < 0.001). Simultaneous IVUS and Doppler flow measurements after infusion of vasoactive agents allows for distinction between and evaluation of the relative contribution of agonist‐mediated and flow‐mediated responses, which may offer important and unique insights into coronary endothelial function. Cathet. Cardiovasc. Intervent. 46:282–288, 1999. © 1999 Wiley‐Liss, Inc.

Coronary Endothelial Dysfunction After Heart Transplantation Predicts Allograft Vasculopathy and Cardiac Death

“…With this methodology, this technique has been shown to distinguish between epicardial and microvascular responses 7 and between agonist-mediated and flowmediated endothelium-dependent responses. 8 In longitudinal studies, we have shown that endothelial dysfunction predicts future progression of coronary intimal thickening in heart transplant patients, with microvascular responses to acetylcholine being stronger predictors than large-vessel responses. The present study reports the relationship between coronary endothelial dysfunction and the clinical end points of angiographically significant coronary allograft vasculopathy, ischemic events, and death in heart transplant recipients.…”

“…Continuous measurement of both parameters allowed for calculation of the maximal response, and we have shown that maximal area and flow responses do not occur at the same time. 8 In addition, epicardial responses were measured at only one point in the proximal portion of the coronary tree. Although CAV is a diffuse process, there is good evidence for segmental heterogeneity in endotheliumdependent responses in different coronary arteries and at different sites in the same coronary artery.…”

Noninvasive assessment of coronary vasodilation using magnetic resonance angiography

“…Correlations between the degree of vasodilator responses to NTG and the baseline cross-sectional area and age were also seen in our study (Fig. 6), which has been noted in previous studies (10,32,33). Interestingly, even in the healthy subjects, those with lower vasodilation (Ͻ20% area change, n ϭ 7) had a higher mean age (38 Ϯ 2 years) compared to those with Ͼ20% area vasodilation (mean age 30 Ϯ 3 years, n ϭ 12).…”

“…Impaired coronary vasodilation to nitroglycerin (NTG), an endotheliumindependent vasodilator, has also been found in patients who have coronary risk factors (9) and has also been associated with an increased risk of future cardiac events (7). However, previous studies have required either invasive X-ray coronary angiography (XRA) (1,4 -8) or intravascular ultrasound (10) to measure epicardial coronary vasodilator responses. A noninvasive technique for measuring human epicardial coronary vasodilation directly would allow more widespread study of coronary vasoreactivity in patients with, or at risk for, coronary artery disease (CAD).…”

The Endothelium – the Cardiovascular Health Barometer

“…Intravascular ultrasound analysis has been used successfully in combination with intracoronary Doppler to differentiate between flow-mediated and receptor-mediated endothelial function [38]. Still, these analyses can only evaluate the response of a small area of the epicardial artery.…”