Mechanisms of estrogen-induced vasodilation: in vivo studies in canine coronary conductance and resistance arteries.

OBJECTIVES: We sought to examine the immediate vasodilator effect of intracoronary estrogen on epicardial and resistance coronary arteries in 19 dogs. BACKGROUND: Although estrogen reportedly dilates coronary arteries in vitro, the site and mechanisms of its action have not been fully defined in vivo. METHODS: Epicardial coronary artery dimensions and coronary flow velocity were assessed using simultaneous intracoronary two-dimensional and Doppler ultrasound. RESULTS: Estrogen (0.1 and 1 mumol/liter) induced a significant increase in coronary cross-sectional area, flow velocity and volumetric blood flow. Estrogen-induced vasodilation was not influenced either by pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME) (100 mumol/liter intracoronary), indomethacin (5 mg/kg body weight intravenously), propranolol (0.75 mg/kg intravenously) or the classic estrogen receptor antagonist ICI 182,780 (10 mumol/liter). Balloon denudation of the endothelium did not attenuate estrogen-induced epicardial vasodilation. Pretreatment with glibenclamide (10 mumol/liter) attenuated estrogen-induced vasodilation only in epicardial arteries, as did verapamil (0.1 mumol/liter). Estrogen had no effect on a phenylephrine dose-response curve in either epicardial coronary arteries or the microcirculation. CONCLUSIONS: Acute estrogen-induced dilation in canine coronary arteries is endothelium independent and is not mediated by the classic intracellular estrogen receptor but through non-genomic mechanisms, presumably at the membrane level, which in epicardial arteries may include effects on adenosine triphosphate-sensitive potassium or calcium channels, or both.

Contrast-enhanced intravascular ultrasound: validation of a new technique for delineation of the vessel wall boundary.

OBJECTIVES: We evaluated a new technique for delineation of the vessel wall surface during intravascular ultrasound imaging using echogenic contrast agents. BACKGROUND: Intravascular ultrasound is used for detection of complex vessel wall structures after catheter-based interventions; however, differentiation between the lumen and these wall structures can be difficult. METHODS: In 12 anesthetized dogs, intracoronary ultrasound was performed during intracoronary bolus injection (3 and 6 ml) of different contrast agents (hand-agitated saline solution, standard iohexol, sonicated iohexol, hand-agitated iohexol, SHU 454, SHU 508). Contrast intensity was quantified by videodensitometry, and contrast homogeneity was assessed qualitatively (grade 0 to 3). RESULTS: Peak contrast intensities for SHU 454 and SHU 508 (mean [+/- SD] 48 +/- 9 and 36 +/- 6 U, respectively) were higher compared with standard, sonicated or agitated iohexol (16 +/- 3, 28 +/- 7 and 20 +/- 3 U, respectively) or with agitated saline solution (17 +/- 4 U); intensities were higher for 6 ml compared with that for 3 ml. Contrast homogeneity was higher for SHU 508 (mean [+/- SD] 3.0 +/- 0) and SHU 454 (2.7 +/- 0.5) compared with the other agents (standard iohexol 1.2 +/- 0.4, sonicated iohexol 2.0 +/- 0.5, agitated iohexol 1.8 +/- 0.6, agitated saline solution 1.0 +/- 0.4). Exact delineation of the vessel wall surface was possible in 100% of SHU 508 and in 88% of SHU 454 injections compared with 13% of agitated iohexol and 8% of sonicated iohexol injections. Accurate surface delineation was never achieved with standard iohexol or agitated saline solution. Shadowing of parts of the vessel wall by contrast material occurred at peak intensity of 75% of SHU 508 and 46% of SHU 454 injections but not with the other agents. No adverse physiologic reactions were noted, except for transient negative inotropic effects after 6 ml of SHU 508. CONCLUSIONS: This preliminary study shows that delineation of the vessel wall boundary using echogenic contrast agents during intravascular ultrasound is safe and feasible. Because of higher contrast intensity and homogeneity, SHU 454 and SHU 508 are superior to other agents.

Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: correlation with high density lipoproteins.

OBJECTIVES: This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultrasound imaging. BACKGROUND: Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis. METHODS: Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque. RESULTS: Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [+/- SD] 0.25 +/- 0.16) than in the left main (0.11 +/- 0.16, p < 0.001) and iliac arteries (0.02 +/- 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index > or = 0.42 (left anterior descending artery) and > or = 0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery. CONCLUSIONS: In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease.

Acute myocardial infarction and vascular remodeling.

We used intravascular ultrasound to show that outward remodeling predominates in lesions responsible for acute myocardial infarction, whereas negative remodeling is far more prevalent in lesions responsible for chronic stable angina. The total cholesterol:high-density lipoprotein ratio was also strongly correlated with outward remodeling.

Contribution of endothelium-derived nitric oxide to coronary arterial distensibility: an in vivo two-dimensional intravascular ultrasound study.

Reduced epicardial coronary arterial distensibility associated with early atherosclerosis may be mediated in part by reduced nitric oxide (NO) release. To directly assess the contribution of endogenous NO to coronary arterial distensibility, we examined the effect of intracoronary N omega nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, and L-arginine, its natural substrate, on the circumflex artery in seven anesthetized dogs. We also used intracoronary acetylcholine to examine the effect of pharmacologically induced NO release on coronary distensibility. Electrocardiographically gated measurements of epicardial coronary lumen area were made by a blinded observer from images obtained with a 4.3F, 30 MHz intravascular ultrasound catheter. Aortic root pressure was continuously monitored, and neither systemic arterial pressure nor pulse pressure changed significantly with intracoronary drug administration. Change in lumen area (delta LA) from end systole to end diastole was measured, and an arterial distensibility index was calculated. Delta LA increased with acetylcholine from 8.2% +/- 0.5% at baseline to 16.3% +/- 2.8% (10(-6) mol/L; p < 0.001), with increases in both end-systolic and end-diastolic lumen area and decreased delta LA to 3.1% +/- 1.3% (p < 0.01). Lumen area and delta LA were both restored to baseline by L-arginine (10(-4)). The calculated distensibility index of the epicardial coronary artery was enhanced by acetylcholine, reduced below baseline by L-NAME, and restored to baseline by L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracoronary ultrasound imaging: intraobserver and interobserver variability of morphometric measurements.

Measurements of lumen and plaque dimensions by intracoronary ultrasound imaging are useful in assessing effects of intracoronary interventions and in quantifying plaque burden in transplant patients or during regression trials. However, these measurements are affected by inter- and intraobserver variability. In 87 patients, 120 intracoronary ultrasound images were obtained with a 4.3F, 30 MHz catheter. Morphometric measurements were performed two times by three independent observers using computerized planimetry. Intraobserver and interobserver agreement for qualitative parameters (presence of atherosclerotic plaque, calcified plaque, and residual nondiseased wall) was high (> 87%). For quantitative parameters measured directly in the images (lumen area, minimal and maximal lumen diameters, area within the internal elastic lamina, arc of calcium plaque) interobserver and intraobserver correlation between measurements was high (correlation coefficient r > 0.90) and differences between measurements were low (mean differences < 10%; SD < 20%). Measurement of the arc of nondiseased wall showed less interobserver correlation (r = 0.76 to 0.91), but percentages of difference between the measurements were low. Parameters derived from directly measured variables (plaque area, area stenosis, thickness, and eccentricity) showed slightly higher variability (correlations between measurements r = 0.78 to 0.91). SD for percentages of difference ranged between 20% and 30% (plaque area, area stenosis, and thickness) and systematic deviation between measurements (mean differences > 10%) occurred for plaque area. Thus most qualitative and quantitative measurements of lumen and plaque dimensions performed in intracoronary ultrasound images have low in intraobserver and interobserver variability; derived parameters may have slightly higher variability. Variability of morphometric measurements has to be considered, especially when serial ultrasound measurements are compared.