Hyperplasia of coronary intima in young males in relation to development of coronary heart disease in adults

The aim of the investigation was to study structural features of coronary arteries in young males which may influence the development of stenosing coronary atherosclerosis in older age. We studied the coronary arteries from 84 males, 10-39 years old, who died from accidents in Moscow, Malmo and Riga, and 98 males aged 40 and above from Moscow who died from coronary heart disease (71 cases) or other diseases (27 cases). In children and young males from all three cities, musculo-elastic hyperplasia of the coronary intima took place constantly but with different degrees of expression; a strict relationship of the intimal thickness and age was observed. Histometric investigations of the right coronary artery showed that in young males of Riga, in comparison with those of Malmo, the intima was significantly thicker both outside (69.6+/-2.8 and 58. 2+/-2.5 microm) and within the area of cushion like thickening (118. 8+/-4.0 and 101.9+/-3.8 microm), they had more extended cushion-like thickening of intima (42.6+/-3.0 and 30.8+/-3.3% to the length of the artery circumference) and destroyed parts of the internal elastic lamina (28.3+/-1.9 and 19.1+/-1.7% of its length). In males older than 40 years, severe coronary atherosclerosis and stenosis was also significantly more common in Riga than in Malmo. Our data indicate that with age the intimal musculo-elastic hyperplasia in the coronary arteries is transformed to a fibro-elastic layer. The thickness of this layer in the presence of stenosing plaques (>75% of arterial lumen) was much greater than in the presence of plaques with stenoses less than 50% (188.1+/- 7.3 and 69.8+/-4.5 microm, respectively). CONCLUSION: The development of stenosing coronary atherosclerosis is closely related to the degree of musculo-elastic intimal hyperplasia in childhood and young age. The formation of a fibro-elastic layer in the coronary intima decreases the ability of the artery to dilate during the development of atherosclerosis.     

The intima of human coronary arteries

Intimal thickness relative to that of the media (r) was measured in coronary and internal mammary arteries from 300 human subjects. Whereas this ratio remained low (less than 0.17) in the mammary arteries, coronary arteries showed progressive intimal thickening (r = 4.10 by 60 years). The intimal surfaces of 70 pairs of arteries were compared by light, transmission, and scanning electron microscopy. The mammary arteries had a continuous endothelial lining, but the coronary arteries showed incomplete coverage of the thickened intima. In affected vessels the endothelial cells showed loss of attachment to adjacent cells and to the underlying tissue. It was concluded that the progressive intimal thickening of the human coronary artery, which develops early in life and is associated with defects in the internal elastic lamina, is also associated with endothelial cell separation and detachment, with the formation of denuded areas on the intimal surface.     

Diffuse intimal thickening of coronary arteries in slow coronary flow

Intravascular ultrasound imaging can detect intimal thickening and is suitable for detection of early atherosclerosis, which cannot be detected by conventional angiography. The aim of the present study was to investigate the epicardial coronary morphology and intracoronary pressure in relation to slow coronary flow (SCF). The study population consisted of 19 patients with SCF [11 (57.9%) females; 55.95 +/- 9.42 years]. Proximal, middle, distal and mean total vessel area, lumen area, intima + media area (IMA), percent IMA, and maximal intima + media (I + M) thickness were calculated and compared to healthy subjects. Proximal, middle, distal and mean I + M thickness, IMA, and % IMA of patients with SCF were found to be significantly higher than those of control subjects. Longitudinally extended massive calcification throughout the epicardial arteries was found in 13 (68.49%) patients with SCF and regional calcification was found in 6 (31.6%) patients with SCF. Proximal and distal pressure gradients of patients with SCF were determined to be 15.84 +/- 12.11 mmHg in the intracoronary pressure measurements. Fractional flow reserve values were significantly lower than the normal population (0.83 +/- 0.13, P < 0.0001). This study indicates that patients with SCF have diffuse intimal thickening, widespread calcification along the vessel wall and atheroma which does not cause luminal irregularities in coronary angiography, and a pressure gradient between proximal and distal segments of epicardial coronary arteries with SCF. Based on these results, we believe that SCF may be a form of diffuse atherosclerosis involving both the microvascular system and epicardial coronary arteries.     

Infection-associated intimal thickening in the coronary arteries of children

OBJECTIVES: based on autopsy material from children this study investigated the possible relationship of clinically evident infection prior to death with intimal thickening of the coronary arteries. BACKGROUND: viral infections are suggested to be associated with intimal thickening in the coronary arteries both in animals and man. METHODS: the coronary arteries were examined in 175 autopsied children 0-15 years of age (median 7 days). Semi-serial cross sections of the coronary arteries were screened for maximal intimal thickening at 0.2 mm intervals. The length of the internal elastic lamina, the areas of arterial media and intima were measured from cross-sections. Irregular linings of the arteries were mathematically transformed to circles. The percentage of intimal and musculoelastic layer area to luminal area encircled by arterial media was calculated. RESULTS: intimal thickening increased with age but was also associated with the presence of infectious disease at death. Already in the newborn children, who died shortly after the birth, the percentage of intimal and musculoelastic layer area to luminal area encircled by arterial media was big, maximally 55%. In the left coronary artery the mean percentages were 32 and 21% in the groups with viral and bacterial infections, respectively as compared to 16% in the group with no evidence of infection. CONCLUSION: infections in general and viral infections in particular, seem to be associated with intimal thickening, which may predispose coronary arteries to atherosclerosis. Atherogenesis might have a rapid dynamic component.     

A comparison of coronary and internal mammary arteries and implications of the results in the etiology of arteriosclerosis

Comparison was made between the intimal thickening of the anterior descending branch of the left coronary artery and the internal mammary artery in 352 necropsy examinations. The coronary arteries showed severe intimal thickening, progressing in severity throughout life, whereas the internal mammary showed no more than slight changes at any age. These observations, together with the variation in severity of the changes in different portions of the same vessel, and the freedom from this disease of the smaller arteries throughout the body, strongly suggest that a local or anatomic factor is the dominant influence in coronary artery disease.     

Changes of coronary artery morphology and distribution of smooth muscle cells during progression of coronary atherosclerosis after heart transplantation

To examine the changes in coronary artery morphology and the distribution of smooth muscle cells during the progression of coronary atherosclerosis after cardiac transplantation, intimal and medial tissues were evaluated and the density of smooth muscle cells in the media were measured 30 and 60 days after transplantation by microspectrophotometry from rats receiving both auto- and allo-transplantation. Transplanted animals were given cyclosporine A to prevent graft rejection. Signs of rejection were not seen in the animals receiving auto-transplants. Rejection gradually progressed after transplantation in animals receiving allografts. The intima of the coronary arteries in the allograft group was significantly thickened at both 30 and 60 days after transplantation. The total intimal area in the day 60 group was significantly increased relative to the day 30 group among animals receiving allo-transplantation. The medial area of the coronary arteries in the group receiving allotransplantation was significantly less than that of the auto-transplantation group at both 30 and 60 days after transplantation. Azocarmine G stain revealed that the principal component of the thickened intima was smooth muscle cells. Coronary arteries in the allotransplantation group had disruption of the internal elastic lamina. We therefore hypothesized that the smooth muscle cells (SMCs) in the intima are probably derived from the media. The density of SMCs in the media was measured by microspectrophotometry. The density of SMCs was significantly decreased in the allo-transplantation group relative to the autotransplantation group. We conclude that intimal thickening of the coronary arteries is due to SMC proliferation, the myocytes being from the media through disruption of the internal elastic lamina. This process is similar to the mechanism of the development of atherosclerosis.     

Discontinuities in the internal elastic lamina: a comparison of coronary and internal mammary arteries

The internal elastic lamina (iel.) of the anterior descending branch of the left coronary artery, and the internal mammary artery, were studied in 166 unselected subjects of different ages and races. The coronary artery showed substantial defects in the iel. even in the first few years of life, while the iel. of the mammary artery showed only minimal defects in all age groups. The defects in the iel. were associated with the presence of medial cells in the intima, and the thickness of the intima was correlated with the magnitude of the defects in the iel. (Correlation coefficient 0.95 for the coronary artery and 0.80 for the mammary artery). Small arteries involved in chronic inflammatory or neoplastic disease showed a similar relationship if the vessel were present in an edematous area. These vessels which do not usually show intimal thickening, displayed a thickened intima in the vicinity of defects of the iel. It is suggested that the pronounced difference in the incidence of arteriosclerosis between the coronary and internal mammary arteries is related to these defects in the internal elastic lamina.     

Left anterior descending coronary artery wall thickness measured by high-frequency transthoracic and epicardial echocardiography includes adventitia

High-frequency, 2-dimensional transthoracic echocardiography (HR-2DTTE) measurements of the left anterior descending (LAD) coronary artery wall thickness are larger than measurements obtained by intravascular ultrasound. We hypothesize that this difference is due to inclusion of the third vascular layer, which may represent adventitia by HR-2DTTE, and that this layer must be increasing in thickness with the development of atherosclerosis. We evaluated the contribution of this third layer to the wall thickness of the normal and atherosclerotic LAD artery imaged by HR-2DTTE using high-frequency epicardial echocardiography (HFEE) as the reference standard. Eighteen patients (10 men, mean age 62 years), 13 with coronary atherosclerosis and 5 with normal coronary arteries, referred for open-heart surgery, underwent preoperative HR-2DTTE evaluation of the LAD artery (SONOS 5500; 3- to 8-MHz transducer) and intraoperative HFEE of the LAD artery (SONOS 5500; 6- to 15-MHz transducer). Wall thickness was greater in patients with coronary atherosclerosis than in those with normal coronary arteries by both HR-2DTTE (1.9 +/- 0.3 vs 1.0 +/- 0.1 mm, p = <0.001) and HFEE (1.8 +/- 0.2 vs 1.0 +/- 0.2 mm, p = <0.001). On HFEE, the average intima plus media thickness was greater in patients with coronary atherosclerosis than in those with normal coronary arteries (0.78 +/- 0.3 vs 0.34 +/- 0.1 mm, p = 0.005). The average thickness of adventitia was also greater in patients with coronary atherosclerosis than in those with normal coronary arteries (0.92 +/- 0.2 vs 0.54 +/- 0.2 mm, p = 0.0005). HR-2DTTE and HFEE measurements of the wall thickness correlated well (r = 0.83 [reader 1], p <0.001; r = 0.61 [reader 2], p <0.01). A third vascular layer, which likely included adventitia, represents a significant portion of the LAD wall thickness imaged by HR-2DTTE and HFEE, and it significantly increases in thickness with the development of atherosclerosis.     

Detection of coronary atherosclerosis in young adult hearts using intravascular ultrasound.

BACKGROUND. Coronary atherosclerosis has been demonstrated in young adults by postmortem pathology. Angiographic evaluation of coronary disease in young adults is limited by ethical issues and the insensitivity of angiography for detecting early pathology. Catheter-based intracoronary ultrasound has proven useful both in detecting and quantitating coronary disease, but the ultrasound appearance of young, angiographically normal, coronary arteries has not been well defined. METHODS AND RESULTS. Twenty-five subjects were examined with intracoronary ultrasound within 1 month of cardiac transplantation. Mean age of the donor hearts was 28 years (range, 14-43 years). Measurements of an index of intimal thickening were obtained at four left anterior descending coronary artery sites in each patient. All study patients had angiographically normal coronary arteries. Ultrasound in 14 subjects demonstrated a three-layered appearance of the coronary vessel wall with a mean intimal index of 0.16 +/- 0.07. The other 10 subjects, including all donors under the age of 25 years, had coronary vessel wall layers too thin to be imaged separately at the 30-MHz sound frequency. Five subjects had ultrasound evidence of focal intimal thickening greater than 500 microns. The donors of these hearts each had risk factors for coronary artery disease. Two subjects died within 5 weeks of their ultrasound study. Histological measurements of the vessel wall layers were similar to the corresponding ultrasound values. CONCLUSIONS. This study provides a reference for the intravascular ultrasound appearance of young adult coronary arteries and confirms pathology findings that young subjects with angiographically normal vessels have a range of coronary intimal thickening, which includes occasional evidence of focal, early atheromatous lesions.     

Distribution of intimal and medial thickening in the human right coronary artery: a study of 17 RCAs

OBJECTIVE: To quantify the distribution of intimal and medial thickening in human right coronary arteries (RCAs) obtained at autopsy. BACKGROUND: The shear and tensile stresses created by arterial bifurcation are believed to result in eccentric fibromuscular intimal thickening that leads to atherosclerosis. Vascular curvature has been cited as a cause of atherosclerosis; however, details of the location and extent of intimal and medial thickness in the largely curved human RCA are not adequately documented. METHODS: The right coronary arteries were obtained from 40 postmortem hearts and cut into 20-30 segments, each being 3-4 mm in length. Microscopic sections from the proximal, acute margin, and distal regions of the RCA were digitized around the circumference of the vessel. Seventeen arteries showed insignificant stenosis (<50%) and were selected for detailed examination. RESULTS: Seventy-one percent (12/17) of proximal sections displayed eccentric intimal thickening. Normalized ensemble averaging revealed a preferential thickening on the myocardial side of the artery. At the acute margin region where curvature is most pronounced and at the distal region, 51% (8/17) of the samples showed eccentric thickening, but the ensemble average thickening in these regions showed no preferential location. In these mildly diseased arteries, the thickened intima comprised of mainly smooth muscle cells with an extracellular matrix of collagen and some elastin. A relatively uniform medial smooth muscle layer was seen at all three locations. CONCLUSIONS: The proximal region of the RCA appears to be a site of intrinsic eccentric intimal thickening with maximum thickness on the myocardial side of the artery. Eccentric thickening does occur in the acute margin and distal regions; however, no distinct pattern or location was evident.     

Coronary artery bypass grafting by utilizing the internal mammary artery graft in 100 Japanese patients

The internal mammary artery (IMA) grafting for myocardial revascularization was performed in 100 Japanese patients during a three-year period. There were 86 males and 14 females with the mean age of 58 +/- 9 (37 approximately 75 year-old). Unilateral IMA was used in 88 patients and bilateral IMA was used in 12 patients. Sequential IMA grafting was performed in 5 patients. The sites of IMA grafting were 91 left anterior descending arteries (LAD), 16 diagonal branches, 8 circumflex arteries and 2 right coronary arteries. Saphenous vein or gastroepiploic artery was concomitantly used to bypass the other coronary arteries in 90 patients. The number of distal anastomosis ranged from 1 to 6 and the mean was 2.8 per patient. Two patients died within 30 days and one patient died at 3 months after surgery. Perioperative myocardial infarction was noted in 3 patients. Symptomatic relief was obtained in 94 (97%) of 97 survivors. The patency of the IMA graft at mean 2.2 postoperative months was 97% (58/60) in LAD, 100% (14/14) in the diagonal branch, 100% (5/5) in the circumflex artery, 100% (1/1) in the right coronary artery, and 98% (78/80) in over-all grafted coronary arteries. Pre- and postoperative exercise thallium scintigraphy in 13 patients, who received the IMA graft to severely stenosed LAD, showed significant improvement of the washout ratio (from 33.1 +/- 16.9% to 47.4 +/- 14.8%) which was nearly equivalent to that of the saphenous vein graft to LAD (from 24.8 +/- 6.2% to 48.1 +/- 6.6%, n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)     

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 ultraound 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 0.42 (left anterior descending artery) and 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.     

Paraoxonase producing PON1 gene M/L55 polymorphism is related to autopsy-verified artery-wall atherosclerosis

Paraoxonase (PON) is an antioxidative enzyme, which eliminates lipid peroxides. PON has two common polymorphisms (M/L55 and R/Q192) that influence PON concentration and activity. We studied whether the M/L55 or R/Q192 genotype relates with the severity of atherosclerosis of the abdominal aorta, and the mesenteric and common iliac arteries in 123 consecutive autopsy cases (90 males and 33 females, aged 18-93 years). The severity of atherosclerosis in the arteries was evaluated, and the percentage of stenosis was measured. The intimal thickness in the internal elastic lamina (IEL) of the coeliac (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries were measured by light-microscopy. The LL homozygous men had more atherosclerotic plaques and complicated lesions in the common iliac arteries (56.8%) than the M allele carriers (28.3%, P=0.007). In logistic regression analysis, age (P<0.001) and the PON M/L55 genotype (P=0.015) were associated significantly with the severity of atherosclerosis in the common iliac arteries independent of smoking status, R/Q192 genotype, hypertension, diabetes mellitus, BMI and sex. The mean intima of the IMA was significantly thicker (P=0.035) and the number of stenotic lesions in SMAs significantly higher (P=0.008) in the LL homozygous men than M allele carriers. In turn, the R/Q192 genotype was not statistically significantly associated with plaque type, intimal thickness in the IEL or with the number of stenotic lesions. This study demonstrates that PON L55 homozygosity is an independent risk factor for autopsy-verified atherosclerosis in Finns.     

Intracoronary ultrasound assessment late after the arterial switch operation for transposition of the great arteries

OBJECTIVES: This research was undertaken to assess the status of the coronary wall morphology late after the arterial switch operation (ASO) for transposition of the great arteries employing intravascular ultrasound (IVUS). BACKGROUND: Long-term patency of the reimplanted coronary arteries is a key issue after ASO. Follow-up studies have demonstrated coronary obstruction in up to 8% of patients that may be related to progressive fibrocellular intimal thickening. METHODS: Twenty-two asymptomatic children were enrolled at a median age of 9.5 years (range 5 to 22 years); IVUS images were obtained in 20 children at cardiac catheterization 5.0 to 21.6 years after the operation (in two cases IVUS study was not feasible due to technical constraints). Quantitative analysis was performed in 37 coronary arteries involving segments with a mean length of 28.4 +/- 1.8 mm. RESULTS: Thirty-three arteries (89%) displayed variable degrees of proximal eccentric intimal proliferation, with the maximal intimal thickening being 0.26 +/- 0.14 mm (range 0.06 to 0.71 mm) at the most thickened site. According to the Stanford classification, all children had coronary artery involvement with 50% having moderate-to-severe lesions (>0.3 mm). No risk factors for such abnormalities were encountered, including age, origin of the coronary arteries, hemodynamics, and follow-up duration after surgery. CONCLUSIONS: Intravascular ultrasound assessment late after the ASO revealed proximal eccentric intimal thickening in most of the studied vessels. This observation suggests the development of early atherosclerosis in the reimplanted coronary arteries, which may have a role in the genesis of late coronary events.     

Retrograde internal mammary to coronary artery anastomoses

In an effort to expand the utilization of the internal mammary artery (IMA) for revascularization of the distal coronary artery branches, distally pedicled retrograde internal mammary arteries (retro-IMA) were evaluated in 10 mongrel dogs with a mean weight of 38 +/- 13 kg. One IMA was transected at it's origin (retro-IMA) and compared to the contralateral IMA which was transected at the level of the 5th intercostal space. At a mean systemic pressure of 68 +/- 15 mmHg the mean pressure measured at the tip of the IMAs with antegrade flow was 63 +/- 14 mmHg in the retro-IMAs with retrograde flow (p less than 0.05; pressure ratio 0.8). With the same mean systemic pressure, mean antegrade free flow of the IMAs was assessed 97 +/- 43 ml/min versus 48 +/- 13 ml/min in the retro-IMAs with retrograde flow (p less than 0.005; flow ratio 0.5). Left retro-IMA to coronary artery anastomosis was performed in 6 animals to the distal left anterior descending (LAD) coronary artery and in 2 animals to the distal left obtuse marginal branch. Right retro-IMA to coronary artery anastomosis to the right posterior descending coronary artery was performed in 2 animals. The LAD coronary artery was ligated proximally to the retro-IMA to coronary artery anastomosis while the retro-IMA remained crossclamped. After documentation of significant ischemia (EKG, left atrial pressure), the crossclamp of the retro-IMA graft was removed. Subsequent normalisation of EKG and left atrial pressure occurred in all animals. We conclude that the canine retro-IMA delivers significant retrograde flow and discuss a possible use in humans.     

Ubiquitous atherosclerosis in coronary arteries without angiographically significant stenosis

Previous intravascular ultrasound (IVUS) studies have shown coronary artery atherosclerosis even in angiographically normal reference segment. However, IVUS has not been performed in all of the three major coronary arteries. A total of 50 patients with single-vessel disease underwent IVUS evaluation in the proximal two-thirds of the three major coronary arteries. Lumen and external elastic membrane cross-sectional areas were measured at 1-mm intervals. To compensate the difference in pullback length among coronary arteries, normalized total plaque and media volume (TPV) was calculated as TPV/number of slices in pullback × median number of slices in study population. Percent plaque and media volume (PPV) was calculated as TPV/Σ external elastic membrane cross-sectional area × 100. A cross section was defined as atherosclerotic if maximum intimal thickness exceeded 0.5 mm at any point in the vessel circumference. There was no significant difference in normalized TPV, PPV, and the incidence of abnormal intimal thickness between coronary arteries with and without significant stenosis. Frequency distribution of plaque burden was similar. Atherosclerosis is ubiquitous even in coronary arteries without angiographically significant stenosis. The extent of atherosclerosis is similar between coronary arteries with and without significant stenosis.     

Potential use of high-resolution two-dimensional transthoracic echocardiography for visualization of the left anterior descending coronary artery

High-resolution, two-dimensional transthoracic echocardiography (HR-2DTTE) can detect the difference in the left anterior descending coronary artery (LAD) wall thickness between patients with coronary artery disease and patients with normal coronary arteries. However, HR-2DTTE measurements of the LAD wall thickness are larger than measurements obtained by intravascular ultrasound and histology. This difference may be due to the inclusion of adventitia by HR-2DTTE. We evaluated the contribution of adventitia to the wall thickness of the normal and atherosclerotic LAD by comparing HR-2DTTE with high-frequency epicardial echocardiography. The LAD wall thickness was significantly greater in patients with coronary artery disease by both HR-2DTTE and high-frequency epicardial echocardiography. Both an increase in the intima plus media thickness and an increase in the thickness of adventitia contributed to the increase in the LAD wall thickness in patients with coronary artery disease. Adventitia represents a significant portion of the LAD wall thickness imaged by HR-2DTTE and its thickness increases significantly with the development of atherosclerosis.     

Intracoronary ultrasound in cardiac transplant recipients. In vivo evidence of "angiographically silent" intimal thickening.

BACKGROUND. Accelerated coronary atherosclerosis is a major factor limiting allograft longevity in cardiac transplant recipients. Histopathology studies have demonstrated the insensitivity of coronary angiography for detecting early atheromatous disease in this patient population. Intracoronary ultrasound is a new imaging technique that provides characterization of vessel wall morphology. The purpose of this study was to compare in vivo intracoronary ultrasound with angiography in cardiac transplant recipients. METHODS AND RESULTS. The left anterior descending coronary artery was studied with intracoronary ultrasound in 80 cardiac transplant recipients at the time of routine screening coronary angiography 2 weeks to 13 years after transplantation. A mean and index of intimal thickening were obtained at four coronary sites. Intimal proliferation was classified as minimal, mild, moderate, or severe according to thickness and degree of vessel circumference involved. Twenty patients were studied within 1 month of transplantation and had no angiographic evidence of coronary disease. An intimal layer was visualized by ultrasound in only 13 of these 20 presumably normal hearts. The 60 patients studied 1 year or more after transplantation all had at least minimal intimal thickening. Twenty-one patients (35%) showed minimal or mild, 17 (28%) moderate, and 21 (35%) severe thickening. Forty-two of these 60 patients had angiographically normal coronary arteries, 21 (50%) of whom had either moderate or severe thickening. All 18 patients with angiographic evidence of coronary disease had moderate or severe intimal thickening, but there was no statistically significant difference in intimal thickness or index when compared with the patients with moderate or severe proliferation and normal angiograms (thickness, 0.53 +/- 0.35 mm versus 0.64 +/- 0.30 mm, p = NS; index, 0.28 +/- 0.10 versus 0.34 +/- 0.10, p = NS). CONCLUSIONS. The majority of patients 1 or more years after cardiac transplantation have ultrasound evidence of intimal thickening not apparent by angiography. Intracoronary ultrasound offers early detection and quantitation of transplant coronary disease and provides characterization of vessel wall morphology, which may prove to be a prognostic marker of disease.     

Internal mammary arteriography: a new catheter technique by right brachial approach

A technique for catheterization of both internal mammary arteries (IMAs) by right brachial approach is described. A special preformed catheter was used in 75 patients with coronary artery disease, including ten patients with direct IMA grafts. No complications occurred. The IMAs were studied to examine the question of their usefulness in direct myocardial revascularization. There were individual variations in the size of IMAS with poor correlation to age (r = -0.432)) and body surface area (r = 0.517). Seventy percent of the women had adequate IMAs. The IMA diameter was equal to or larger than the left anterior descending coronary artery (LAD) in 72% and the right coronary artery (RCA) in 34% of comparisons. Of the ten patients with direct IMA grafts, three instances of large side branches were seen. These branches appeared to carry large flows at the expense of the grafted coronary artery. Preoperative internal mammary arteriography should be done if the use of this vessel is contemplated in direct myocardial revascularization to assure the use of an IMA of adequate caliber compared to the recipient coronary artery. The side branches should be meticulously ligated during the operation.     

Detection of early atherosclerosis in M. fascicularis with transcutaneous ultrasonic measurement of the elastic properties of the common carotid artery

The elastic properties of 22 common carotid arteries from 13 male cynomolgus monkeys (M. fascicularis) that were fed either a high cholesterol (test) diet or a standard monkey chow (control) diet for 18 months were measured noninvasively with 5 MHz ultrasound. A B-mode image of the artery was obtained with a 32-element linear array transducer, and a single line of video ultrasonic information was selected for tracking the echoes from the adventitial side of the near wall to the lumen-intima interface of the far wall. This technique measured lumen diameter plus anterior wall thickness. The diastolic diameter (Dd) (mean +/- SEM) of the test arteries was slightly larger than controls (2.9 +/- 0.1 vs 2.5 +/- 0.1 mm), whereas the fractional diameter change from diastole to systole (DeltaD/Dd, where DeltaD = diameter change) was slightly less (0.062 +/- 0.010 vs 0.082 +/- 0.011). Direct subclavian artery pulse pressure (DeltaP) in the test animals (63 +/- 4 mm Hg) was significantly greater than in the controls (41 +/- 2 mm Hg), whereas there was no difference in diastolic pressure (85 +/- 3 vs 81 +/- 2), respectively. The pressure-strain elastic modulus Ep = (DeltaP/DeltaD) Dd was significantly greater in the test monkeys (182 +/- 33 kPa) than in the controls (73 +/- 9 kPa). Morphometric analysis of atherosclerosis revealed more connective tissue and intra- and extracellular lipids in the test arteries than in the controls. Based on the average of three cross-sections equally spaced along each common carotid artery, the intimal area and the maximal intimal thickness averaged 0.89 +/- 0.16 mm2 and 0.26 +/- 0.04 mm for the test monkeys compared to negligible intimae from the controls. Medial area also was significantly greater in the test monkeys (0.71 +/- 0.03 mm2) compared to controls (0.57 +/- 0.04 mm2). Percentage stenosis defined as intimal area/IEL area, where IEL area is that within the internal elastic lamina, showed the test arteries to have 30 +/- 5% stenosis compared to 0% for the controls. However, dilatation appeared to compensate for any loss in lumen area due to intimal thickening. In this study, significant carotid artery stiffening associated with diet-induced atherosclerosis is demonstrated. This noninvasive technique may be useful in pediatrics and in preventive medicine for the detection of arterial stiffening associated with early progressive atherosclerotic lesions.