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.     

Reduced aortic distensibility and coronary flow velocity reserve in diabetes mellitus patients with a negative coronary angiogram

BACKGROUND: Structural and functional abnormalities of the aortic wall and disturbances of the coronary circulation with presumed microvascular complications have been reported in patients with diabetes mellitus. OBJECTIVES: To simultaneously establish the coronary flow velocity reserve (CFVR) and aortic distensibility indexes in type 2 diabetes mellitus patients who have normal epicardial coronary arteries by stress transesophageal echocardiography (STEE). METHODS: The elastic properties of the descending aorta and the CFVR were evaluated simultaneously in 18 type 2 diabetes mellitus patients who had negative coronary angiograms. These results were compared with those of 21 nondiabetic subjects with normal epicardial coronary arteries and 24 patients with left anterior descending coronary artery (LAD) stenosis. STEE was used for the evaluation of elastic moduli of the descending aorta. The CFVR was calculated as the ratio of the average peak diastolic flow velocity during hyperemia to that at rest. RESULTS: The CFVR of diabetic patients with normal epicardial coronary arteries and those with LAD stenosis was similarly decreased compared with the controls (2.10+/-0.63 and 1.78+/-0.47 versus 2.76+/-1.25, P<0.05 and P<0.001, respectively). The elastic modulus (in 103 mmHg) was similarly increased in patients with diabetes mellitus and normal epicardial coronary arteries, and in those with LAD stenosis, compared with the control subjects (0.94+/-0.82 and 0.91+/-0.59 versus 0.49+/-0.19, P<0.05 and P<0.05, respectively). CONCLUSIONS: It may be stated that reduced aortic distensibility (increased elastic modulus) and the CFVR were demonstrated simultaneously during STEE in diabetic patients compared with nondiabetic subjects with negative coronary angiograms.     

Röntgendensitometrische Messung der myokardialen Perfusionsreserve bei symptomatischen Patienten ohne angiographisch detektierbare Koronarstenosen

BACKGROUND: Patients with typical angina pectoris but without coronary artery disease (CAD) are distinct in clinical aspects. In only few patients no abnormality is detected. Most present at least one or more cardiovascular risk factors and/or signs of myocardial ischemia. As previous studies have shown, the coronary flow reserve is reduced in most of these cases. Regional measurements of the coronary flow reserve, performed by different approaches, have shown a profound variation in different myocardial areas. It is not yet clear, whether this heterogeneity is physiological or due to a pathologic process. PATIENTS AND METHODS: The aim of this study was the regional measurement of the myocardial perfusion reserve in patients without epicardial coronary stenoses using X-ray densitometry. RESULTS: The myocardial perfusion reserve (MPR) for all patients in the coronary artery territories was 1.6 +/- 0.5 (LAD), 2.0 +/- 0.7 (RCx), and 2.2 +/- 0.6 (RCA). In hypertensive patients the MPR was significantly lower in all territories compared to normotensive patients (1.5 +/- 0.3 vs. 2.2 +/- 0.7 [LAD], 1.8 +/- 0.5 vs. 2.5 +/- 0.7 [RCx], 2.1 +/- 0.5 vs. 2.5 +/- 0.9 [RCA]). The rise time (AT) is inversely proportional to the perfusion. At rest it was significantly shorter in hypertensive patients compared to normotensive patients (5.0 +/- 1.0 s vs. 6.5 +/- 2.0 s [LAD], 4.8 +/- 1.1 s vs. 6.1 +/- 2.6 s [RCx], 5.9 +/- 1.4 s vs. 7.8 +/- 4.0 s [RCA]), while there was no difference at maximum papaverine-induced hyperemia. A statistical correlation between MPR and wall thickness was found only for the LAD area. The heterogeneity of perfusion under basal flow conditions was more pronounced in normotensive than in hypertensive patients, while under maximal hyperemia there was no detectable difference. There was no statistically significant correlation between the semiquantiative wash-in counts of myocardial scintigraphy and MPR. CONCLUSION: In this group of symptomatic patients MPR is lower than the lower limit of normal MPR, which is 3 in healthy individuals according to the literature. Patients with known arterial hypertension show a more severely impaired MPR which is especially pronounced in the LAD area and can be explained by a higher perfusion at rest. According to the authors' approach X-ray densitometry in the setting of coronary angiography is feasible and cost-effective to obtain information about the microvasculature.     

Impaired endothelium-dependent vasodilation in the brachial artery in variant angina pectoris and the effect of intravenous administration of vitamin C

Endothelial dysfunction in the coronary artery contributes to the pathogenesis of variant angina, and endothelial dysfunction in variant angina may be associated with increased oxidant stress in the systemic arteries. We investigated whether endothelial dysfunction exists in the peripheral artery in patients with variant angina, and also examined the effect of vitamin C, an antioxidant, on endothelium-dependent vasodilation. Using high-resolution ultrasound, both the flow-mediated vasodilation (FMD, endothelium-dependent vasodilation) and sublingual nitroglycerin-induced vasodilation (NTG-D, endothelium-independent vasodilation) in the brachial artery were measured in 28 patients with variant angina and 24 control subjects who had normal coronary arteries. FMD was significantly impaired in patients with variant angina compared with control subjects (1.8 +/- 2.2% vs 6.4 +/- 4.9%, p <0.001). FMD and NTG-D before and after intravenous administration of either vitamin C or placebo were measured in 17 patients with variant angina. FMD significantly improved after the administration of vitamin C (from 2.2 +/- 2.4% to 4.5 +/- 1.6%, p <0.01), but not after administration of the placebo (from 2.0 +/- 2.6% to 1.7 +/- 1.9%). The improved FMD due to vitamin C in patients with variant angina, however, was not significantly different from that in the control subjects. NTG-D was not significantly different between patients with variant angina and control subjects (14.0 +/- 7.8% vs 13.6 +/- 5.0%) and it was also not affected by vitamin C. In conclusion: (1) FMD in the brachial artery is impaired in patients with variant angina, and (2) the acute administration of the antioxidant, vitamin C, was observed to reverse this endothelial dysfunction. These findings support the theory that the systemic inactivation of nitric oxide due to oxidative stress might exist in patients with variant angina.     

Angiotensin type 1 receptor antagonism reverses abnormal coronary vasomotion in atherosclerosis

OBJECTIVES: This study was performed to determine whether angiotensin type 1 (AT1) receptor inhibition improves abnormal coronary vasomotion and endothelial dysfunction in patients with atherosclerosis or its risk factors. BACKGROUND: Endothelial dysfunction, an early feature of atherosclerosis, contributes to abnormal vasomotion during stress. Angiotensin II may contribute to endothelial dysfunction in atherosclerosis. METHODS: In 25 patients, mean age 59 +/- 2 years, with atherosclerosis or its risk factors, we measured coronary vasomotion during flow-mediated dilation (FMD) in response to adenosine, cold pressor test (CPT) and exercise before and after AT1 receptor blockade with intracoronary losartan (5 mg). RESULTS: Losartan did not alter resting coronary vascular tone, but epicardial FMD improved from 5.6 +/- 1.5% to 8.9 +/- 1.8% (p = 0.02). Abnormal epicardial vasomotion during CPT and exercise also improved with losartan from -1.7 +/- 0.8% to 1.5 +/- 0.1% (p = 0.02) and -0.6 +/- 0.9% to 3.4 +/- 1.2% (p = 0.009), respectively. Improvement in epicardial vasomotion was most prominent in segments with baseline endothelial dysfunction evidenced as constriction during stress. Microvascular dilation during adenosine, an endothelium-independent response, was unchanged with losartan. CONCLUSIONS: Inhibition of the coronary vascular AT1 receptors in patients with atherosclerosis improves epicardial vasomotion during stress, probably by improving endothelial dysfunction. Whether AT1 receptor blockade will provide long-term therapeutic benefits in atherosclerosis needs further investigation.     

Differential coronary artery calcification detected by electron beam computed tomography as an indicator of coronary stenosis among patients with stable angina pectoris.

BACKGROUND: The detection of coronary artery calcification by electron beam computed tomography (EBCT) has been suggested as an indicator of atherosclerosis and coronary artery disease (CAD). There is no consensus on the correlation between coronary calcification and angiographically significant stenosis on an artery-by-artery basis. OBJECTIVE: To examine the relationship between coronary calcification score (CCS) and the presence of significant CAD on an artery-by-artery basis in patients with stable angina pectoris. METHODS AND RESULTS: EBCT and coronary angiogram (CAG) were evaluated in 71 patients with stable angina and in nine control subjects. The CCSs of each of the four major coronary arteries were highest in patients with significant CAD (n=43), followed by patients with insignificant CAD (n=5), patients with syndrome X (n=23) and control subjects, respectively. Calcification scores of the four major coronary arteries appeared to have different predictive power for significant stenosis on the same vessel. For left main (LM) and left anterior descending (LAD) coronary arteries, CCSs of vessels with significant stenoses were not different from those without significant stenoses (values expressed as medians: LM 0 versus 1; LAD 98.5 versus 70; not significant). Calcification scores of left circumflex (LCX) and right coronary arteries (RCA) were significantly higher in vessels with significant stenosis (LCX 49.5 versus 0; RCA 53 versus 1; P<0.05). CCSs appeared to be moderately useful to predict significant stenoses in these two vessels (areas under receiver operating characteristic curves: LCX 0.68+/-0.08, 95% CI 0.52 to 0.81; RCA 0.71+/-0.08, 95% CI 0.55 to 0.84). CONCLUSIONS: The CCSs of RCA and LCX arteries, but not those of LM and LAD arteries, may predict significant angiographic stenosis on an artery-by-artery basis among patients with stable angina pectoris.     

Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease

OBJECTIVE: Flow-mediated, endothelium-dependent dilatation (FMD) of the coronary and peripheral circulation is impaired by increased oxidative stress in patients with coronary artery disease (CAD). Carvedilol is a novel beta-blocker that also shows an antioxidant effect in vitro. However, the effect of carvedilol on endothelial dysfunction associated with established coronary atherosclerosis has not been examined in the clinical setting. METHODS: We studied 29 patients with CAD, including 17 with recent myocardial infarction and 12 with stable effort angina pectoris. Nineteen patients received carvedilol (10 with infarction and 9 with angina), and 10 were treated with placebo (7 with infarction and 3 with angina). We also studied 13 age- and sex-matched control subjects. Brachial FMD during reactive hyperemia and nitroglycerin-induced, endothelium-independent dilatation were assessed by high-resolution ultrasound. RESULTS: FMD was smaller in patients with CAD compared with controls, although nitroglycerin-induced dilatation was similar. Carvedilol significantly improved FMD after long-term treatment (5. 1% +/- 0.4% at baseline to 7.8% +/- 0.3% after 4 months; P <.01) but not after short-term treatment (5.1% +/- 0.4% at baseline to 5.0% +/- 0.7% after 2 hours). Placebo therapy had no effect on endothelial dysfunction. Neither carvedilol nor placebo had an effect on nitroglycerin-induced dilatation after short- and long-term treatment. Long-term carvedilol therapy also significantly decreased the plasma level of thiobarbituric acid-reactive substances compared with placebo (carvedilol, 5.8 +/- 0.4 nmol/mL to 4.6 +/- 0.3 nmol/mL, P <.01; placebo, 5.9 +/- 0.4 nmol/mL to 5.8 +/- 0.4 nmol/mL, P = not significant). CONCLUSION: These findings suggest that the improvement of endothelial function by carvedilol may be caused by its antioxidant activity.     

Amounts of coronary arterial narrowing by atherosclerotic plaque at necropsy in patients with lower extremity amputation.

In 26 patients (mean age at death 68 +/- 9 years) who had undergone amputation (at mean age 63 +/- 12 years) of 1 or both lower extremities due to severe peripheral arterial atherosclerosis, the amounts of narrowing at necropsy in the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries were determined. During life, 15 of the 26 patients (58%) had symptoms of myocardial ischemia: angina pectoris alone in 1, acute myocardial infarction alone in 5, and angina and/or infarction plus congestive heart failure or sudden coronary death in 9. Twelve of the 26 patients (42%) died from consequences of myocardial ischemia: acute myocardial infarction in 5, sudden coronary death in 3, chronic congestive heart failure in 3, and shortly after coronary bypass surgery in 1. Grossly visible left ventricular necrosis or fibrosis, or both, was present in 21 patients (81%). Of the 26 patients, 24 (92%) had narrowing 76 to 100% in cross-sectional area of 1 or more major coronary arteries by atherosclerotic plaque. The mean number of coronary arteries per patient severely (> 75%) narrowed was 2.3 +/- 1.0/4.0. Of the 104 major coronary arteries in the 26 patients, 60 (58%) were narrowed > 75% in cross-sectional area by plaque. The 4 major coronary arteries in the 26 patients were divided into 5-mm segments and a histologic section, stained by the Movat method, was prepared from each segment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased TIMI frame counts in cocaine users: a case for increased microvascular resistance in the absence of epicardial coronary disease or spasm

BACKGROUND: Cocaine produces adverse cardiovascular effects, some of which cannot be explained by epicardial coronary artery disease (CAD) or spasm. HYPOTHESIS: The hypothesis of this study was that cocaine users would have increased coronary microvascular resistance, even in the absence of recent myocardial infarction (MI), CAD, or spasm. METHODS: Microvascular resistance was assessed by the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (cTFC) method in a consecutive series of 59 cocaine users without acute or recent MI or angiographically significant epicardial stenosis (> 50%) or spasm. The cTFCs in these patients were compared with 21 normal controls and with published normal cTFC values. RESULTS: The cTFC was significantly elevated (by 26-54%) in cocaine users. The cTFCs in the left anterior descending (LAD), circumflex (LCx), and right coronary (RCA)arteries in cocaine users were 30.0 +/- 10.9,34.1 +/- 11.5, and 28.6 +/- 11.8, respectively, compared with values in normal controls of 21.3 +/- 4.3 (p = 0.001), 24.4 +/- 7.2 (p = 0.001), and 22.7 +/- 5.1 (p = 0.04), respectively, and published normal cTFC values (all p < 0.01). An abnormally high cTFC was present in 61% of patients in the LAD, 69% in the LCx, and 47% in the RCA. CONCLUSIONS: Markedly decreased coronary blood flow velocity, indicating increased microvascular resistance, is present in cocaine users, even in the absence of acute or recent MI, or significant epicardial CAD or spasm. Increased microvascular resistance may explain many important cardiovascular manifestations of cocaine use and has therapeutic implications. Slow coronary filling may also suggest the possibility of cocaine use in patients in whom it was not otherwise suspected.     

Effects of calcitonin gene-related peptide on normal and atheromatous vessels and on resistance vessels in the coronary circulation in humans

BACKGROUND. Calcitonin gene-related peptide (CGRP) is a potent dilator of normal epicardial coronary vessels in humans, but its effects on myocardial blood flow and atheromatous coronary vessel diameter are unknown. METHODS AND RESULTS. Seven patients were entered for study of the effects of CGRP on coronary blood flow and 13 for the comparison of its effects on normal and atheromatous coronary arteries. In the first seven patients, left anterior descending artery (LAD) diameter at an angiographically normal site, coronary sinus oxygen saturation (CSO2S), systemic blood pressure, and heart rate were measured during intracoronary infusion of increasing concentrations of CGRP (up to 200 ng/ml at 2 ml/min) followed by intracoronary adenosine (0.267 micrograms/ml at 2 ml/min) and finally intracoronary glyceryl trinitrate (GTN) (5 micrograms/ml at 2 ml/min). CGRP dilated the normal segment of the LAD by 22.6 +/- 8% (mean +/- 95% confidence interval), p less than 0.001, with only a small increase in CSO2S from 40.1 +/- 2.7% to 47.3 +/- 2.7%, p less than 0.001. Adenosine, a potent dilator of myocardial resistance vessels, caused no further increase in LAD diameter but caused a rise in CSO2S from 47.3 +/- 2.7% to 76.0 +/- 2.7%, p less than 0.001. GTN caused no further increase in LAD diameter. As heart rate-blood pressure product remained unchanged throughout the study, the increase of CSO2S indicated only a small increase in myocardial blood flow after CGRP infusion. In 13 patients with atheromatous coronary artery disease, the effects of intracoronary CGRP at angiographically normal sites, stenoses, angiographically normal sites immediately adjacent to stenoses, and sites of coronary artery wall irregularity were compared after intracoronary infusion of a single dose of CGRP (200 ng/ml at 2 ml/min) followed by intracoronary GTN (5 micrograms/ml at 2 ml/min). At these four sites, CGRP resulted in dilatation by 17.0 +/- 5.6%, 15.3 +/- 12.1% (NS), 7.6 +/- 5.4% (NS), and 15.9 +/- 7.8%, respectively. There was no significant further dilatation after GTN at any of the four sites. CONCLUSIONS. These data indicate that CGRP has little effect in humans at rest on coronary resistance vessels in nonischemic myocardium but causes marked dilatation of normal arteries and variable dilatation of atheromatous epicardial arteries.     

Coronary hemodynamics in vasospastic angina: quantitative analysis by digital subtraction angiography

To evaluate the coronary circulation and myocardial perfusion dynamics, we performed left coronary digital subtraction angiography (DSA) in 35 patients with vasospastic angina. The left coronary circulation time (CCT) measured from the proximal left coronary artery to the coronary sinus was 5.77 +/- 0.86 sec, and the left epicardial conducting artery transmission time (CAT) measured from the proximal left coronary artery to the apical area was 2.65 +/- 0.82 sec in normal controls. The CCT and CAT were significantly prolonged in patients with vasospastic angina, indicating that the coronary peripheral vascular resistance is probably greater after the cessation of nitrates and Ca(++)-antagonists. After the intracoronary injection of ergonovine malate, the CCT was slightly shortened, but the apical T1/2 was significantly prolonged in patients with vasospastic angina. This suggested that coronary vasospasm is present not only in the epicardial arteries but also in coronary arteries with peripheral resistance. These phenomena were not observed in normal controls. We performed left coronary DSA after conventional left coronary cineangiography. When the CCT exceeded 6.7 sec, we considered that the coronary circulation was significantly impaired. We concluded that the coronary DSA is very useful for evaluating abnormal coronary circulation in patients with vasospastic angina during myocardial perfusion.     

Protective effect of high density lipoprotein on endothelium-dependent vasodilatation

Low concentrations of high-density lipoprotein cholesterol (HDL-C) have been associated with increased risk of coronary heart disease (CHD) even when the total cholesterol (TC) and triglyceride (TG) levels are not elevated. The mechanism by which HDL confers protection against atherosclerosis remains speculative. Using high-resolution ultrasound, we measured the dilatation changes of brachial arteries during reactive hyperemia and after sublingual glyceryl trinitrate (GTN) in 63 patients with established (CHD) and 45 controls, in which the serum TC level was normal. The results showed that both flow-mediated dilatation (FMD) and GTN-induced dilatation of brachial arteries in patients with CHD were much reduced compared with control group (2.31+/-2.46% vs. 7.43+/-4.10% and 16.41+/-6.15% vs. 22.44+/-8.63%, respectively, P<0.001 for all). Univariate analysis indicated that FMD of brachial arteries was inversely related to age (r=-0.226, P<0.05), hypertension (r=-0.229, P<0.05), baseline diameter (r=-0.299, P<0.01) and LDL-C (r=-0.237, P<0.05) and positively related to HDL-C (r=0.491, P<0.01). GTN induced vasodilatation was inversely related to age (r=-0.216, P<0. 05) and baseline diameter (-0.476, P<0.01). Multiple stepwise regression analyses in two groups taken together showed that HDL-C and age were the independent predictors of the FMD of brachial arteries (beta=0.466, P=0.000 and beta=-0.184, P=0.020, respectively). Baseline diameter was significant predictor of GTN-induced vasodilatation (beta=-0.390, P=0.000). The analysis in the group of CHD patients showed that only HDL-C was significantly relate to the FMD of brachial arteries (beta=0.295, P=0.018 ) and in controls that hypertension and HDL-C were significantly relate to the FMD of brachial arteries (beta=-0.395, P=0.004 and beta=0.344, P=0.011, respectively). These finding suggest that endothelium-dependent and endothelium-independent vasodilatation are impaired in the patients with CHD. HDL exerts a protective effect on endothelium-dependent vasodilatation in TC being relatively normal population.     

Does isolated myocardial bridge really interfere with coronary blood flow?

BackgroundMyocardial bridge (MB) is defined as a segment of a major epicardial coronary artery the “tunneled artery” that goes intramurally through the myocardium beneath the muscle bridge. Multiple methods have been proposed to assess coronary flow rate among which thrombolysis in acute myocardial infarction frame count was a relatively new semiquantitative method.ObjectivesOur goal was to determine incidence of MB in the patients undergoing coronary angiography in Mansoura Specialized Hospital, Cardiac Catheterization Laboratory, also to investigate the hypothesis that slow coronary flow rate may be linked to angina or angina like symptoms in patients with MB without stenotic lesions in epicardial coronary arteries using TFC.Patients and methodsFifteen patients with MB (group I) were retrospectively collected from Mansoura Specialized Hospital, Cardiac Catheterization Laboratory, we review 3000 cases referred to diagnostic coronary angiography to exclude significant coronary artery disease. Fifteen patients with normal coronary angiography served as control (group II). We review the clinical presentations, risk factors, echocardiographic data for both test and control groups. TFC was calculated using a simple continuous index.ResultsThe incidence of MB in our study was 0.5%. CTFC in LAD was significantly higher in the patients with MB compared with control. No significant correlation between TFC and echocardiographic parameters.ConclusionsMyocardial bridging must be considered especially in patients at low risk for coronary atherosclerosis but with angina like chest pain or established myocardial ischemia. We suggest that coronary blood flow is decreased in the patients with MB compared with the patients having normal coronary.     

Myocardial bridge (MB): an angiographic curiosity?

The coronary angiograms of 1,500 cases performed between 1981 and 1989 were analysed to find out the incidence of Myocardial Bridge (MB) and its significance as regards myocardial ischemia. Sixteen of these (1.06%) were found to have MB. Their ages ranged from 27-70 years (m = 49.2) and male:female ratio was 13:3. Out of 16 patients, 7 (group A) had associated coronary artery disease (CAD) (7 of 1421; 0.49%) and remaining 9 (group B) had no associated CAD (9 of 79; 11.39%). All the MB were found on left anterior descending artery (LAD) (3 on proximal LAD and 13 on mid LAD). No MB was found on right coronary artery (RCA) or circumflex arteries. The location of the MB did not affect the pattern of CAD. Chronic stable angina was the commonest presenting symptom in group A patients (5 out of 7) and atypical angina in group B patients (5 out of 9). Majority of group B patients had either normal or nonspecific ST-T changes in ECG (7 out of 9). However, the presence of previous myocardial infarction or ECG evidence of 'Q' wave infarction (2 out of 2) was always associated with significant CAD. Similarly, regional wall motion abnormalities on echocardiogram were always found in patients with significant CAD and old myocardial infarction. All 9 patients with MB and normal coronary arteries were managed conservatively with good relief of symptoms, whereas other seven patients were managed on the merits of the underlying CAD. In conclusion, the MB is a normal variant found incidentally on coronary angiography, and does not have any definite clinical correlations or pathological significance.     

Impaired endothelial function in patients with myocardial bridge

OBJECTIVE: The relationship between myocardial bridging (MB) and ischemic heart disease is still controversial. In this study, we aimed to evaluate the existing atherosclerosis and noninvasive endothelial function of brachial artery in patients with MB. METHODS: The present study included 50 patients (group I) who had MB in left anterior descending (LAD) on coronary angiography. All of the coronary artery segments were evaluated by intravascular ultrasound (IVUS). Endothelial function was assessed with measurement of flow-mediated dilatation (FMD) and nitrate-dependent dilatation in the brachial artery. The study also included 30 healthy control subjects (group II). Patients in the group I were further subdivided into two subgroups based on the findings on IVUS: group IA included 20 patients without atherosclerotic lesions and group IB included 30 patients with atherosclerotic coronary artery disease in addition to MB. RESULTS: FMD values were found to be significantly lower in the patients with MB (group I) than in the control (6.4 +/- 3% vs 11 +/- 4%, P <0.001). In regard to FMD values in subgroups, FMD was 7 +/- 2% in the group IA and 5.8 +/- 1% in the group IB (P = 0.023). On IVUS, atherosclerotic plaque was found proximal to the bridge in the same coronary artery segment in addition to MB in 75% of the patients in group I (group IB). No atherosclerotic plaque was found in within or distal segments of MB. CONCLUSION: Endothelial function is impaired in patients with MB and there is an increased tendency for atherosclerosis proximal to the bridge in the patients with MB. Endothelial dysfunction is more severe in the patients with atherosclerosis proximal to the bridge.     

Dysfunction of the coronary microcirculation in type 2 diabetic patients

A failure of coronary blood flow to increase during cold pressor test has been shown in patients with coronary atherosclerosis and impaired metabolic coronary vasodilatation in response to atrial pacing has been demonstrated in diabetic patients without significant epicardial artery stenoses. This study was designed to evaluate coronary microvascular adaptation to increased myocardial oxygen demand in response to sympathetic stimulation in diabetic patients with angiographically normal coronary arteries. Microvascular coronary adaptation to increased myocardial oxygen demand due to sympathetic stimulation evoked by the cold pressor test has been examined in 22 type 2 diabetic patients and in 15 control subjects with angiographically normal coronary arteries and no other risk factors. Coronary blood flow was calculated by measuring mean flow velocity in left anterior descending coronary artery by intracoronary Doppler and cross sectional area of the artery by digital angiography. Results show that despite a similar increase in rate-pressure product in the 2 groups (+22.6 +/- 12.4% in diabetic patients and +31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in left anterior descending artery was significantly lower in diabetic patients than in control subjects (+14.7 +/- 19.8% vs +75.5 +/- 13.5%, respectively, p = 0.0001). In addition, when there was a positive correlation between the 2 parameters in control subjects (R = 0.651, p < 0.01), there was no relationship in diabetic patients (R = 0.054). In conclusion, this study demonstrates that vasodilatation of coronary microcirculation in response to sympathetic stimulation evoked by cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilatation during current life stress episodes such as exercise, mental stress or cold exposure.     

Myocardial bridge: a bridge to atherosclerosis.

OBJECTIVE: Myocardial bridge (MB) is a congenital anomaly characterized by narrowing during systole of some of the epicardial coronary arterial segments running in the myocardium. Although, it is considered as a benign anomaly, it may lead to such complications as acute myocardial infarction, ventricular tachycardia, syncope, atrioventricular block and sudden cardiac death. In this study, we aimed to investigate demographic, clinical and angiographic characteristics of the patients with MB found on coronary angiography. METHODS: The present study included 71 patients with MB found on coronary angiographies performed in our institution between January 1999 and September 2003. Based on the findings on angiography, the patients were subdivided into group A (n=41) and group B (n=30). The patients in the group A had no atherosclerotic lesion and the patients in the group B had coronary artery disease in addition to MB. Angiographic, demographic and clinical characteristics of both groups were compared. RESULTS: There were no differences between two groups in distribution of gender and risk factors of coronary artery disease whereas mean age of the patients in the group A was lower (47+/-5 years vs 55+/-11 years, p=0.01). Frequency of two or more risk factors for coronary artery disease in a particular patient was significantly higher in the group B (55% vs 30%, p=0.03). Myocardial bridge was located at proximal or mid segments of left anterior descending artery (LAD) in 40 patients whereas its presence in both LAD and right coronary artery was found only in one patient in group A. Mean bridging percent was 43+/-27% in group A. Localization of MB was LAD in 29 patients of group B. One patient with severe aortic valve stenosis in this group had MB at first septal branch. Mean bridging percent was 70+/-25% in group B, which was significantly higher than in group A (p<0.05). Atherosclerotic narrowing developed in only LAD in 14 patients, LAD and other vessels in 7 patients and in the vessels without MB in 9 patients. In patients with MB in LAD atherosclerotic narrowing of vessel developed proximally to the MB. Clinically, stable angina pectoris was seen more frequently in group A than group B (70% vs 35%, p=0.01), whereas the frequency of acute coronary syndrome was higher in group B (65% vs 30%, p=0.04). In regard to therapeutic approach, more patients in the group A received medical management (80% vs 50%, p=0.01), while more patients in the group B underwent surgical and percutaneous interventions (50% vs 18%, p=0.04). CONCLUSION: Myocardial bridge probability should be considered in young patients presenting with angina or if the same symptoms are persistent in the patients without more than one risk factor for coronary artery disease. Myocardial bridge may initiate the development of atherosclerotic lesion or may facilitate progression of atherosclerosis in the proximal segment of the vessel. The risk of acute coronary syndrome rises when atherosclerosis is superimposed on MB. Myocardial bridge should be considered in the young patients, presenting with angina or its equivalents without atherosclerotic lesions on coronary angiography.     

Cardiac imaging and myocardial kinetics of technetium-tertiary butyl-isonitrile during dipyridamole-induced hyperemia

To determine the myocardial kinetics of technetium-tertiary-butyl-isonitrile (Tc-TBI) during dipyridamole-induced hyperemia, the circumflex coronary arteries (LCX) of 15 dogs were partially occluded. Dipyridamole was then infused intravenously over 4 minutes, creating hyperemic flows in the anterior descending (LAD) coronary system. Tc-TBI was administered, then LAD and LCX regional myocardial Tc-TBI activities were continuously monitored with miniature detectors and gamma camera imaging over 3 hours. Microsphere-determined regional myocardial blood flows demonstrated an LCX/LAD flow ratio of 0.81 +/- 0.21 at rest and 0.45 +/- 0.24 (SD) during dipyridamole infusion. Three-hour fractional Tc-TBI clearance rates were minimal and were equal in the LAD (0.14 +/- 0.11) and LCX (0.13 +/- 0.12) zones (p = ns). Excellent gamma camera images, demonstrating the LCX defect, were obtained in all dogs. The correlation coefficient was 0.98 for regional myocardial blood flow vs initial Tc-TBI distribution. In conclusion: (1) Dipyridamole vasodilation unmasked coronary stenoses despite no flow disparities at rest. (2) The initial distribution of Tc-TBI is proportional to regional myocardial blood flow. (3) There is minimal washout and no redistribution into the initial defect over time, and thus image quality is stable over time. (4) Tc-TBI myocardial kinetics may be applicable to closely related agents currently being developed.     

Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans

Studies in animals have suggested that increases in blood flow result in dilation of large arteries by an endothelium-dependent mechanism. Atherosclerosis can impair endothelium-dependent vasodilation to vasoactive agents. The purpose of this study was to determine whether or not large coronary arteries in humans exhibit dilation with increases in blood flow and to test the hypothesis that this response is impaired in the presence of atherosclerosis. Graded concentrations of adenosine were infused into the distal left anterior descending (LAD) coronary artery to test the dilator response of the proximal LAD to increases in blood flow. The proximal LAD was thereby exposed to changes in blood flow, but not directly to adenosine. Ten patients with angiographically smooth proximal LAD segments (group 1) and seven patients with irregularities in the proximal LAD consistent with mild atherosclerosis (group 2) were studied. Infusions of adenosine throughout the range of 0.022 to 2.2 mg/min into the LAD produced a dose-dependent increase in estimated coronary blood flow and a mean increase of 305 +/- 27% at 2.2 mg/min adenosine. At 2.2 mg/min adenosine, a striking difference (p less than 0.001) occurred between the significant flow-mediated dilation of the proximal LAD observed in group 1 (+13.2 +/- 1.3% from 2.63 +/- 0.16 mm, p less than 0.001), and the lack of dilation in group 2 (+1.8 +/- 1.5% from 3.20 +/- 0.17 mm, p = NS), despite a greater increase in coronary blood flow in group 2 (+387 +/- 29%) than in group 1 (+230 +/- 36%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired endothelium-dependent cholinergic coronary vasodilation in patients with angina and normal coronary arteriograms.

The coronary vasomotor responses to selective infusion of graded concentrations (10(-6) to 10(-4) M) of acetylcholine into the left anterior descending artery were assessed by quantitative coronary arteriography in 24 patients with normal coronary arteriograms (12 patients with atypical symptoms and 12 patients with typical anginal pain) and 36 patients with coronary artery disease with different degrees of atherosclerosis of the left anterior descending artery. In the patients with normal coronary arteries and atypical chest pain, acetylcholine induced predominantly a vasodilator response, which was maximal during a 10(-5) M acetylcholine infusion. In contrast, in patients with coronary artery disease, acetylcholine caused dose-dependent vasoconstriction, which was observed even if the left anterior descending artery itself was smooth. Marked vasoconstriction was also induced in the patients with typical anginal pain and angiographically normal coronary arteries. In nine of these patients, this constrictor response was associated with anginal pain and electrocardiographic evidence of myocardial ischemia. Intracoronary administration of isosorbide dinitrate (1 mg) relieved the anginal pain and dilated all vessels. These data suggest that 1) patients with normal coronary arteriograms and angina pectoris manifest impairment of endothelium-dependent vasodilation similar to that observed in patients with overt coronary atherosclerosis; and 2) abnormal coronary vasoconstrictor responses resulting from this impairment may contribute to the pathogenesis of myocardial ischemia and angina in these patients.