Epicardial Coronary Arteries In Patients Research Articles

Vitamin C attenuates abnormal vasomotor reactivity in spasm coronary arteries in patients with coronary spastic angina

Objectives. This study sought to examine effect of vitamin C, an antioxidant, on the abnormal vasomotor reactivity in spasm coronary arteries.Background. Oxygen free radicals generated in the arterial walls have been shown to cause endothelial vasomotor dysfunction.Methods. Responses of the epicardial arterial diameters of the left coronary arteries to the intracoronary infusion of acetylcholine (ACh) (10 and 50 μg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of vitamin C (10 mg/min) or saline as a placebo in 32 patients with coronary spastic angina and in 34 control subjects.Results. Vitamin C infusion suppressed the constrictor response of the epicardial diameter to ACh in spasm coronary arteries but had no significant effect in the control coronary arteries (percent change in distal diameter in response to 10 μg/min of ACh [constriction (−), dilation (+), mean ± SEM] before vitamin C: −8.2 ± 2.9% in spasm arteries, +8.4 ± 2.9%∗ in control arteries; during vitamin C: +0.2 ± 3.8%∗ in spasm arteries, +7.2 ± 1.3%∗ in control arteries [∗p < 0.01 vs. spasm arteries before vitamin C]). The coronary sinus–arterial difference in plasma thiobarbituric acid reactive substances during ACh infusion, an indicator of lipid peroxidation in coronary circulation, was higher in patients with coronary spastic angina than in control subjects (p < 0.01) but was suppressed in patients with coronary spastic angina to comparable levels in control subjects by combined infusion of vitamin C. Saline infusion had no effect.Conclusions. The results indicate that vitamin C attenuates vasomotor dysfunction in epicardial coronary arteries in patients with coronary spastic angina. Oxygen free radicals may at least in part play a role in the abnormal coronary vasomotor reactivity in response to ACh in spasm coronary arteries.

The diameter of the epicardial coronary arteries in patients with dilated cardiomyopathy

We investigated the diameter of epicardial coronary arteries in 12 patients (ten men) with dilated cardiomyopathy, and compared to 21 normal persons (14 men). Dilated cardiomyopathy patients were younger than controls with no difference in height, weight and body surface area. Ejection fraction was lower in dilated cardiomyopathy compared to normals (31±10% and 73±7%, respectively, P<0.001). Left ventricular mass was significantly larger (P=0.04). The sum of diameters of the proximal left anterior descending, circumflex and right coronary arteries (Total Coronary Diameter) in the dilated cardiomyopathy and controls was 13.4±2.7 and 10.5±1.5 mm (P<0.001). Absolute diameters of the left main, left anterior descending, circumflex, proximal right coronary artery and the right ventricular branch in dilated cardiomyopathy were also significantly larger as was Total Coronary Diameter adjusted for body surface area. Total Coronary Diameter adjusted for left ventricular mass, was significantly smaller (103.42±30.38, 146.00±41.59 mm/mg, respectively, P<0.03). Specific arteries in the dilated cardiomyopathy adjusted for left ventricular mass were significantly smaller, or had a tendency for smaller diameter compared to normals. There was no correlation between age and coronary diameter in each group. After adjusting for left ventricular mass there was no difference in coronary artery diameter between men and women. Thus, coronary arteries of patients with dilated cardiomyopathy have increased absolute diameter compared to normals, but decreased diameter when adjusted for left ventricular mass. This may contribute to patients' complaints and to the natural history of the disease.

Effects of inhibition of nitric oxide synthesis in patients with coronary artery disease and stable angina.

Inhibition of nitric oxide synthesis causes a decrease in the basal diameter of normal distal epicardial coronary arteries in normal subjects. The effects of inhibition of nitric oxide in atheromatous coronary arteries is unknown. This study assessed the effects of the inhibition of nitric oxide synthesis in epicardial coronary arteries in patients with coronary artery disease. The effects of an intracoronary infusion of NG-monomethyl-L-arginine (LNMMA, an inhibitor of nitric oxide synthesis), were studied in 13 patients with chronic stable angina and coronary artery disease. The diameter of angiographically normal proximal and distal segments and coronary stenoses was measured by quantitative angiography. In response to an LNMMA infusion of 16 mumol min-1 for 4 min there was a significant reduction (P < 0.01) in the luminal diameter of the distal segments of diseased arteries (from 1.32 +/- 0.07 to 1.17 +/- 0.06 mm) and at the site of stenosis (from 1.15 +/- 0.22 to 1.06 +/- 0.20 mm), but no change (P = NS) in the luminal diameter of the proximal segments (from 3.16 +/- 0.12 to 3.08 +/- 0.14 mm) of diseased arteries. The average effect of inhibition of basal nitric oxide synthesis in epicardial coronary arteries in patients with stable angina and coronary artery disease was only distal constriction. Coronary stenoses constricted at the highest LNMMA concentration.

Importance of Nitric Oxide in the Coronary Artery at Rest and During Pacing in Humans

Objectives. The purpose of this study was to investigate the role of endothelium-dependent vascular regulation in the human coronary circulation during rest and hyperemic states.Background. Evidence of the role of nitric oxide (NO) during metabolic demand is not consistent in animal and human coronary circulation.Methods. NG-Monomethyl-l-arginine (l-NMMA), a specific inhibitor of NO synthesis, was infused into the left anterior descending coronary artery at rest and during rapid atrial pacing in 18 subjects—9 with normal coronary arteries (control) and 9 with atherosclerotic coronary arteries. The diameter of the epicardial coronary artery was measured by quantitative coronary angiography. Vasodilation of the coronary microcirculation was assessed using an intracoronary Doppler FloWire.Results. Infusion of 25 μmol/min of l-NMMA reduced the diameter of the proximal and distal epicardial coronary artery segments by 8 ± 2% (mean ± SE) and 11 ± 2%, respectively (p < 0.05) in the control subjects. The coronary blood flow (CBF) decreased by 33 ± 13% during l-NMMA infusion. l-NMMA caused similar changes in the diameter of the distal epicardial segment and the CBF in patients with coronary artery disease. The proximal vessel diameter did not change significantly during infusion of l-NMMA. During pacing, infusion of l-NMMA caused the same changes in vessel diameter as before pacing in both groups, but did not affect CBF.Conclusions. Our findings indicate that NO synthesis maintains basal vasomotor tone in both conduit and resistance vessels in the normal human coronary circulation. Although NO release was impaired in the large epicardial coronary arteries in patients with atherosclerosis, NO still regulated vascular tone in the small epicardial coronary arteries and arterioles. Our results suggest that vasodilation in arterioles during increased myocardial oxygen demand is mediated by metabolic or myogenic mechanisms, or both, rather than by endothelium-dependent production of NO.(J Am Coll Cardiol 1997;29:85–92)>

Deficiency in nitric oxide bioactivity at spasm sites of epicardial coronary arteries in patients with coronary spastic angina

Deficiency in nitric oxide bioactivity at spasm sites of epicardial coronary arteries in patients with coronary spastic angina

Acute cholesterol lowering with LDL-apheresis improves endothelial function of the epicardial coronary artery in patients with hypercholesterolemia

Acute cholesterol lowering with LDL-apheresis improves endothelial function of the epicardial coronary artery in patients with hypercholesterolemia

Diffuse disorder of coronary artery vasomotility in patients with coronary spastic angina: Hyperreactivity to the constrictor effects of acetylcholine and the dilator effects of nitroglycerin

We examined the vasomotility of the entire epicardial coronary artery system in patients with and without coronary spastic angina. The coronary arteries of patients with variant angina are hyperreactive to diverse constrictor stimuli. It is unclear whether the abnormal responses to constrictive or dilative stimuli, or both, result from a localized or diffuse disorder in the coronary artery tree. Coronary artery diameter responses to intracoronary acetylcholine and nitroglycerin were examined at the proximal, middle and distal segments of three principal coronary arteries in 36 patients with coronary spastic angina without significant stenosis and in 12 young (< or = 30 years old) and 20 older control subjects (> 30 years old) with normal coronary arteriographic findings. In 10 patients with significant coronary stenosis, the responses of the prestenotic segments were also examined. In patients with coronary spastic angina, coronary spasm was induced in 23 left anterior descending, 13 left circumflex and 17 right coronary arteries by acetylcholine. Multivessel spasm was observed in 15 patients. Acetylcholine had a dilator effect on most segments in young control subjects and a mild constrictor effect in older control subjects and in patients with significant stenosis. Comparison of the responses to acetylcholine among groups demonstrated that the constrictor response of the artery with spasm was enhanced significantly and diffusely. That of the artery without spasm also tended to be enhanced. Coronary artery diameters after nitroglycerin did not differ in any segment among patients with coronary spastic angina and both control groups. In patients with coronary spastic angina, nitroglycerin significantly enhanced dilation in all segments of the artery with spasm compared with that observed in both control groups and in most segments of the artery without spasm. Patients with significant coronary stenosis had a reduced response compared with that in control subjects. Hyperreactive responses not only to the constrictor effects of acetylcholine, but also the dilator effects of nitroglycerin were detected diffusely in the epicardial coronary arteries of patients with coronary spastic angina. This finding indicates that a diffuse, not localized, disorder in vasomotility is involved in the pathogenesis of coronary spastic angina.

Systemic nature of endothelial dysfunction in atherosclerosis

Vascular endothelium plays a pivotal role in the maintenance of vasodilation and the inhibition of platelet aggregation and smooth muscle cell proliferation through the release of nitric oxide and other factors. Extensive data have demonstrated abnormalities in coronary endothelial function in the epicardial coronary arteries in patients with atherosclerosis or risk factors for atherosclerosis. This dysfunction leads to abnormal vasoconstriction and platelet aggregation, which likely play a role in producing ischemia in patients with coronary artery disease. Invasive techniques have been available to assess endothelium-dependent vasodilator responses in the coronary arteries. However, until recently little has been known about endothelial responses in the peripheral vasculature, as methods to assess this have not been readily available. The hypothesis that endothelial dysfunction is a systemic process is explored, and new noninvasive methods of assessing endothelial function are discussed.

931-114 Effects of Inhibition of Nitric Oxide Synthesis in Proximal and Distal Segments in Patients with Normal Arteries and in Patients with Coronary Artery Disease

Inhibition of nitric oxide synthesis causes a decrease in basal diameter of distal epicardial coronary arteries in patients (pts) with normal coronary arteries (NCA). The effects of inhibition of nitric oxide synthesis with NG-monomethylL-arginine (LNMMA) in atheromatous coronary arteries was evaluated in 13 pts with chronic stable angina (aged 57 ± 7 years, 11 males) due to angiographically documented coronary artery disease and in 8 pts (aged 50 ± 5 years, 4 males) with angiographically NCA. LNMMA was infused intracoronary at 4,8 and 16 μmol/min each for 4 minutes. In response to low LNMMA. 4 μmol/min, there was a significant (p &lt; 0.05) reduction in luminal diameter of both proximal (from 3.49 ± 0.28 to 3.35 ± 0.28 mm) and distal (from 1.33 ± 0.07 to 1.23 ± 0.06 mm) segments in patients with NCA. In patients with atheromatous arteries there was a reduction in diameter of the distal segments (from 1.44 ± 0.06 to 1.33 ± 0.07 mm) but no change occurred in the proximal segments (from 2.95 ± 0.16 to 2.89 ± 0.16 mm). In response to high LNMMA. 16μmol/min, there was a significant (p &lt; 0.01) reduction in luminal diameter of both proximallfrom 2.53 ± 0.27 to 2.33 ± 0.26 mm) and distal (from 1.10 ± 0.06 to 0.99 ± 0.06 mm) segments in the pts with NCA. In the pts with atheromatous arteries the distal segments decreased in diameter (from 1.32 ± 0.07 to 1.17 ± 0.06 mm) but no change occurred in the proximal segments (from 3.16 ± 0.12 to 3.08 ± 0.14 mm). The magnitude of the distal vessel constriction was similar in both the patients with normal and in those with atheromatous arteries (–9.6 ± 2.1% and –10.9 ± 2.6% respectively, p = NS). In conclusion in pts with chronic stable angina due to coronary artery disease inhibition of basal nitric oxide synthesis causes distal coronary artery vasoconstriction, but it has no effect on proximal segments

Alleviation of cocaine-induced coronary vasoconstriction by nitroglycerin

Cocaine induces vasoconstriction of epicardial coronary arteries in patients with and without coronary artery disease, and this vasoconstriction is particularly marked in segments narrowed by atherosclerosis. To assess the effect of nitroglycerin on cocaine-induced coronary vasoconstriction, computer-assisted quanitative analysis was performed on nondiseased and diseased coronary artery segments in 23 patients (18 men, 5 women, aged 43 to 65 years) 1) at baseline, 2) after administration of intranasal saline solution (in 8 patients) or 2 mg/kg of cocaine (in 15 patients), and then 3) after administration of sublingual placebo (in 6 patients) or 0.4 or 0.8 mg of nitroglycerin (in 9 patients) in the 15 patients given cocaine.In response to cocaine administration, coronary artery crosssectional area decreased 22 ± 7% (mean ± SD) in nondiseased segments (p < 0.05) and 45 ± 18% in diseased segments (p < 0.02). The magnitude of vasoconstriction was greater (p = 0.01) in the diseased segments. Sublingual nitroglycerin abolished the vasoconstriction in both nondiseased and diseased segments. Thus, nitroglycerin alleviates cocaine-induced vasoconstriction in patients with coronary artery disease.

Composition of atherosclerotic plaques in the four major epicardial coronary arteries in patients ≥ 90 years of age

The composition of atherosclerotic plaques in 733 five-mm segments of the 4 major (left main, legt anterior descending, left circumflex and right) epicardial coronary arteries of 18 patients ≥90 years of age was determined by computerized planimetric analysis. By analysis of all coronary segments of all patients >90, the plaques consisted primarily of fibrous tissue (87 ± 8%) with calcific deposits (7 ± 6%), pultaceous debris (5 ± 4%) and foam cells (1 ± 1%) occupying a much smaller percentage of plaque area. Analysis of composition according to the 4 degrees of luminal cross-sectional area narrowing revealed marked step-wise increases in pultaceous debris (from 0 ± 0% at 0 to 25% narrowing to 18 ± 22% at 76 to 100% narrowing, p = 0.0001) and calcific deposits (from 0 ± 0 to 10 ± 15%, p = 0.002), and decreases in fibrous tissue (from 99 ± 3 to 71 ± 23%, p = 0.0001) and area occupied by the media (from 35 ± 8 to 16 ± 8%, p = 0.0001). When the analysis was restricted to sections narrowed >75%, no significant differences were found in plaque components or medial area between patients with (11 patients) and without (7 patients) myocardial infarcts at necropsy.

Percutaneous Transluminal Coronary Angioplasty:: Morphological findings in 3 patients

Little morphologic information is available on the status of the major epicardial coronary arteries in patients dying after percutaneous transluminal coronary angioplasty. We studied hearts from 3 men (aged 60, 45 and 47 years) dying 3 days, 1 month and 7 months after balloon--dilatation of obstructed coronary artery segments. Twice the left anterior, once the left main coronary artery have been desobliterated. In one patient the procedure has not been successful and a venous bypass graft had to be implanted. Histologically the site of dilatation is clearly recognisable after 7 months. The characteristic findings are intimal tears in the segment opposite to the obstructing plaque. The intimal gaps are filled after 7 months by a neointima. In the dilated left main coronary we find 1 month after angioplasty an extensive proliferation of smooth muscle cells resulting in restenosis. Two patients died suddenly after an interval without angina. In the third patient--ome hours after bypass grafting--spasm of the non-involved right coronary artery occurred resulting in inferior infarction; this patient died 3 days after dilatation.

Analysis of coronary responses to nifedipine alone and in combination with intracoronary nitroglycerin in patients with coronary artery disease

Left coronary artery (CA) dilation responses to nifedipine and nitroglycerin (NTG) were studied in patients with CA disease. Quantitative angiography was used to measure the diameter of CAs before and after nifedipine (10 mg buccal) and the addition of NTG (200 μg) given into the left CA. Ninety-three CA segments were measured. The CA diameter was unchanged in 60 segments after nifedipine and was increased in only 27. Diameters of six other segments decreased. The average percentage of dilation of the various CA segments after nifedipine ranged from −2% to 14%. After NTG, CA dilation compared with control diameters occurred in 84 of the 93 segments. Only eight CA segments were unchanged and one other decreased. The average percentage of dilation of the various CA segments after NTG ranged from 8% to 35% compared with control diameters. Compared with diameters observed after nifedipine, NTG caused dilation in 82 of 93 CA segments; 10 appeared unchanged and one decreased. The diameter of eight coronary stenoses was also measured and was increased in three after nifedipine. After NTG the diameter of six of the eight stenoses increased compared with control diameter, and in four of the six that showed dilation, the diameter was larger than after nifedipine alone. These data suggest that nifedipine does not cause appreciable dilation of epicardial CA in patients with coronary disease. The capacity of NTG to induce dilation appears preserved after nifedipine. Although dilation of epicardial CAs and coronary stenoses was not apparent after nifedipine in our patients at rest, it is possible that nifedipine's clinically beneficial effects are mediated in some patients through prevention of increases in coronary tone.