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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little is known of the clinical significance of myocardial bridges, which may be recognized angiographically as systolic coronary artery narrowing (SCAN). A retrospective review of a 1 year's experience (313 consecutive coronary arteriograms) revealed 5 patients with SCAN, an incidence of 1.6%. SCAN involved the proximal and/or middle segments of the left anterior descending coronary artery in all patients. It is of particular note that the administration of nitroglycerin noticeably accentuated the SCAN phenomenon in each of 3 patients to whom it was administered. Four of the 5 patients had left ventricular hypertrophy due to hypertrophic cardiomyopathy (2), aortic stenosis (1), and hypertension (1). All 5 patients with the SCAN phenomenon had anginal chest pains, and critical obstructive coronary atherosclerosis was observed in only 2 cases. The other 3 patients showed, otherwise normal coronary arteriograms. Thus, myocardial bridges appear to be angiographically manifest predominantly in patients with cardiac hypertrophy. Nitroglycerin, which accentuates SCAN, might be useful as a provocative test to enhance the angiographic recognition of this phenomenon. The possible role of myocardial bridges in the production of myocardial ischemia warrants further investigation.
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PMID:Myocardial bridges in man: clinical correlations and angiographic accentuation with nitroglycerin. 40 19

Nitroglycerin and the long-acting nitrates are widely used in all of the anginal syndromes and have proven effectiveness in relieving or preventing myocardial ischemia. Recent developments into nitrate mechanisms of action provide new insights as to the many anti-ischemic effects of these agents. Important concepts relating to coronary arterial endothelial function are germane to nitrate therapy. Endothelial-derived relaxing factor (EDRF) is presently believed to be nitric oxide (NO), which exerts vasodilatory and/or antiplatelet actions by increasing intracellular cyclic guanosine monophosphate as a result of activation of the enzyme guanylate cyclase. In the setting of coronary atherosclerosis, or even hyperlipidemia without histologic vascular disease, endothelial dysfunction may be present, promoting a vasoconstrictor/proplatelet aggregatory milieu. Nitroglycerin and the organic nitrates are NO donors; NO is the final product of nitrate metabolism, and in the vascular smooth muscle NO induces relaxation, resulting in vasodilation of arteries and veins. In the presence of inadequate EDRF production and/or release, it appears that nitroglycerin may partially replenish EDRF-like activity. Nitrates have long been known to have major peripheral circulatory actions resulting in a marked decrease in cardiac work. Venodilation and arterial relaxation result in a decrease in intracardiac chamber size and pressures, with a resultant decrease in myocardial oxygen consumption. In addition, a variety of direct coronary circulatory actions of the nitrates have been documented. These include not only epicardial coronary artery dilation, but the prevention of coronary vasoconstriction, enhanced collateral flow, and coronary stenosis enlargement. Recent work suggests that the nitrates may also act by preventing distal coronary artery or collateral vasoconstriction, which can reduce blood flow downstream from a total coronary obstruction. Thus, there are many anti-ischemic mechanisms of action by which nitroglycerin and the organic nitrates may be beneficial in both acute and chronic ischemic heart disease syndromes. The unique salutory effects of the nitrates in subjects with left ventricular dysfunction or congestive heart failure make these drugs particularly attractive for patients with abnormal systolic function and intermittent myocardial ischemia. Finally, the emergent role of intravenous nitroglycerin in acute myocardial infarction offers new prospects that nitrate therapy may prove to be beneficial in acute myocardial infarction as well as postmyocardial infarction for the reduction of left ventricular remodeling.
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PMID:Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. 152 24

Nitroglycerin has dependable, short-lived veno- and arterial vasodilatory effects ameliorating ischemia through both preload reduction and coronary vasodilation. Nitroglycerin should be used prior to left ventriculography in patients with elevated left ventricular end-diastolic pressure. The arterial pressure waveform alteration of nitroglycerin can be explained on the basis of changes in arterial distensibility and reflected wave patterns and may vary considerably among individuals with different degrees of atherosclerosis.
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PMID:Interpretation of cardiac pathophysiology from pressure waveform analysis: effects of nitroglycerin. 157 82

Strip preparations of human epicardial coronary arteries (free of atherosclerosis) relaxed in an endothelium-dependent fashion to substance P and Ca2+-ionophore A23187. Acetylcholine generally caused contraction in the same strips. Glyceryl trinitrate and isoproterenol induced relaxation irrespective of the presence or absence of endothelium. Nordihydroguaiaretic acid abolished the relaxation produced by substance P and A23187. Mepacrine only blocked substance P relaxation. Haemoglobin and methylene blue inhibited substance P and A23187 relaxations but also reduced the response to glyceryl trinitrate. These inhibitor experiments indicate that human coronary arteries are relaxed by the endothelium-derived relaxing factor.
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PMID:Endothelium-dependent relaxation of human epicardial coronary arteries: frequent lack of effect of acetylcholine. 243 15

To test the hypothesis that atherosclerosis impairs endothelium-dependent vascular relaxation, we examined the effect of the endothelium-dependent vasodilators acetylcholine and thrombin and the endothelium-independent vasodilator nitroglycerin on iliac arteries from normal cynomolgus monkeys and cynomolgus monkeys with diet-induced atherosclerosis. Rings of iliac artery were suspended in organ chambers at their optimal length for generating tension. After preconstriction with prostaglandin F2 alpha, cumulative concentration-response curves to acetylcholine, thrombin, and nitroglycerin were examined. The presence of endothelium was confirmed in each vessel by scanning electron microscopy. Atherosclerotic vessels showed morphologic evidence of moderate to severe atherosclerosis. Acetylcholine produced a maximal relaxation of 65 +/- 10% in the normal group and 27 +/- 10% in atherosclerotic vessels (P less than 0.05). Thrombin (10.0 U/ml) produced relaxation of 39 +/- 9% in the normal group and 13 +/- 7% in atherosclerotic iliac arteries (P less than 0.05). Nitroglycerin relaxed both normal and atherosclerotic blood vessels to an equal extent; maximal relaxation was 92 +/- 4% in normal vessels and 98 +/- 2% in atherosclerotic vessels. To determine if hypercholesterolemia alone produces an abnormality in endothelium-dependent relaxation, we performed two additional studies. First, because veins are exposed to hypercholesterolemia, but do not develop atherosclerosis, we studied relaxation responses to acetylcholine and thrombin in veins from normal monkeys and monkeys with diet-induced atherosclerosis. Veins from normal and atherosclerotic monkeys relaxed to a similar extent upon exposure to the endothelium-dependent vasodilators acetylcholine and thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates. 308 55

Accelerated coronary atherosclerosis is a major cause of graft failure after heart transplantation. Graft atherosclerosis is typically diffuse and difficult to detect even with coronary arteriography. Recently, acetylcholine was shown to dilate blood vessels by releasing a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). We have demonstrated paradoxical vasoconstriction induced by acetylcholine both early and late in the course of coronary atherosclerosis in patients, suggesting an association of endothelial dysfunction and atherosclerosis. In this report, we tested the hypothesis that coronary arteries of heart transplant patients can show endothelial dysfunction before or in the early stages of angiographically evident coronary atherosclerosis. Acetylcholine was infused into the left anterior descending artery of 13 heart transplant patients at 12 (n = 9) and 24 (n = 4) mo after transplantation. Vascular responses were evaluated by quantitative angiography. Among patients with angiographically smooth coronary arteries, relatively few (6/25) arterial segments had preserved vasodilator responses, while the majority failed to dilate (10/25) or paradoxically constricted (9/25). Angiographically irregular coronary arteries were present in three patients, in whom 8/10 segments showed marked paradoxical constriction and the remaining 2/10 failed to dilate. Only 1 of 13 patients retained appropriate dilation to acetylcholine in all segments. Nitroglycerin, which acts directly on vascular smooth muscle, dilated nearly all segments. No clinical features of the patients, including myocardial rejection appeared to correlate with the impaired functional response of vessels. Thus impaired response to acetylcholine is a common early finding in heart transplant patients and emphasizes the potential importance of endothelial dysfunction in the development of atherosclerosis.
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PMID:Responses of coronary arteries of cardiac transplant patients to acetylcholine. 312 75

Impaired endothelium-dependent vasomotion in response to flow-mediated, cholinergic, and cold pressor stimulation has been demonstrated in the presence of both atherosclerosis and cardiac risk factors. This study investigated the effects of different vasoactive stimuli on brachial artery vasomotion with respect to age and gender. Forty healthy subjects (20 men and 20 women), ages 23 to 52 years, were studied. Using 7.5 MHz ultrasound, brachial artery diameter and Doppler flow velocity at baseline, following 5 min of ipsilateral blood pressure cuff occlusion (flow-mediated), during contralateral hand immersion in ice (cold pressor) and after sublingual nitroglycerin administration, were measured in older subjects (> 40 yrs) and younger subjects (< 40 yrs). Among normal subjects, % diameter change in response to the flow-mediated stimulus was less in older men than in younger men (6.8 +/- 3.2% vs. 11.5 +/- 7.4%, p < 0.05); older and younger women had comparable responses (10.0 +/- 5.3% vs. 11.6 +/- 4.3%, p = NS). With cold pressor, normal older men and older women vasoconstricted (-1.2 +/- 0.9%, -2.2 +/- 4.7%) compared with younger subjects who vasodilated (1.4 +/- 2.5%, 0.6 +/- 2.3%, p < 0.02). The cold pressor test elicited comparable responses among older normal subjects. Nitroglycerin, a non-endothelium-mediated stimulus, induced significant vasodilatation in all the groups. In conclusion, endothelium-mediated responses in subjects of varying age and gender are stimulus-dependent. Flow-mediated vasodilatation could not differentiate older premenopausal women from younger women; cold pressor stimulus could.
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PMID:The effects of age and gender on brachial artery endothelium-dependent vasoactivity are stimulus-dependent. 758 66

Although the inferior epigastric artery has been used as an alternative arterial graft for coronary artery bypass grafting, little is known about the contractile and relaxation characteristics of this artery. This study was designed to compare the pharmacologic reactivity of the two arterial conduits--the inferior epigastric artery and the internal mammary artery. Forty-one inferior epigastric artery ring segments from eight patients undergoing coronary grafting and 62 internal mammary artery ring segments were set up in organ baths under physiologic pressure. The contractility was determined from the contraction induced by the depolarizing agent potassium and receptor-mediated vasoconstrictor agents, norepinephrine, U46619, and endothelin-1. Endothelium-dependent relaxation was induced by the calcium ionophore A23187, a non-receptor agonist for endothelium-derived relaxing factor, and acetylcholine, a receptor agonist for endothelium-derived relaxing factor. Glyceryl trinitrate was used to study endothelium-independent relaxation. The maximal response (either contraction or relaxation) and the effective concentration causing 50% of the maximal response for these two arteries were compared. There was no difference (p > 0.05) either in the maximal contraction force (5.30 +/- 0.87 versus 4.76 +/- 0.89 gm for potassium, 5.13 +/- 0.67 versus 4.47 +/- 1.15 gm for norepinephrine, 8.04 +/- 1.23 versus 6.23 +/- 0.99 gm for U46619, and 4.88 +/- 0.69 versus 5.57 +/- 0.93 for endothelin-1 (n = 6 to 10 for each vasoconstrictor) or in the maximal relaxation induced by glyceryl trinitrate (86.46% versus 92.98%, n = 6) or by acetylcholine (20.72% versus 45.51%, n = 5) between the inferior epigastric artery and internal mammary artery. The effective concentration causing half maximal response to all vasoconstrictors and vasodilators was similar between the two arteries (p > 0.05). However, A23187 induced significantly less relaxation in the inferior epigastric artery (38.42 +/- 15.49%, n = 6) than in the internal mammary artery (71.89 +/- 7.17%, n = 9, p < 0.05). We conclude that contractility, endothelium-independent relaxation, and receptor-mediated endothelium-dependent relaxation are similar in the inferior epigastric artery and the internal mammary artery. However, the endothelium of this arterial graft has less ability to respond to the non-receptor-mediated endothelium-derived relaxing factor stimulant. The influence of this difference on the prevalence of atherosclerosis and long-term patency rate in the inferior epigastric artery remains to be studied.
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PMID:Functional comparison between the human inferior epigastric artery and internal mammary artery. Similarities and differences. 781 88

Nitroglycerin and the long-acting nitrates have been used in cardiovascular medicine for >100 years. Nitrates are widely utilized for the various anginal syndromes and are also used in congestive heart failure and patients with left ventricular dysfunction. The potential mechanisms for relief of myocardial ischemia with nitrates are multiple. The nitrovasodilators are a related group of drugs that result in the formation of nitric oxide (NO) within vascular smooth muscle cells. NO stimulates the enzyme guanylate cyclase, which results in increases in cyclic guanosine monophosphate and vasodilation. In the presence of atherosclerosis, endothelial dysfunction is ubiquitous and associated with decreased NO availability, probably due to increased destruction of NO by free radical anions. Nitrovasodilators, including the nitrates, supply exogenous NO to the vascular wall and improve the vasodilator state. When nitrates are administered, endothelial-dependent stimuli cause relaxation rather than constriction in the setting of endothelial dysfunction. Nitrates also have antiplatelet effects, and recent evidence confirms that these drugs decrease platelet aggregation and thrombosis formation. This may play an important role in the therapy of acute unstable myocardial ischemia, including unstable angina and myocardial infarction. Nitrate hemodynamic effects have been long known. They are primarily modulated through a decrease in myocardial work that results from smaller cardiac chambers operating with lower systolic and diastolic pressures. These changes are caused by a redistribution of the circulating blood volume away from the heart to the venous capacitance system, with a fall in venous return to the heart. The afterload or arterial effects of nitrates are also useful in decreasing myocardial oxygen consumption. Considerable evidence confirms a variety of mechanisms whereby nitrates increase coronary blood flow, including epicardial coronary artery dilation, stenosis enlargement, enhanced collateral size and flow, improvement of endothelial dysfunction, and prevention or reversal of coronary artery vasoconstriction. These effects help increase nutrient coronary blood flow to zones of myocardial ischemia. Recent data with the nitroglycerin patch confirm that myocardial ischemia is decreased after nitrate administration. Nitroprusside, another nitrovasodilator, is a commonly used intravenous agent for lowering arterial pressure and left ventricular filling pressure. This drug is highly effective for the treatment of acute or severe hypertension and congestive heart failure. However, there are data suggesting that nitroprusside may be deleterious in the presence of acute myocardial ischemia, perhaps by shunting blood away from zones of jeopardized myocardial blood flow. Therefore, nitroprusside cannot be recommended to treat myocardial ischemia; intravenous nitroglycerin should be used in this context.
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PMID:Beneficial actions of nitrates in cardiovascular disease. 863 24

Endothelial dysfunction is thought to be an important early event in atherogenesis, related in part to reduced bioavailability of nitric oxide in the arterial wall. Endothelial function may be impaired in the presence of oxidised low density lipoprotein. The use of vitamin E as an anti-oxidant might enhance the bioavailability of nitric oxide in this situation. The effect of vitamin E 1000 IU/day on arterial endothelial physiology was studied in 20 asymptomatic older subjects, aged 45-70 years, who showed evidence of age-related endothelial dysfunction. Endothelial function was assessed non-invasively using brachial ultrasound and the primary outcome measure was flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperaemia. A double-blind, placebo-controlled, randomised crossover design was employed. After 3 weeks of stabilisation on a standard fat-reduced diet, subjects received vitamin E or placebo for 10 weeks in random order, separated by a washout period of 8 weeks. There were no significant changes in blood pressure, plasma lipid or lipoprotein concentrations. Plasma alpha-tocopherol increased from 50+/-3 (mean+/-S.E.M.) to 91+/-6 micromol/l (P < 0.001) with vitamin E ingestion. Total plasma F2alpha-isoprostanes, a measure of free radical-induced lipid peroxidation, were not altered by vitamin E ingestion (0.86+/-0.26 versus 0.82+/-0.25 nmol/l, P > 0.6). FMD was not significantly different between the placebo and vitamin E periods (2.7+/-0.6% versus 2.4+/-0.4%). Variation in FMD was not correlated with change in plasma alpha-tocopherol (r = - 0.03, P > 0.8). The study was powered to detect a minimum change in FMD of 2%. Glyceryl trinitrate endothelium-independent dilatation was not significantly changed with vitamin E (13.7+/-1.3% versus 13.6+/-1.4%,). These results exclude a major impact of medium-term supplementation with vitamin E on arterial endothelial function when age-related dysfunction is already present.
Atherosclerosis 1999 Mar
PMID:Vitamin E ingestion does not improve arterial endothelial dysfunction in older adults. 1020 95


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