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A Lerman

Publications and source records attributed to A Lerman.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effect of basal epicardial tone on endothelium-independent coronary flow reserve measurement.

Increased basal epicardial tone may attenuate the coronary flow reserve (CFR) by causing vasodilatation of resistance vessels. We examined the effect of basal epicardial tone on the endothelium-independent CFR measurements in subjects with nonobstructive coronary disease. Patients underwent evaluation of endothelium-independent CFR using adenosine (18-36 microg) and endothelium-dependent CFR using acetylcholine (10(-6) M-10(-4) M), both administered intracoronary. CFR to adenosine, presented as the ratio of Doppler flow velocities post- and pre-adenosine, was measured at baseline and after intracoronary nitroglycerin (200 microg). Nitroglycerin increased the coronary artery diameter by 19.7 +/- 2.5%, and decreased the coronary vascular resistance from 3.0 +/- 0.2 mm Hg/ml/min to 1.8 +/- 0.1 mm Hg/ml/min (p < 0.0001). The response to adenosine at baseline and after nitroglycerin was similar (CFR ratio of 2.52 +/- 0.09 and 2.57 +/- 0.10, respectively, p = NS). The effect of nitroglycerin on the response to adenosine did not correlate with coronary endothelial function (r2 = 0.06, p = 0.13). The basal epicardial tone does not affect CFR measurements in patients with angina and nonobstructive coronary disease.

Acetylcholine↗
PubMed1998

Post-liver transplantation myocardial dysfunction.

Patients with end-stage liver disease usually show a hyperdynamic circulatory state. It has previously been reported that patients who develop myocardial depression in the early post-liver transplantation period are more prone to organ failure and death. We reviewed the records of 754 adult patients undergoing liver transplantation at our institution and identified 7 patients who initially showed hyperdynamic circulation, but then developed reversible dilated cardiomyopathy in the early posttransplantation period. All identifiable causes of cardiac dysfunction, such as myocardial ischemia, thyroid dysfunction, and electrolyte imbalances, were excluded. Left ventricular ejection fraction decreased from a preoperative median baseline of 60% to 20% (P = .02), with four-chamber dilatation on echocardiogram. All these patients required supportive care, including mechanical ventilation, afterload reduction, inotropic support, and monitoring in the intensive care unit. Cardiac function subsequently improved in all patients, with ejection fraction increasing to a median of 50%. All patients were discharged from the hospital. At a median follow-up of 15 months, there was no recurrence of heart failure. The increased peripheral resistance seen after successful liver transplantation may be an important causative factor.

Adolescent↗
PubMed1998

Insulin and IGF-I attenuate the coronary vasoconstrictor effects of endothelin-1 but not of sarafotoxin 6c.

OBJECTIVE: To examine the hypothesis that insulin and insulin-like growth factor I (IGF-I) attenuate endothelin-induced contraction of porcine coronary epicardial arteries in vitro. BACKGROUND: Endothelin-induced coronary vasoconstriction is mediated by two types of receptors, A (ETA) and B (ETB), resulting in calcium influx. Both insulin and IGF-I attenuate endothelin-induced calcium influx into porcine coronary artery smooth muscle. METHODS: Epicardial arteries harvested from juvenile pigs were contracted with cumulative concentrations of endothelin-1 (ETA- and ETB-receptor agonist; 10(-10)-10(-6) M) or of sarafotoxin-6c (ETB-receptor agonist; 10(-11)-10(-7) M). In additional experiments, endothelin-1 or sarafotoxin-6c were added after incubation with 10(-8) M regular insulin or IGF-I. These experiments were repeated in vessels without endothelium. Contraction for each vessel was calculated relative to the response to 60 mM KCl. RESULTS: The maximal contractions to endothelin-1 in vessels with and without endothelium were 158 +/- 8 and 200 +/- 21%, respectively (p < 0.05 at 10(-8.5)-10(-6.5) M). Both insulin (at 10(-7)-10(-6) M) and IGF-I (at 10(-6.5)-10(-6) M) attenuated the contraction to endothelin-1 in vessels with intact endothelium, as well as in vessels without endothelium (at 10(-7) and 10(-6) M for insulin and 10(-7.5)-10(-6) M for IGF-I). The maximal contractions to sarafotoxin-6c in vessels with and without endothelium were 54 +/- 13 and 84 +/- 7%, respectively (p < 0.05 at 10(-9), 10(-8.5) and 10(-7) M). Insulin and IGF-I did not affect the response to sarafotoxin-6c in vessels with and without endothelium. CONCLUSION: Insulin and IGF-I attenuated ETA-receptor-mediated coronary contraction through an endothelium-independent mechanism. The IGF axis may serve as an endogenous modulator of endothelin-mediated vasoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Endothelins.

Explore the source record for details and available documents.

Cardiovascular Diseases↗
PubMed1998

Experimental hypercholesterolemia induces ultrastructural changes in the internal elastic lamina of porcine coronary arteries.

The internal elastic lamina (IEL) serves as a barrier for cells and macromolecules migration between the intima and the media in the vascular wall. Several investigators have reported internal elastic lamina ultrastructural changes in elastic arteries with atherosclerosis. However, no quantitative and qualitative assessment of the internal elastic lamina architecture in muscular arteries such as the coronary circulation during early atherosclerosis have been performed yet. In this study, we therefore evaluated the ultrastructural morphological changes of the IEL in the coronary circulation of pigs fed with high cholesterol diet. Animals were sacrificed after being fed either a high cholesterol diet for 10-12 weeks (n = 5, 12 coronary segments) or a control diet (n = 4, 15 coronary segments). Coronary arteries were analyzed by transmission and scanning electron microscopy. In addition, computerized digital analysis of the images obtained by confocal scanning microscopy was performed for the quantitation of the morphologic changes in the internal elastic lamina. Confocal microscopy and scanning electron microscopy revealed an altered pattern characterized by large oval fenestration formation in the internal elastic lamina of hypercholesterolemic animals. Computerized morphometric analysis of confocal microscopy images demonstrated that compared to controls, the IEL of cholesterol-fed animals was characterized by an increase in the minor diameter of the fenestrae (2.16 +/- 0.04 microm versus 3.32 +/- 0.06 microm, P = 0.003) and a decrease in the fenestrae density (22333 +/- 1334/mm2 versus 17552 +/- 931/mm2, P = 0.015) of the internal elastic lamina. The percentage of the IEL area covered by the fenestrae correlated with the intimal thickness (r = 0.79, P = 0.004). This study demonstrates that experimental hypercholesterolemia is characterized by ultrastructural changes of the internal elastic lamina in the coronary circulation. This study suggests that the IEL may play an important role in the development of structural changes which characterize the early phase of coronary atherosclerosis.

Animals↗
PubMed1998

New insight into coronary endothelial dysfunction: role of endothelin.

The coronary endothelium plays a central role in the modulation of coronary vascular tone via the production and release of vasoactive mediators. A number of cardiovascular disease states are associated with coronary endothelial dysfunction, which results in an imbalance between vasoactive substances. Endothelin is a potent vasoconstrictor produced by the coronary endothelium and has been implicated in the pathogenesis of coronary endothelial dysfunction. This review examines the relationship between endothelin and coronary endothelial dysfunction as it occurs in a number of cardiovascular disease states and explores potential therapeutic options.

Animals↗
PubMed1998

Minimally invasive direct coronary artery bypass--a surgical approach for anomalous right coronary artery from left aortic sinus of Valsalva.

Anomalous origin of the right coronary artery from the left aortic sinus of Valsalva, although rare, has been associated with myocardial ischemia and sudden death. Methods of surgical correction include ostial reconstruction, excision and translocation of the vessel origin, and coronary artery bypass grafting. We describe a 39-year-old man with symptoms of myocardial ischemia and an anomalous right coronary artery in whom we performed the new, minimally invasive direct coronary artery bypass procedure with use of the right internal mammary artery.

Adult↗
PubMed1998

Adventitial vasa vasorum in balloon-injured coronary arteries: visualization and quantitation by a microscopic three-dimensional computed tomography technique.

OBJECTIVES: The objective of this study was to examine the quantitative response of the adventitial vasa vasorum to balloon-induced coronary injury. BACKGROUND: Recent attention has focused on the role of vasa vasorum in atherosclerotic and restenotic coronary artery disease. However, the three-dimensional anatomy of these complex vessels is largely unknown, especially after angioplasty injury. The purpose of this study was to visualize and quantitate three-dimensional spatial patterns of vasa vasorum in normal and balloon injured porcine coronary arteries. We also studied the spatial growth of vasa vasorum in regions of neointimal formation. A novel imaging technique, microscopic computed tomography, was used for these studies. METHODS: Four pigs were killed 28 d after coronary balloon injury, and four pigs with uninjured coronary arteries served as normal controls. The coronary arteries were injected with a low-viscosity, radiopaque liquid polymer compound. Normal and injured coronary segments were scanned using a microscopic computed tomography technique. Three-dimensional reconstructed maximum intensity projection and voxel gradient shading images were displayed at different angles and voxel threshold values, using image analysis software. For quantitation, seven to 10 cross-sectional images (40 normal and 32 balloon injured cross-sections) were captured from each specimen at a voxel size of 21 microm. RESULTS: Normal vasa vasorum originated from the coronary artery lumen, principally at large branch points. Two different types of vasa were found and classified as first-order or second-order according to location and direction. In balloon-injured coronary arteries, adventitial vasa vasorum density was increased (3.16+/-0.17/mm2 vs. 1.90+/-0.06/mm2, p = 0.0001; respectively), suggesting neovascularization by 28 d after vessel injury. Also, in these injured arteries, the vasa spatial distribution was disrupted compared with normal vessels, with proportionally more second-order vasa vasorum. The diameters of first-order and second-order vasa were smaller in normal compared with balloon-treated coronary arteries (p = 0.012 first-order; p < 0.001, second-order; respectively). The density of newly formed vasa vasorum was proportional to vessel stenosis (r = 0.81, p = 0.0001). Although the total number of vasa was increased after injury, the total vascular area comprised of vasa was significantly reduced in injured vessels compared with normals (3.83+/-0.20% to 5.42+/-0.56%, p = 0.0185). CONCLUSIONS: Adventitial neovascularization occurs after balloon injury. The number of new vessels is proportional to vessel stenosis. These findings may hold substantial implications for the therapy of vascular disease and restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1998

Acute endothelin-receptor inhibition does not attenuate acetylcholine-induced coronary vasoconstriction in experimental hypercholesterolemia.

Endothelin (ET) may mediate the enhanced coronary vasoconstriction associated with hypercholesterolemia. We hypothesized that short-term inhibition of ET receptors attenuates the coronary epicardial vasoconstrictor response to acetylcholine in experimental hypercholesterolemia. ET-1 (group I, n=5; 5 ng x kg[-1] x min[-1]) and acetylcholine (group III, n=7; 10[-6] to 10[-4] mol/L) were given by intracoronary infusion in pigs. ET-1 and acetylcholine were also infused with the specific ETA-receptor blocker FR-139317 (5 microg x kg[-1] x min[-1]; group II, n=6; group IV, n=6). Acetylcholine was also infused with the combined ET-receptor blocker, bosentan (0.5 mg/kg plus 1 mg x kg[-1] x h[-1], group V, n=5). The ETB-receptor agonist sarafotoxin 6c (5 ng x kg[-1] x min[-1]; n=4) was also infused. The percentage change in coronary artery diameter (%deltaCAD) to the infusions was measured at baseline and after 10 weeks of high-cholesterol diet in all animals. Sarafotoxin 6c mildly reduced %deltaCAD at baseline and 10 weeks (-10+/-2% and -12+/-3%, respectively). FR-139317 did not attenuate the epicardial vasoconstrictor response to ET-1 at baseline (%deltaCAD -18+/-8% for group I versus -12+/-6% for group II; P=NS) but did at 10 weeks (%deltaCAD -77+/-14% for group I versus -14+/-6% for group II; P<.05). FR-139317 did not affect the response to acetylcholine at baseline (%deltaCAD 5+/-2% for group III versus 7+/-3% for group IV, P=NS) or at 10 weeks (%deltaCAD -23+/-12% for group III versus -19+/-7% for group IV; P=NS). Bosentan did not affect the response to acetylcholine at baseline or 10 weeks. Short-term ET-receptor inhibition in experimental hypercholesterolemia attenuated the enhanced coronary epicardial vasoconstrictor effects of ET-1 but not acetylcholine-induced coronary epicardial vasoconstriction, suggesting that acetylcholine-induced coronary epicardial vasoconstriction may not be mediated by ET receptors.

Acetylcholine↗
PubMed1998

Insulin and insulin-like growth factor-I cause coronary vasorelaxation in vitro.

Insulin and insulin-like growth factor-I (IGF-I) may play a role in the modulation of coronary artery tone, yet there are few data regarding their vasoactive effects on the coronary vascular bed. We evaluated the vasorelaxation effects of insulin and IGF-I on porcine coronary epicardial vessels in vitro and elucidated possible mechanisms. Porcine epicardial arteries were contracted with 10(-7) mol/L endothelin-1 and relaxed with cumulative concentrations of either insulin or IGF-I (10(-12) to 10(-7) mol/L). The above experiments were repeated in vessels without endothelium. Vessels were also incubated with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(-4) mol/L) with and without 10(-3.5) mol/L L-arginine, the potassium channel blocker tetraethylammonium (TEA; 10(-2) mol/L), and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ; 10(-5.5) mol/L); vessels were then contracted with endothelin-1 and relaxed with insulin or IGF-I. Insulin and IGF-I were also added after contraction with 60 mmol/L KCl. Insulin and IGF-I caused a similar decrease in coronary epicardial tension after contraction with endothelin-1 (relaxation of 28+/-4% [n=7] and 25+/-3% [n=8] with insulin and IGF-I, respectively; P<0.0001 for both peptides). Removal of the endothelium did not affect these responses. Incubation with L-NMMA, but not ODQ, attenuated the vasorelaxation response to insulin and IGF in vessels without endothelium. L-Arginine did not reverse this effect of L-NMMA. KCl and TEA attenuated the vasorelaxation effect of both insulin and IGF-I. Thus, both insulin and IGF-I caused non-endothelium-dependent coronary vasorelaxation in vitro, probably through a mechanism involving the activation of potassium channels. These findings suggest that insulin and IGF-I participate in the regulation of coronary vasomotor tone.

Animals↗
PubMed1998

Ultrastructural changes of the internal elastic lamina in experimental hypercholesterolemic porcine coronary arteries.

The internal elastic lamina (IEL) serves as a barrier for cells and macromolecules between the intima and media in the vascular wall. We evaluated the morphological changes and quantitative assessments of the IEL architecture in the coronary circulation of pigs fed with a high cholesterol diet. Transmission electron microscopy (TEM) analysis of the IEL from hypercholesterolemic coronary arteries revealed fragmentation of the IEL associated with a decrease in the thickness. Confocal microscopy and scanning electron microscopy (SEM) revealed an altered pattern characterized by a large oval fenestration in the IEL of hypercholesterolemic vessels. Morphometric analysis of confocal microscopy images demonstrated that the IEL of cholesterol-fed animals were characterized by an increase in the minor diameter of the fenestrae (2.16+/-0.04 microm vs 3.32+/-0.06 microm, p=0.003) and a decrease in the fenestrae density (22,333+/-1,334/mm2 vs 17,552+/-931/mm2, p=0.015) compared to controls. The percentage of the IEL area covered by the fenestrae correlated with the intimal thickness (r=0.79, p=0.004). The immunoreactivity for matrix metalloproteinase-3 (MMP-3) increased in cholesterol-fed coronary arteries, predominantly in the neointima. This study demonstrates experimental hypercholesterolemia induced ultrastructural changes of the IEL in the coronary circulation. The IEL may play an important role in the development of structural changes which characterize the early phase of coronary atherosclerosis.

Animals↗
PubMed1998

Prevalence of coronary blood flow reserve abnormalities among patients with nonobstructive coronary artery disease and chest pain.

OBJECTIVE: To determine the prevalence of abnormalities in endothelium-dependent and endothelium-independent coronary flow reserve among patients with non-obstructive coronary artery disease and chest pain. MATERIAL AND METHODS: We studied endothelium-dependent (after infusion of 10(-6) M to 10(-4) M of acetylcholine) and endothelium-independent (after administration of 18 to 36 micrograms of adenosine) coronary flow reserve among patients with nonobstructive coronary artery disease and chest pain who were undergoing assessment at Mayo Clinic Rochester. Coronary blood flow was derived from coronary artery diameter assessed by quantitative angiography and Doppler flow velocities. RESULTS: The cohort consisted of 203 patients (158 female and 45 male patients), who ranged in age from 17 to 78 years (mean, 51). Most patients (92%) had at least one risk factor for atherosclerosis; a substantial proportion had undergone extensive cardiac and noncardiac evaluation. Whereas 41.5% of the patients had normal coronary flow reserve, 58.5% had an abnormal response: 11.3% an impaired response to adenosine (flow velocity ratio of 2.5 or less), 29.2% an impaired response to acetylcholine (flow reserve ratio of 1.5 or less), and 18% a combined abnormality. No correlation (r2 = 0.03) was noted between endothelium-dependent and endothelium-independent flow reserve. CONCLUSION: Most study patients with chest pain and nonobstructive coronary artery disease undergoing coronary vasomotor evaluation had risk factors for coronary artery disease and diverse abnormalities in endothelium-dependent or endothelium-independent coronary flow reserve (or both). These findings underscore the need for a comprehensive assessment.

Acetylcholine↗
PubMed1998

Predictors of smoking cessation after percutaneous coronary revascularization.

OBJECTIVE: To identify factors predictive of smoking cessation after successful percutaneous coronary revascularization. MATERIAL AND METHODS: We undertook a case-control study of the smoking status of all patients at Mayo Clinic Rochester from September 1979 through December 1995 who were smokers at the time of an index percutaneous coronary revascularization procedure in the non-peri-infarction setting (no myocardial infarction within 24 hours). Maximal duration of prospective follow-up was 16 years. Patients were classified into those who permanently quit smoking immediately after the procedure (N = 435; mean follow-up, 5.1 +/- 3.7 years) or those who continued to smoke at some time during follow-up (N = 734; mean follow-up, 5.3 +/- 3.7 years). Logistics regression models were formulated to determine independent predictors of smoking cessation. RESULTS: Predictors of continued smoking were greater prior cigarette consumption (odds ratio [OR] = 1.009 for each pack-year; 95% confidence interval [CI] = 1.004 to 1.014) and having one or more risk factors for coronary artery disease other than cigarette smoking (OR = 1.49; 95% CI = 1.15 to 1.93). Older age (OR = 0.98 for each additional year; 95% CI = 0.97 to 0.99) and unstable angina at time of initial assessment (OR = 0.69; 95% CI = 0.52 to 0.91) were associated with less likelihood of continued smoking. CONCLUSION: Younger patients with a worse risk profile and greater prior cigarette consumption were more likely than other patients to continue smoking after percutaneous coronary revascularization in the non-peri-infarction setting. Patients who had unstable angina were more likely to quit smoking than those who had stable angina. Despite the proven benefits of smoking cessation after percutaneous coronary revascularization, a substantial proportion of smokers (63%) continue to smoke; thus, smoking-cessation counseling should be addressed in this population.

Aged↗
PubMed1997

Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects.

BACKGROUND: Coronary endothelial dysfunction may occur in patients with minimally obstructive coronary artery disease and angina, and potentially may cause myocardial ischemia. METHODS AND RESULTS: Coronary endothelium-dependent vasodilation was examined in patients with angina and <50% coronary artery diameter (CAD) stenosis by selectively infusing acetylcholine (10(-6) mol/L to 10(-4) mol/L) into the left anterior descending coronary artery (LAD). Percent change in CAD (%deltaCAD) was measured by quantitative coronary angiography, and percent change in coronary blood flow (%deltaCBF) was calculated using intracoronary flow Doppler. Coronary endothelium-independent vasodilation was examined using intracoronary adenosine and nitroglycerin. 99mTc sestamibi was injected intravenously just prior to the infusion of the highest dose of acetylcholine. Patients were divided blindly into three groups: Perfusion defects in non-LAD territory (group 1, n=6), no perfusion defects (group 2, n=7), and perfusion defects in the LAD territory (group 3, n=7). All patients had intact endothelium-independent vasodilation. In group 1, perfusion defects outside the LAD territory reflected an increase in %deltaCAD and %deltaCBF by 24+/-5% and 241+/-46% in the LAD. In group 2, %deltaCAD decreased by 26+/-5%, but %deltaCBF increased by 54+/-17%. In group 3, perfusion defects were within the LAD territory, reflecting a decrease in %deltaCAD and %deltaCBF by 35+/-5% and 51+/-14%, respectively. CONCLUSIONS: This study demonstrates that coronary endothelial dysfunction in humans may be temporally associated with myocardial perfusion defects and supports a role for the coronary epicardial and microcirculation endothelium in regulating myocardial perfusion. Myocardial ischemia may occur in humans with impaired endothelium-dependent coronary flow reserve of the coronary epicardial and microcirculation.

Acetylcholine↗
PubMed1997

Enhanced endothelin-mediated coronary vasoconstriction and attenuated basal nitric oxide activity in experimental hypercholesterolemia.

BACKGROUND: Experimental hypercholesterolemia is associated with coronary vasomotor dysfunction. This study was designed to test the hypothesis that experimental hypercholesterolemia is characterized by altered coronary vasomotor responses to endothelin and inhibition of the endogenous NO pathway. METHODS AND RESULTS: Endothelin-1 (ET-1) at 5 ng x kg(-1) x min(-1) or N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase (NOS), at 50 microg x kg(-1) x min(-1) was infused into the left anterior descending coronary artery in pigs before and after 10 weeks of cholesterol diet. There was a significant increase in serum cholesterol. At 10 weeks, ET-1 resulted in an accentuated decrease in coronary blood flow (CBF) and coronary artery diameter (CAD) compared with baseline (-88+/-6% versus -45+/-9%, P<.05, and -77+/-14% versus -18+/-8%, P<.05, respectively) and an increase in coronary vascular resistance (CVR) (242+/-18% versus 110+/-17%, P<.05); ET receptor density and binding affinity in epicardial coronary arteries were unchanged. The effect of L-NMMA on CBF, CAD, and CVR was attenuated at 10 weeks (-7+/-8% versus -48+/-4%, -2+/-3% versus -17+/-5%, and 16+/-10% versus 125+/-32%; each P<.05). Immunohistochemistry staining for constitutive NOS revealed a decrease in immunoreactivity in the coronary arteries of hypercholesterolemic pigs. CONCLUSIONS: The present study demonstrates an enhanced coronary vasoconstrictive response to pathophysiological doses of endothelin and an attenuated response to the inhibition of endogenous NO activity, suggesting an alteration in coronary vascular reactivity in experimental hypercholesterolemia.

Acetylcholine↗
PubMed1997

Effect of smoking status on the long-term outcome after successful percutaneous coronary revascularization.

BACKGROUND: Cigarette smoking is known to be deleterious to patients with coronary artery disease, but the effect of smoking on the clinical outcome of percutaneous coronary revascularization is unknown. METHODS: Patients who had undergone successful percutaneous coronary revascularization at the Mayo Clinic between 1979 and 1995 were divided into nonsmokers (n=2009), former smokers (those who had stopped smoking before the procedure, n=2259), quitters (those who stopped smoking after the procedure, n=435), and persistent smokers (those who smoked before and after the procedure, n=734). RESULTS: The maximal follow-up was 16 years (mean [+/-SD], 4.5+/-3.4). The nonsmokers and former smokers had similar base-line characteristics and outcomes. The quitters and persistent smokers were younger than the nonsmokers and former smokers and had more favorable clinical and angiographic characteristics. In analyses adjusted for confounding base-line characteristics, the persistent smokers had a greater relative risk of death (1.76 [95 percent confidence interval, 1.37 to 2.26]) and of Q-wave infarction (2.08 [95 percent confidence interval, 1.16 to 3.72]) than the nonsmokers. The quitters and persistent smokers were less likely than the nonsmokers to undergo additional percutaneous coronary procedures (relative risk, 0.80 [95 percent confidence interval, 0.64 to 0.98] and 0.67 [95 percent confidence interval, 0.56 to 0.81], respectively) or coronary bypass surgery (relative risk, 0.72 [95 percent confidence interval, 0.54 to 0.95] and 0.68 [95 percent confidence interval, 0.54 to 0.86], respectively). The persistent smokers were also at greater risk for death than the quitters (relative risk, 1.44 [95 percent confidence interval, 1.02 to 2.11]). CONCLUSIONS: Patients who continued to smoke after successful percutaneous coronary revascularization were at greater risk for Q-wave infarction and death than nonsmokers. The cessation of smoking either before or after percutaneous revascularization was beneficial. Patients undergoing percutaneous revascularization should be encouraged to stop smoking.

Aged↗
PubMed1997

Mechanical pressure and stretch release endothelin-1 from human atherosclerotic coronary arteries in vivo.

BACKGROUND: Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with mitogenic properties. In vitro, vascular release of ET-1 is increased in response to mechanical stress. The goal of the present study was to examine whether ET-1 is released from human atherosclerotic coronary arteries in vivo in response to mechanical pressure and stretch and to characterize immunoreactivity for ET-1 and its precursor, big ET-1, within the atheromatous plaque. METHODS AND RESULTS: Circulating ET-1 levels were measured in 20 patients before and after coronary angioplasty for stable angina at three sampling sites: the femoral artery and the coronary artery segments proximal and distal to the lesion dilated. In addition, atheromatous tissue obtained from 20 patients undergoing directional coronary atherectomy for stable angina were analyzed for immunoreactivity for ET-1 and big ET-1. In patients undergoing angioplasty, ET-1 levels in the distal coronary artery increased after balloon dilatation (8.4 +/- 0.9 to 16.4 +/- 2 pg/mL, P < .05); proximal coronary artery and systemic ET-1 levels were unchanged. The degree of mechanical stress applied (product of duration and pressure of balloon inflation) correlated with the change in distal coronary artery ET-1 levels (r = .71, P < .01). Immunoreactivity for big ET-1 and ET-1 was ubiquitous in the extracellular space and the intracellular compartment (macrophages, myointimal cells, myofibroblasts, and endothelial cells) of human coronary atheromatous tissue. CONCLUSIONS: Big ET-1 and ET-1 immunoreactivity is ubiquitous within the intracellular and extracellular compartments of coronary atherosclerotic tissue. ET-1 is released from these sites in response to mechanical stress. These findings support a role for endothelins in the evolution and progression of coronary atherosclerosis in humans.

Aged↗