Endothelial dysfunction in a man with disruptive mutation in oestrogen-receptor gene.
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Adult↗
Biomedical subjects
T M Chou
Publications and source records attributed to T M Chou.
Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta.
OBJECTIVES: To assess the effects of interaction of sex hormones, hypercholesterolemia (HC) and environmental tobacco smoke (ETS) exposure on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of atherogenesis. BACKGROUND: Animal and human studies indicate the presence of interactions between classic coronary artery disease risk factors and endothelium-dependent relaxation. Sex hormones have also been shown to influence release of endothelium-derived relaxing factor. METHODS: New Zealand White rabbits were randomized to receive either an HC diet (n = 8) or ETS exposure plus HC diet (n = 8). Eight rabbits receiving a normal diet, without exposure to ETS, served as the control group. The HC diet consisted of 3% soybean oil and 0.3% cholesterol by weight over 13 weeks. The source of ETS was sidestream smoke of 4 cigarettes/15 min, 6 h/day, 5 days/week over 10 weeks in a smoking chamber. Rabbits were killed, and fresh aortic rings were harvested and maintained in oxygenated Krebs solution in an organ bath at 37 degrees C. Rings were precontracted with norepinephrine and exposed to acetylcholine in increasing doses, and isometric tension was recorded. Rings were also exposed to physiologic concentrations (1 nmol/liter) of either 17-beta-estradiol, testosterone or progesterone before pre-contraction with norepinephrine and relaxation with acetylcholine. Endothelium-independent relaxation was studied using nitroglycerin. The surface area of the ring covered by lipids was measured by Sudan IV staining. RESULTS: HC and ETS significantly reduced endothelium-dependent relaxation (p = 0.01 and p < 0.0005, respectively) and caused atherogenesis (p < 0.0005 and p = 0.047, respectively) but did not affect endothelium-independent relaxation. Incubation with estradiol and estradiol plus progesterone did not influence endothelium-dependent relaxation. Testosterone reduced endothelium-dependent relaxation (p = 0.049) and augmented the endothelial dysfunction associated with ETS exposure and HC (p = 0.03). CONCLUSIONS: Both HC and ETS are atherogenic and impair endothelial function but do not affect endothelium-independent relaxation. Physiologic levels of estradiol and estradiol plus progesterone do not affect endothelium-dependent relaxation. Physiologic levels of testosterone impair relaxation and augment the endothelial dysfunction associated with ETS exposure and HC.
Animals↗
Fetoscopic and open transumbilical fetal cardiac catheterization in sheep. Potential approaches for human fetal cardiac intervention.
BACKGROUND: Shortening the prenatal disease course of severe aortic and pulmonary stenoses by balloon valvuloplasty may diminish their postnatal expression. The purpose of this study in fetal sheep was to assess the feasibility of fetoscopic and open transumbilical fetal cardiac catheterization guided by fetal transesophageal echocardiography to provide alternative approaches for human fetal cardiac intervention. METHODS AND RESULTS: We studied a total of nine fetal sheep (95 to 103 days of gestation; term = 145 to 150 days) and performed transumbilical fetal cardiac catheterization by a minimally invasive fetoscopic (n = 6) or an open fetal surgical approach (n = 3). Monitored by fetal transesophageal echocardiography, with an 8F or 10F, 10-MHz intravascular ultrasound catheter we placed guidewires and interventional catheters via the umbilical arterial route into the fetal heart. In three of the fetuses, we created supravalvar pulmonary artery stenosis by open fetal cardiac surgery After fetal and maternal recovery, we exteriorized these fetuses and performed open transumbilical fetal cardiac catheterization with successful pulmonary arterial angioplasty in two. Three fetuses survived fetoscopic transumbilical catheterization for 1 or 2 days and died most likely of blood loss after sheath dislodgment (n = 1) or removal (n = 2). By securing the sheath insertion site with a suture, we prevented sheath dislodgment and minimized bleeding during sheath removal in three fetuses. These fetuses then survived fetoscopic transumbilical fetal cardiac catheterization for 1 to 2 weeks before being killed. CONCLUSIONS: This study in fetal sheep demonstrates that fetoscopic and open transumbilical fetal cardiac catheterization are feasible and, guided by fetal transesophageal echocardiography, provide potential alternative approaches for human fetal cardiac intervention.
Angioplasty, Balloon↗
Use of intravascular ultrasound in evaluating repeated balloon rupture during coronary stenting.
Balloon rupture during coronary angioplasty is a well-recognized complication of PTCA. Coronary angiography commonly fails to elicit the cause of balloon perforation. We present a case with multiple balloon rupture during additional high-pressure inflations of a Palmaz-Schatz stent where intravascular ultrasound was useful in revealing a calcified lesion protruding through the struts of the stent.
Aged↗
Sex hormones and vascular reactivity.
It is increasingly recognized that sex steroids have, among many other effects, the ability to cause vasodilation. The vasodilatory effects of estradiol have been the best documented and described. At low concentrations, estradiol has the ability to improve impaired endothelium dependent (nitric oxide mediated) relaxation in estrogen deficient subjects. At high concentrations, estradiol causes vasodilation principally by endothelium independent mechanisms, in a gender independent fashion, which appear to involve a number of pathways such as ATP-dependent K+ channels. Testosterone also has ability, at higher doses, to cause vasodilation of the coronary circulation, in a gender independent fashion. The mechanisms of sex steroid-induced vasodilation are reviewed in this article.
Animals↗
Frequency, duration, magnitude, and consequences of myocardial ischemia during intracoronary ultrasonography.
To determine the frequency, duration, magnitude, and possible adverse effects of ischemia during intracoronary ultrasonography, real-time standard 12-lead electrocardiograms were recorded before, during, and after ultrasonography. Ischemia was defined as new-onset ST segment deviation of > or = 1 mm in one or more leads, measured at J + 80 msec. The magnitude of ischemia was expressed as the sum of absolute ST segment deviations across 12 leads. Eighteen (67%) of 27 patients had ischemia during intracoronary ultrasonography. The electrocardiogram resembled the characteristic pattern observed with occlusion of the vessel under study, involving ST segment elevation in contiguous leads in 89% of patients. A higher proportion of women (88%) had ischemia than men (58%), and women had smaller arterial lumenal areas compared with men (6.3 vs 9.1 mm2; p < 0.05). Individuals with ischemia were smaller than those without ischemia (body surface area = 1.99 vs 1.79 m2; p = 0.01). The mean duration of ischemia was 4 minutes and the mean 12-lead ST segment deviation score was 8.5 mm (maximum 20.5 mm). No patient with ischemia during ultrasonography had complications. Ischemia is common during intracoronary ultrasonography, particularly in women and individuals with smaller vessels; however, no adverse outcomes occur as a result.
Aged↗
Effects of second-hand smoke and gender on infarct size of young rats exposed in utero and in the neonatal to adolescent period.
OBJECTIVES: We sought to assess the effects of second-hand smoke (SHS) and gender on infarct size in young rats exposed in utero or in the neonatal to adolescent period, or both. BACKGROUND: We previously demonstrated that exposure to SHS increases infarct size in a rat model of ischemia and reperfusion, with a dose-response relation. These results are consistent with epidemiologic studies demonstrating that SHS increases risk of death from heart disease. METHODS: Thirty-one pregnant female rats were randomly divided into two groups: those exposed to SHS and a control group (non-SHS). After 3 weeks, each rat had given birth to 10 to 12 rats. One hundred one neonatal rats were divided into four groups according to exposure to SHS in utero (SHSu) and randomized to SHS exposure in the neonatal to adolescent period (SHSna). After 12 weeks, all rats were subjected to 17 min of left coronary artery occlusion and 2 h of reperfusion. RESULTS: Birth mortality was higher in the SHSu group than in the non-SHSu group (11.9% vs. 2.8%, p < 0.001). Body weight of neonatal rats at 3 and 4 weeks in the two SHSu groups was lower than that of rats in the two non-SHSu groups (p < 0.001). Exposure to SHSna increased endothelin-1 levels in plasma (p = 0.001). In all 70 young rats who survived the neonatal period, infarct size (Infarct mass/Risk area x 100%) was greater in the SHSna groups than in the non-SHSna groups (p = 0.005) and in the male groups than in the female groups (p < 0.001). CONCLUSIONS: Exposure to SHS in the neonatal to adolescent period and male gender increased myocardial infarct size in a young rat model of ischemia and reperfusion. These results are consistent with epidemiologic studies demonstrating that SHS increases the health risk to neonates and adolescents.
Angiotensin II↗
Transesophageal echocardiography in rats using an intravascular ultrasound catheter.
In vivo assessment of cardiac structure and function in small animals is an important experimental goal, but currently available techniques have significant limitations. A commercially available intravascular ultrasound (IVUS) system was adapted to perform transesophageal echocardiography (TEE) in rats. Twelve Sprague-Dawley rats (270-370 g) were anesthetized with intraperitoneal pentobarbital sodium. A 4.3-Fr, 30-MHz or an 8-Fr, 20-MHz IVUS catheter was inserted into the esophagus to obtain long-axis views of the aortic arch, short-axis views of the ascending aorta, and long-axis views of the pulmonary artery. A preshaped, 8-Fr, 20-MHz catheter was used to obtain short-axis images of the left ventricle (LV) at the midpapillary muscle level, which were used to measure LV diastolic and systolic dimensions (diameters) and to calculate LV mass and fractional shortening. Measurements by TEE were compared with those obtained by transthoracic echocardiography in 6 of 12 rats. Postmortem, the LV was weighed to determine actual LV mass. The correlation coefficients between TEE- and transthoracic echocardiography-calculated LV mass and actual LV mass were 0.94 and 0.88, respectively, and had a good agreement with actual LV mass. Inter- and intraobserver variability of TEE measurements was <10%. IVUS instrumentation may offer an alternative technique for the accurate, serial assessment of LV dimensions, mass, and systolic function and a means of imaging the great vessels in small laboratory animals.
Animals↗
Chronic dietary L-arginine prevents endothelial dysfunction secondary to environmental tobacco smoke in normocholesterolemic rabbits.
Our goal was to determine whether environmental tobacco smoke causes endothelial dysfunction in the absence of hypercholesterolemia and whether such an effect can be prevented by supplementation with L-arginine. Environmental tobacco smoke exposure is associated with an increase in coronary artery disease events and mortality. We have previously demonstrated that environmental tobacco smoke causes endothelial dysfunction and atherosclerosis in rabbits with diet-induced hypercholesterolemia and atherosclerosis and that chronic dietary L-arginine supplementation prevents this. The effects of L-arginine supplementation (2.25% solution ad libitum) and environmental tobacco smoke (smoking chambers for 10 weeks) were examined with a 2 x 2 design in 32 rabbits fed a normal diet. Acetylcholine, calcium ionophore A23187, and nitroglycerin-induced vasorelaxation were assessed in aortic rings precontracted with phenylephrine. Endothelial L-arginine levels were measured by chromatography. Chronic L-arginine supplementation increased serum (P < .001) and endothelial (P = .003) L-arginine levels. Environmental tobacco smoke reduced endothelium-dependent acetylcholine-induced relaxation, and L-arginine blocked this adverse effect (P = .04). Environmental tobacco smoke tended to increase phenylephrine-induced contraction (P = .06). Neither environmental tobacco smoke nor L-arginine influenced A23187-induced relaxation nor endothelium-independent nitroglycerin-induced relaxation. Endothelial dysfunction secondary to environmental tobacco smoke may occur in the absence of diet-induced hypercholesterolemia and atherosclerosis. Chronic dietary supplementation with a nitric oxide donor such as L-arginine offsets the endothelial dysfunction associated with environmental tobacco smoke in normocholesterolemic rabbits, possibly through substrate loading of the nitric oxide pathway.
Animals↗
Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo.
BACKGROUND: Although estrogens have been shown to be vasoactive hormones, the vascular effects of testosterone are not well defined. Like estrogen, testosterone causes relaxation of isolated rabbit coronary arterial segments. We examined the vasodilator effects of testosterone in vivo in the coronary circulation and the potential mechanisms of its actions. METHODS AND RESULTS: Using simultaneous intravascular two-dimensional and Doppler ultrasound, we examined the effect of intracoronary testosterone in coronary conductance and resistance arteries in 10 anesthetized dogs (5 male, 5 female). We also assessed the contribution of NO, prostaglandins, ATP-sensitive K+ channels, and classic estrogen receptors to testosterone-induced vasodilation. Testosterone induced a significant increase in cross-sectional area, average coronary peak flow velocity, and calculated volumetric coronary blood flow at the 0.1 and 1 mumol/L concentrations. This effect was independent of sex. Pretreatment with N omega-nitro-L-arginine methyl ester to block NO synthesis decreased testosterone-induced increase in cross-sectional area, average coronary peak flow velocity, and coronary blood flow. Pretreatment with glybenclamide to assess the role of ATP-sensitive K+ channels did not influence testosterone-induced dilation in epicardial arteries but did attenuate its effect in the microcirculation. Pretreatment with indomethacin or the classic estrogen-receptor antagonist ICI 182,780 did not alter testosterone-induced changes. CONCLUSIONS: Short-term administration of testosterone induces a sex-independent vasodilation in coronary conductance and resistance arteries in vivo. Acute testosterone-induced coronary vasodilation of epicardial and resistance vessels is mediated in part by endothelium-derived NO. ATP-sensitive K+ channels appear to play a role in the vasodilatory effect of testosterone in resistance arteries.
Animals↗
Comparison of adenosine to dipyridamole in degree of coronary hyperemic response in heart transplant recipients.
Transplant coronary vasculopathy is associated with endothelial dysfunction. Microvascular function, assessed as coronary flow reserve, has been reported to be normal. We used intracoronary ultrasound technology to simultaneously assess conductance and resistance vessel function in response to standard dosages of the vasodilators adenosine and dipyridamole. Coronary hemodynamic changes were assessed in 11 heart transplant recipients, at a mean duration of 784 +/- 516 days after transplantation, using a 3.2Fr or 4.3Fr, 30-MHz ultrasound imaging catheter over a 0.014-inch Doppler guidewire. Measures of coronary average peak flow velocity (APV) and coronary cross-sectional area (CSA) were used to calculate volumetric flow during intravenous infusions of adenosine (140 micrograms/kg/min over 4 minutes) and dipyridamole (140 micrograms/kg/min over 4 minutes). Flow reserve was assessed as a ratio of maximal pharmacologically induced flow to steady baseline flow before infusion. Increase in APV (261.9% vs 194.6%, p = 0.005), lumenal CSA (+11.8% vs +4.2%, p = 0.01), peak volumetric blood flow (515.8 vs 317.2 ml/min, p = 0.007), and coronary flow reserve (2.93 +/- 0.74 vs 1.99 +/- 0.53, p < 0.001) were higher with adenosine than dipyridamole. Both agents caused similar decreases in systemic blood pressure and little change in heart rate. Adenosine appears to be a more potent coronary vasodilator than dipyridamole in denervated human transplant subjects. Adenosine has a vasodilator effect at the epicardial and microvascular levels, resulting in an overall increase in volumetric flow. Flow reserve in response to both endothelium-independent agents is decreased in comparison with previously established values, but the attenuation is greater with dipyridamole.
Adenosine↗
Impact of the operating physician on costs of percutaneous transluminal coronary angioplasty.
The hospital charts and billing records of 250 consecutive admissions for percutaneous transluminal coronary angioplasty (PTCA) at a university hospital were reviewed. Clinical characteristics, performing physician, angiographic features of the dilated lesion, procedural outcome, length of stay, and total and departmental hospital costs were recorded for each patient. We identified several independent predictors of hospital cost, including the physician ($4,400 increase from highest- to lowest-cost physician, p=0.004), age ($790 increase per 10-year increase in age, p=0.002), urgency of the procedure ($4,100 increase for urgent vs elective, p < 0.001), and combined angiography and PTCA ($850 increase vs separate angiography, p=0.04). Independent predictors of catheterization laboratory cost included the physician ($1,280 increase from highest- to lowest-cost physician, p=0.03), American College of Cardiology/American Heart Association lesion type B2 or C ($320 increase, p=0.03), and combined angiography and PTCA ($430 increase, p=0.003). Expensive operators used more catheterization laboratory resources than inexpensive operators; however, there are no significant differences in success rate or need for emergent bypass surgery between physicians. PTCA cost is determined by both patient characteristics and the performing physician. The increase in cost due to the physician was not explained by patient variables, lesions characteristics, success rate, or complications.
Angioplasty, Balloon, Coronary↗
Coronary vasodilation induced by angiotensin-converting enzyme inhibition in vivo: differential contribution of nitric oxide and bradykinin in conductance and resistance arteries.
BACKGROUND: We studied in coronary conductance and resistance arteries the coronary vasodilator effects of the angiotensin-converting enzyme inhibitor ramiprilat and the contribution of nitric oxide, bradykinin, and prostaglandins to this vasodilation. METHODS AND RESEARCH: In seven anesthetized dogs, a Doppler guidewire was placed in the circumflex coronary artery to measure coronary flow velocity, and an ultrasound imaging catheter was introduced over the Doppler wire to measure coronary cross-sectional area. Drugs were infused directly into the left main coronary artery to minimize systemic effects. Ramiprilat increased both epicardial cross-sectional area and coronary blood flow velocity, resulting in an increase in absolute coronary blood flow. Pretreatment with N omega-nitro-L-arginine methyl ester (100 micromol/L intracoronary) to block nitric oxide synthase attenuated ramiprilat-induced increase in epicardial coronary cross-sectional area (P<.05) but not in coronary flow velocity or coronary blood flow. In contrast, pretreatment with the selective bradykinin antagonist HOE 140 (10 micromol/L) attenuated ramiprilat-induced increase in flow velocity (P<.025) and coronary blood flow (P<.05) but not epicardial coronary cross-sectional area. Pretreatment with indomethacin (5 mg/kg body wt IV) did not alter ramiprilat-induced increase in epicardial cross-sectional area, nor did it significantly influence coronary blood flow. CONCLUSIONS: Other than decreasing angiotensin II production, acute ramiprilat-induced vasodilation in canine coronary conductance arteries is mediated in part by nitric oxide. Ramiprilat-induced vasodilation in resistance arteries is in part mediated by the action of bradykinin.
Angiotensin-Converting Enzyme Inhibitors↗
Experimental fetal transesophageal and intracardiac echocardiography utilizing intravascular ultrasound technology.
Fetal transesophageal and intracardiac echocardiography by utilizing ultrasound technology permits accurate definition of cardiac anatomy in fetal sheep. Because fetal transesophageal echocardiography is less invasive than intracardiac echocardiography, it has the potential to serve as a monitoring tool for currently developed open and fetoscopic fetal cardiac interventions.
Animals↗
Transesophageal echocardiography in fetal sheep. A monitoring tool for open and fetoscopic cardiac procedures.
BACKGROUND: Cardiac procedures in exteriorized fetuses or assisted by fetoscopy require monitoring capabilities not attended by conventional maternal transabdominal echocardiography. METHODS: We, therefore, assessed the potential of fetal transesophageal echocardiography (TEE) utilizing an intravascular ultrasound catheter (IVUC) for fetal cardiac monitoring. We inserted a 10-F-10-MHz IVUC into the esophagus in 12 exteriorized fetal sheep and by a fetoscopic approach in 4 fetal sheep. Cardiac events were observed. Heart rate, cardiac rhythm, patency of the foramen ovale and ductus arteriosus, and the width of the branch pulmonary arteries could be assessed in all fetuses. Ventricular contractility could be assessed only in fetuses weighing less than 2.5 kg. Larger fetuses did not allow adequate imaging of the apical portion of the ventricles because of limited tissue penetration of the IVUC. Fetal TEE permitted placing small guide wires in the cardiac atria and left ventricle. Short-lived premature beats following intracardiac manipulations of these wires could be observed by fetal TEE in all cases. RESULTS: At autopsy, no complications from IVUC insertion were observed in the exteriorized fetuses. Fetoscopic placement of the IVUC resulted in minor perioral skin erosion in two nonexteriorized fetuses. CONCLUSIONS: In conclusion, fetal TEE can be achieved with minor fetal injury and may provide useful information during open and fetoscopic cardiac procedures. Further improvements in IVUC design will permit the application of this technique to monitor human fetal cardiac procedures.
Animals↗
Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: correlation with high density lipoproteins.
OBJECTIVES: This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultrasound imaging. BACKGROUND: Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis. METHODS: Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque. RESULTS: Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [+/- SD] 0.25 +/- 0.16) than in the left main (0.11 +/- 0.16, p < 0.001) and iliac arteries (0.02 +/- 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index > or = 0.42 (left anterior descending artery) and > or = 0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery. CONCLUSIONS: In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease.
Adult↗
Occlusal vertical dimension in prosthodontics.
Occlusal vertical dimension is important in all aspects of prosthodontics. Unfortunately, there is no scientific method of determining the correct occlusal vertical dimension. The amount of interocclusal rest space (IRS) is a rough guide since muscle tone, which determines the space, is variable. IRS varies greatly from one patient to the next. It will automatically be correct when the occlusal vertical dimension is correct. IRS should not be interfered with regardless of its size. Many techniques have been used for determining occlusal vertical dimension in dentulous and edentulous patients. Regardless of the technique, the occlusal vertical dimension must be determined carefully by the dentist for a successful prosthesis.
Biometry↗
Role of echocardiography in primary care medicine. Controversies in hypertension, atrial fibrillation, stroke, and endocarditis.
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Atrial Fibrillation↗