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Oxypurinol improves coronary and peripheral endothelial function in patients with coronary artery disease.

Coronary endothelial dysfunction is a powerful prognostic marker in patients with coronary artery disease (CAD) that is centrally related to oxidative inhibition of nitric oxide (NO)-dependent vascular cell signaling. Xanthine oxidase (XO), which both binds to and is expressed by endothelial cells, generates superoxide and hydrogen peroxide upon oxidation of purines. Whether inhibition of xanthine oxidase activity results in improved coronary vasomotor function in patients with CAD, however, remains unknown. We assessed coronary and peripheral (brachial artery) endothelial function in 18 patients (pts; 65+/-8 years, 86% male) with angiographically documented CAD, preserved left ventricular function, and non-elevated uric acid levels (233+/-10 microM). Patients received incremental doses of intracoronary acetylcholine (ACh; 10(-7) to 10(-5) microM), and minimal lumen diameter (MLD) and coronary blood flow (CBF) were assessed before and after intravenous administration of oxypurinol (200 mg). Oxypurinol inhibited plasma XO activity 63% (0.051+/- 0.001 vs 0.019+/- 0.005 microU/mg protein; p<0.01). In pts who displayed endothelial dysfunction as evidenced by coronary vasoconstriction in response to ACh (n=13), oxypurinol markedly attenuated ACh-induced vasoconstriction (-23+/- 4 vs -15+/- 4% at ACh 10(-5) microM, p<0.05) and significantly increased CBF (16+/-17 vs 62+/-18% at ACh 10(-5) microM, p<0.05), whereas in patients with preserved coronary endothelial function, oxypurinol had no effect on ACh-dependent changes in MLD (+2.8+/- 4.2 vs 5.2+/- 0.7%, p>0.05) or CBF (135+/-75 vs 154+/-61%, p>0.05). Flow-mediated dilation of the brachial artery, assessed in eight consecutive patients, increased from 5.1+/-1.5 before to 7.6+/-1.5% after oxypurinol administration (p < 0.05). Oxypurinol inhibition of XO improves coronary vascular endothelial dysfunction, a hallmark of patients with CAD. These observations reveal that XO-derived reactive oxygen species significantly contribute to impaired coronary NO bioavailability in CAD and that XO inhibition represents an additional treatment concept for inflammatory vascular diseases that deserves further investigation.

Aged↗

Assessing the relationship between dental disease and coronary heart disease in elderly U.S. veterans.

Several recent studies have shown a link between dental disease and coronary heart disease. The authors studied 320 U.S. veterans in a convenience sample to assess the relationship between oral health and systemic diseases among older people. They present cross-sectional data confirming that a statistically significant association exists between a diagnosis of coronary heart disease and certain oral health parameters, such as the number of missing teeth, plaque benzoyl-DL-arginine-naphthylamide test scores, salivary levels of Streptococcus sanguis and complaints of xerostomia. The oral parameters in these subjects were independent of and more strongly associated with coronary heart disease than were recognized risk factors, such as serum cholesterol levels, body mass index, diabetes and smoking status. However, because of the convenience sample studied, these findings cannot be generalized to other populations.

Aged↗

[Echocardiography and MIBI-SPECT scintigraphy during dobutamine infusion in the diagnosis of coronary disease].

BACKGROUND AND PURPOSE: Dobutamine, an adrenergic agonist, has been combined with echocardiography and scintigraphy with MIBI-SPECT to detect coronary artery disease. Our purpose has been to compare echocardiography and MIBI-SPECT scintigraphy during dobutamine infusion for diagnosing coronary artery disease. METHODS: Both tests and coronary angiography have been performed on 72 consecutive patients with chest pain and no previous history of coronary artery disease. Dobutamine had administered up to 40 micrograms/kg/min. Atropine was given when necessary. MIBI was injected at peak stress. Echocardiographic continuous monitoring and SPECT images were carried out. Positivity was defined as: 1) echocardiographic: wall motion abnormalities of new onset, and 2) scintigraphic: dobutamine-induced perfusion abnormalities. RESULTS: Coronary artery disease was demonstrated in 49 patients. Echocardiography was positive in 37 of them (sensitivity of 75%) and MIBI-SPECT in 43 (sensitivity of 88%; p = NS). Specificity was higher with echocardiography (22/23, 96%) than with scintigraphy (16/23, 69%, p = 0.02). Accuracy was 82% for both tests. More patients with multivessel disease were detected by scintigraphy (61% versus 35%; p = 0.09). Agreement between tests was as follows: 1) results: 77% (kappa = 0.53); 2) segments: 86% (kappa = 0.65), and 3) artery diseased: 90% (kappa = 0.84). CONCLUSIONS: Echocardiography and MIBI-SPECT in combination with doubtamine are useful techniques to detect coronary artery disease. Diagnostic accuracy is similar with both tests.

Adrenergic beta-Agonists↗

Nitrous oxide added to halothane reduces coronary flow and myocardial oxygen consumption in patients with coronary disease.

The haemodynamic and myocardial metabolic effects of adding 50 per cent nitrous oxide to 0.5 per cent halothane were studied in 13 patients, before the surgical incision for coronary artery vein grafts. Cardiac output and coronary sinus blood flow were determined by thermodilution, along with haemodynamic measurements. Measurements 15 minutes after addition of nitrous oxide revealed a significant decrease in heart rate, arterial pressure, cardiac index, coronary sinus blood flow and myocardial oxygen consumption. There was a significant increase in coronary sinus lactate content, and a significant decrease, from 27 to 11 per cent, in myocardial lactate extraction. We conclude that these circulatory changes were likely to be due to a depression of ventricular function by the nitrous oxide. The myocardia of these patients with severe coronary disease were becoming globally ischaemic while they were receiving 50 per cent oxygen, in the presence of hypotension. Nitrous oxide should be turned off when hypotension occurs in coronary patients.

Coronary Artery Bypass↗

Contrast enhancement of thallium-201 myocardial scintigrams: improved sensitivity with diminished specificity in coronary disease detection.

Thallium-201 myocardial scintigraphy (TMS) has become an increasingly popular noninvasive technique with a high diagnostic specificity, but a somewhat lower sensitivity for coronary disease (CAD) detection. Many centers now routinely employ computer techniques to contrast enhance scintigrams, but the resulting changes in sensitivity and specificity have not been carefully evaluated. In the present study, three observers with different levels of experience blindly interpreted both unprocessed and enhanced exercise TMS from 40 patients with CAD and from 15 without significant obstructions. The sensitivity for CAD achieved by each observer was higher with the enhanced scintigrams (increase from an average of 80% to 93%), but there was concomitant loss of specificity (from 93% to 73%). Similarly, significant changes were present in the sensitivity and specificity with which ischemic regions were diagnosed. In addition, contrast enhancement facilitated interpretation of TMS studies, particularly in making comparisons between exercise scintigrams and subsequent rest or redistribution images. Contrast enhancement affected the interpretations of the inexperienced observer most significantly. We conclude that contrast enhancement improves TMS sensitivity but results in some loss of specificity. The variable effect of enhancement on observers with different levels of experience suggests that laboratories should critically evaluate their own results before routinely employing computer processing.

Computers↗

Coronary artery bypass surgery prior to resection of abdominal aortic aneurysm in patients with unstable coronary artery disease.

Coronary artery disease (CAD) is associated with abdominal aortic aneurysm in greater than 60% of cases. CAD continues to affect postoperative complication rates. Half of the deaths that follow resection of abdominal aortic aneurysms are due to perioperative myocardial infarctions. On evaluation for surgical resection of an abdominal aortic aneurysm, six patients were found to have significant CAD. Each underwent coronary artery bypass surgery prior to elective resection of the aneurysm. No deaths or myocardial infarctions occurred following any of the procedures. We restrict our indications for coronary angiography to the evaluation of patients with unstable angina (pain at rest or after minimal exertion) in whom noninvasive studies reveal evidence of CAD, and for patients who are unresponsive to medical management.

Aged↗

Lycopene, tomatoes, and the prevention of coronary heart disease.

Coronary heart disease (CHD) is one of the primary causes of death in the Western world. The emphasis so far has been on the relationship between serum cholesterol levels and the risk of CHD. More recently, oxidative stress induced by reactive oxygen species (ROS) is also considered to play an important part in the etiology of this disease. Oxidation of the circulating low-density lipoprotein (LDL(ox)) is thought to play a key role in the pathogenesis of atherosclerosis and CHD. According to this hypothesis, macrophages inside the arterial wall take up the LDL(ox) and initiate the process of plaque formation. Dietary antioxidants such as vitamin E and beta-carotene have been shown in in vitro studies to prevent the formation of LDL(ox) and their uptake by microphages. In a recent study, healthy human subjects ingesting lycopene, a carotenoid antioxidant, in the form of tomato juice, tomato sauce, and oleoresin soft gel capsules for 1 week had significantly lower levels of LDL(ox) compared with controls. The antioxidant effects of lycopene have also been shown in four other human trials, including one where lycopene consumption reduced the levels of breath pentane. However, in one recent study, dietary supplementation with beta-carotene but not with lycopene was shown to inhibit LDL oxidation. The sources of lycopene used in most of these studies were either tomato products or lycopene extracted from tomatoes containing other carotenoids in various proportions. Therefore, it is not possible to attribute the effects solely to lycopene. Mechanisms other than the antioxidant properties of lycopene have also been shown to reduce the risk of CHD. Lycopene was shown to inhibit the activity of an essential enzyme involved in cholesterol synthesis in an in vitro and a small clinical study suggesting a hypocholesterolemic effect. Other possible mechanisms include enhanced LDL degradation, LDL particle size and composition, plaque rupture, and altered endothelial functions. Recent epidemiological studies have also shown an inverse relationship between tissue and serum levels of lycopene and mortality from CHD, cerebrovascular disease, and myocardial infraction. However, the most impressive population-based evidence comes from a multicenter case-control study where subjects from 10 European countries were evaluated for relationship between antioxidant status and acute myocardial infarctions. After adjusting for a range of dietary variables, only lycopene levels but not beta-carotene were found to be protective. At present, the role of lycopene in the prevention of CHD is strongly suggestive. Although the antioxidant property of lycopene may be one of the principal mechanism for its effect, other mechanisms may also be responsible. Controlled clinical and dietary intervention studies using well-defined subject populations and disease end points must be undertaken in the future to provide definitive evidence for the role of lycopene in the prevention of CHD. Mechanistic studies must also be initiated to understand the mode of lycopene action.

Antioxidants↗

Expression of cytokine and adhesion molecule mRNA in atherectomy specimens from patients with coronary artery disease.

Coronary arteriosclerosis is an underlying condition in acute myocardial infarction (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP), and is also related to restenosis (RS) following coronary intervention. To investigate the pathogenesis of this condition, a quantitative reverse transcriptase polymerase chain reaction was used to determine relative levels of mRNA for interleukin (IL)-1beta, IL-6, IL-8, transforming growth factor beta (TGF-beta), intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell adhesion molecule (VCAM)-1 using directional coronary atherectomy (DCA) specimens. Eleven patients with AMI, 7 with UAP, 10 with SAP and 6 with RS following a previous coronary intervention underwent DCA. The mRNA intensity for each molecule was expressed by comparing it with that of beta-actin mRNA. The AMI and UAP patients showed high frequencies of mRNA for IL-1beta, IL-8, TGF-beta, and ICAM-1 together with strong intensities of expression, whereas SAP patients showed decreased mRNA expression for these molecules. Increased IL-6 mRNA expression was observed only in AMI samples. Specimens from RS patients revealed an accumulated expression of proinflammatory cytokines, except for IL-6, as well as of TGF-beta. The study suggests that variation in mRNA expression may reflect the pathophysiology of specific types of coronary artery disease, and remodeling following vascular injury.

Aged↗

[Coronary disease in patients after heart transplantation].

Coronary artery lesions are evaluated in a group of 43 patients surviving for more than 3 months after heart transplantation. An angiographic finding was obtained from 35 patients, autopsy findings were available in eight cases. Angiography demonstrated coronary artery lesions in 12 out of the 35 patients whereas autopsy findings were positive in five out of the eight post mortem examinations. Overall, lesions were found in 40% of patients at a mean follow-up interval of 3.5 years. While the finding of a coronary artery lesion was not related to the classic risk factors for atherosclerosis, an association to a previous cytomegalovirus or Epstein-Barr virus infection was demonstrated. The data suggest that infection caused by the two above viruses is an important factor in the development of vascular lesions in the heart transplant.

Adult↗

Role of computed tomography in risk assessment for coronary heart disease.

Coronary heart disease is the most common cause of death in Western countries, with a rising incidence in developing countries. It is part of the spectrum of cardiovascular diseases that have common end points of myocardial infarction, stroke and death. As these end points often occur suddenly and often in those with no known disease, identification of those people at high risk is important. Besides the known traditional risk factors, direct imaging of the calcified plaque as a marker for atherosclerotic disease has been extensively studied with electron beam computed tomography and now with multislice computed tomography. This review discusses the role of computed tomography in assessment of cardiovascular risk in both people with or without symptoms.

Calcinosis↗

Deletion polymorphism at the angiotensin-converting enzyme gene in Turkish patients with coronary artery disease.

Coronary artery disease (CAD) is a multifactorial disease in which genetic and environmental factors play an important role. These factors differ in each population. This study was carried out to determine whether there is an association between insertion/deletion (I/D) polymorphism and CAD in Turkish patients from Ankara. An I/D polymorphism in intron 16 of the gene coding for the angiotensin-converting enzyme (ACE) has been used to study the role of this gene in the aetiology of coronary atherosclerosis and hypertension. As there are no existing data for the Turkish population, we studied the I/D polymorphism of the ACE gene in 218 patients with CAD and 107 controls. Polymerase chain reaction (PCR) was used for genotyping the I and D alleles. The DD polymorphism of the ACE gene was significantly different between CAD subjects (0.733) and controls (0.612) (p=0.002). The observed heterozygosity was 29.3% and 43.9% and D allele frequency was 0.733 and 0.612, respectively. There was a significantly higher D allele (p=0.03) in 111 patients with myocardial infarction (MI) compared with controls. Furthermore, MI localization also gave a significance of p=0.002 for inferior MI but not for anterior MI (p=0.83). Forty-three hypertension patients had a D allele frequency of 0.767 which was significantly different from control (p=0.01). These data provide further evidence for the association of D allele and CAD in a Turkish population.

Adult↗