J. L. Mehta

Evaluation of venous and arterial conduit patency by 16-slice spiral computed tomography.

Background—Computed tomography has been shown to be useful in the evaluation of aortocoronary bypass grafts (CABG). This is the first prospective study to evaluate the accuracy of a new-generation scanner in the detection of patency and significant stenoses (>50% decrease in diameter) of venous and arterial grafts in patients with previous CABG. Methods and Results—In 96 patients (80 males, mean age 62 years) with previous CABG, a multislice computed tomography (MSCT) scan was performed (collimation 16×0.625 mm). Patients with atrial fibrillation, renal failure, severe respiratory disease, severe heart failure, heart rate >70 bpm despite therapy, or unstable angina were excluded. A total of 285 conduits implanted on the native coronary arteries at the time of CABG were evaluated. MSCT data were analyzed by 2 independent radiologists and compared with the results of conventional angiography. Three patients were excluded from analysis. All conduits were judged evaluable in 84 patients. Among these patients, MSCT correctly diagnosed 54 occluded grafts and 4 significant stenoses on the body of the grafts. Of the 17 significant anastomotic lesions, MSCT correctly diagnosed 15. For these 84 patients, diagnostic accuracy was 99%, sensitivity was 97%, and specificity was 100%. When all 93 patients were considered, the sensitivity of MSCT in diagnosing significant stenoses was 96%. Conclusions—MSCT with the new-generation scanner allows for accurate assessment of venous and arterial conduits in patients with previous CABG with a high degree of sensitivity and specificity. Exclusion criteria and radiation exposure remain limitations of the method.

Association of single nucleotide polymorphisms in the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction

Acute myocardial infarction (AMI) is a significant cause of mortality and morbidity. Substantial data support a plausible role for oxidised LDL (oxLDL) in the aetiology of this disease.1,2 The human OLR1 (or LOX 1) gene encodes the endothelium derived lectin-like oxidised low density lipoprotein (oxLDL) receptor, which is involved in the binding, internalisation, and proteolytic degradation of oxLDL, suggesting that it may play a significant role in atherogenesis.3 OLR1 is considered a good candidate for atherosclerosis and AMI since it is induced in vitro by inflammatory cytokines and in vivo by pro-atherogenic conditions like hypertension, hyperlipidaemia, and diabetes mellitus.4 Recently, upregulation of OLR1 has been shown in ischaemia reperfusion injury in the rat.5 OLR1 acts as a mediator of “endothelial dysfunction” favouring superoxide generation, inhibiting nitric oxide production, and enhancing endothelial adhesiveness for monocytes.6–8 It is noteworthy that the versatile activities of OLR1 also include the ability to bind not only oxLDL, but also aged red blood cells, apoptotic cells, and activated platelets.4 With this background, we sought to validate the hypothesis of OLR1 involvement in atherosclerosis and AMI by defining OLR1 genetic variation by an association study of intragenic SNPs. ### Study subjects The study included 150 individuals with AMI who were referred to the Centre of Atherosclerosis at the Medical School of the Tor Vergata University of Rome. All cases were clinically evaluated and all underwent coronary angiography and left ventriculography. The diagnosis of AMI was based on typical electrocardiographic changes and increased serum activities of at least two enzymes, such as creatine kinase, aspartate aminotransferase, and lactate dehydrogenase. The diagnosis was confirmed by the presence of wall motion abnormality on left ventriculography and attendant stenosis (>50%) in any of the major coronary arteries or in the left main coronary artery on coronary …

Protection of Myocytes From Hypoxia-Reoxygenation Injury by Nitric Oxide Is Mediated by Modulation of Transforming Growth Factor-β1

Background—Reoxygenation injury is a result of several complex events, including release of reactive oxygen species, protein kinase C (PKC) activation, and altered expression of transforming growth factor-&bgr;1 (TGF-&bgr;1). Nitric oxide (NO) generally protects tissues from reperfusion injury. Methods and Results—We examined the modulation of TGF-&bgr;1 expression and activity and PKC activation in cultured rat heart myocytes exposed to a brief period of hypoxia-reoxygenation (H-R) by NO donor 3-morpholino-sydnonimine (SIN-1). H-R resulted in an increased expression of total TGF-&bgr;1 (mRNA and protein) but a decrease in the release of active TGF-&bgr;1. Myocyte PKC-&agr; protein level was not altered by H-R, but its phosphorylation was augmented. Pretreatment of myocytes with SIN-1 diminished myocyte injury quantified as lactate dehydrogenase release. Simultaneously, release of active TGF-&bgr; 1 increased and total TGF-&bgr;1 expression decreased (all P <0.05 versus H-R alone). PKC-&agr; phosphorylation increased further in cells treated with SIN-1. The effects of SIN-1 were blocked by the NO scavenger phenyl-tetramethyl-imidazoline-oxyl-oxide as well as by the PKC inhibitor staurosporine. To examine if another NO donor would have a similar effect, cardiomyocytes were treated with nitroglycerin before H-R. With nitroglycerin treatment, similar to SIN-1 treatment, myocyte injury was diminished, TGF-&bgr; 1 release increased, and total TGF-&bgr; 1 expression decreased. Conclusions—These observations suggest modulation of TGF-&bgr; 1 expression as a novel mechanism of salutary effect of NO donors. PKC-&agr; activation may play an important role in the protective effect of NO against H-R injury.

Modulation of cardiovascular remodeling with statins: fact or fiction?

The concept of cardiac remodeling implies a complex mixture of myocardial ischemia, and increased wall stress that results in molecular, cellular and interstitial changes in the heart. Clinically, cardiac remodeling is manifested as a change in size, shape and function of the heart. Morphologically the key feature of remodeling is myocyte hypertrophy, myocyte loss from necrosis or apoptosis, as well as interstitial cell growth especially fibroblast proliferation leading to myocardial fibrosis. Cardiac remodeling is influenced by hemodynamic load, neurohumoral activation, and other factors that can further affect the remodeling process. Despite advances in the management of heart failure, morbidity and mortality still present major health care issues in these patients. Statins (HMG Coenzyme A reductase inhibitors) play a key role in the management of ischemic heart disease. Recent studies indicate that statins may modulate cardiac remodeling by affecting signals that cause fibroblast growth, and myocyte hypertrophy and loss. In this paper we review the mechanisms of cardiac remodeling and the mechanisms of potential beneficial effects of statins on cardiac remodeling.

Effect of stable fish oil on arterial thrombogenesis, platelet aggregation, and superoxide dismutase activity

We examined the influence of dietary stable fish oil on aortic thrombosis, platelet aggregation, and superoxide dismutase (SOD) activity in a rat model. Twenty-nine Sprague-Dawley rats were fed regular chow supplemented with stable fish oil preparation (for 1 or 3 weeks), and 37 rats fed regular chow served as controls. The abdominal cavity was opened, and the abdominal aorta isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was continuously recorded. In control rats, an occlusive platelet-fibrin-rich thrombus was formed in 21 +/- 3 min. Dietary fish oil in a time-dependent fashion delayed time to thrombus formation (24 +/- 2 min in rats fed fish oil for 1 week and 31 +/- 2 min in rats fed fish oil for 3 weeks), inhibited platelet aggregation (21 +/- 5% vs. 45 +/- 6%; p < 0.01) and increased SOD activity (p < 0.01). We conclude that dietary supplementation with stable fish oil delays formation of arterial thrombus, probably by reducing platelet aggregation and oxidative stress-associated arterial injury.

Role of genetics in prevention of coronary atherosclerosis

Atherosclerosis is currently regarded as a complex disorder, triggered by gene–gene and gene–environment interactions. Despite the difficulties of multifactorial disease genetic analysis, significant progress has been achieved in the search for atherosclerosis susceptibility genes. Here, we review these advances with regard to genome scan results and candidate gene analysis.

Trends in the Care of Patients With Acute Myocardial Infarction at a University-Affiliated Veterans Afffairs Medical Center:

Background: Acute cardiac care of the veterans at Veterans Administration (VA) hospitals has been thought of as poor in quality. We examined the use of life-saving, evidence-based medical therapy in patients admitted with acute myocardial infarction to the University of Arkansas for Medical Sciences-affiliated VA Medical Center in Little Rock and compared the use of this therapy with other hospitals in Arkansas and in the rest of the nation. Methods: Use of life-saving medical therapy in 117 patients admitted with acute myocardial infarction from January 2002 to December 2002 was compared with the National Registry of Myocardial Infarction database for the identical period. Results: Heparin/low-molecular-weight heparin and glycoprotein IIb/IIIa inhibitors were used in 88% and 66% of patients, respectively. Aspirin, β adrenergic-blocking agents, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) were used in 92%, 93%, 62%, and 79% of the patients, respectively. The use of these therapies was better than in similar patients in Arkansas (P < .001) and the United States as a whole (P < .01). Calcium-channel blockers were used in 16% of the patients. At a mean follow-up period of 1.5 years, use of β blockers and aspirin had decreased, whereas the use of statins and ACE inhibitors/ARBs was unchanged. Conclusion: This study shows that patients with acute myocardial infarction admitted to this university-affiliated VA Medical Center receive evidence-based life-saving medical therapy more often than in the rest Arkansas or in the entire United States. More important, patients at this federal institution continue to receive life-saving medical therapy during follow-up. Better use of evidence-based therapy may be related to affiliation of this VA Medical Center with a teaching institution where board certified cardiologists are involved in short- and long-term care of these patients.

Fish Oil — a Potential Therapy for Inflammatory Atherosclerosis

Inflammation plays an important role in both the initiation of atherosclerosis and the development of atherothrombotic events [1]. An anti-inflammatory effect of n3 fatty acids in fish oil was suggested by epidemiological studies which show that Greenland Eskimos, who consume large quantities of fish oils rich in long-chain n3 fatty acids, have a very low incidence not only of atherosclerosis and coronary artery disease but also of inflammatory and autoimmune disorders such as rheumatoid arthritis, psoriasis, asthma, inflammatory bowel disease, type I diabetes mellitus, thyrotoxicosis and multiple sclerosis [2].

Role of Infection in Atherosclerosis and Precipitation of Acute Cardiac Events

Atherosclerotic vascular disease is now widely considered to be associated with inflammation. The earliest lesion in atherosclerosis, the so-called “fatty streak”, is an inflammatory lesion consisting of monocyte-derived macrophages and T lymphocytes. As atherosclerosis proceeds, there is extensive infiltration of the blood vessels with T lymphocytes. The shoulder region of the rupture-prone plaque is characterized by extensive accumulation of inflammatory cells. These issues have been discussed in detail elsewhere in this book and in recent reviews [1-3].