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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2005.08.023 Byline: James M. Brophy (a)(b), Mohan N. Babapulle (a), Vania Costa (b), Stephane Rinfret (c) Abstract: After percutaneous coronary intervention (PCI), the antiplatelet drug clopidogrel is frequently used to prevent stent thrombosis. A concern has been raised that atorvastatin may competitively inhibit the metabolism of the prodrug clopidogrel to its active metabolites by the cytochrome P450 3A4 (CYP3A4) enzyme, thereby potentially negating its antiplatelet effect. The 30-day rates of adverse cardiovascular events (composite of death, myocardial infarction, 11 unstable angina, stroke or transient ischemic attack, and repeat revascularization procedures) in unselected 12 patients prescribed clopidogrel after PCI as a function of their exposure to CYP3A4 inhibitors has not been fully resolved. Author Affiliation: (a) Division of Cardiology, Royal Victoria Hospital/McGill University Health Center, Montreal, Quebec, Canada (b) Division of Clinical Epidemiology, Royal Victoria Hospital/McGill University Health Center, Montreal, Quebec, Canada (c) Department of Medicine, HA[acute accent]pital Notre Dame/Centre HA[acute accent]spitalier de l'Universite de Montreal, Montreal, Quebec, Canada Article History: Received 20 April 2005; Accepted 15 August 2005

We tested the hypothesis that myocardial ischemia-reperfusion (I/R)-induced apoptosis is attenuated in transgenic mice overexpressing cardiac [A.sub.1] adenosine receptors. Isolated hearts from transgenic (TG, n = 19) and wild-type (WT, n = 22) mice underwent 30 min of ischemia and 2 h of reperfusion, with evaluation of apoptosis, caspase 3 activity, function, and necrosis. I/R-induced apoptosis was attenuated in TG hearts. TG hearts had less If R-induced apoptotic nuclei (0.88 [+ or -] 0.10% vs. 4.22 [+ or -] 0.24% terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in WT, P < 0.05), less DNA fragmentation (3.30 [+ or -] 0.38-fold vs. 4.90 [+ or -] 0.39-fold over control in WT, P < 0.05), and less If R-induced caspase 3 activity (145 [+ or -] 25% over nonischemic control vs. 234 [+ or -] 31% in WT, P < 0.05). TG hearts also had improved recovery of function and less necrosis than WT hearts. In TG hearts pretreated with LY-294002 (3 [micro]M) to evaluate the role of phosphosinositol-3-kinase in acute signaling, there was no change in the functional protection or apoptotic response to UR. These data suggest that cardio-protection with transgenic overexpression of [A.sub.1] adenosine receptors involves attenuation of UR-induced apoptosis that does not involve acute signaling through phosphoinositol-3-kinase. cardioprotection; ischemia-reperfusion injury; transgenic mice; phosphoinositol-3-kinase

Cardiac gene expression profile and lipid accumulation in response to starvation. Am J Physiol Endocrinol Metab 46: E94-E102, 2002. First published March 5, 2002; 10.1152/ajpendo.00017.2002.--Starvation induces many biochemical and histological changes in the heart; however, the molecular events underlying these changes have not been fully elucidated. To explore the molecular response of the heart to starvation, microarray analysis was performed together with biochemical and histological investigations. Serum free fatty acids increased twofold in both 16- and 48-h-fasted mice, and cardiac triglyceride content increased threefold and sixfold in 16- and 48-h-fasted mice, respectively. Electron microscopy showed numerous lipid droplets in hearts of 48-h-fasted mice, whereas fewer numbers of droplets were seen in hearts from 16-h-fasted mice. Expression of 11,000 cardiac genes was screened by microarrays. More than 50 and 150 known genes were detected by differential expression analysis after 16- and 48-h-fasts, respectively. Genes for fatty acid oxidation and gluconeogenesis were increased, and genes for glycolysis were decreased. Many other genes for metabolism, signaling/cell cycle, cytoskeleton, and tissue antigens were affected by fasting. These data provide a broad perspective of the molecular events occurring physiologically in the heart in response to starvation. microarray analysis; differential expression; lipid droplet

Byline: Rajendra H. Mehta, Erik J. Stalhandske, Patricia A. McCargar, Thomas J. Ruane, Kim A. Eagle Abstract: Background The objective of this study was to assess the characteristics of patients with acute myocardial infarction transferred from community hospitals. The study was designed as a retrospective chart review, and the data source was the Cooperative Cardiovascular Project from Michigan. Methods and Results Included in the study were consecutive Medicare patients with acute myocardial infarction discharged from acute-care hospitals in Michigan between April 1, 1994, and July 31, 1995 (n = 7041): 2866 patients treated at community hospitals, 1241 transferred from community hospitals, 2731 admitted directly to tertiary hospitals, and 203 transferred from an outside emergency room to tertiary hospitals. The outcomes measured were patient characteristics, quality indicators, resource use, and 30-day mortality rates. Compared with patients not transferred, those transferred from community hospitals were younger, more frequently of the male sex, smokers, and were seen earlier after symptom onset. They had fewer cases of diabetes and lower Acute Physiology And Chronic Health Evaluation (APACHE II) scores and Medicare Mortality Prediction System (MMPS) values. Aspirin during hospitalization and at discharge, thrombolytic therapy, and reperfusion therapy were all used more frequently in transferred patients, whereas the other key discharge quality indicators were no different. Mortality rate at 30 days was lower for transferred patients (9.4% vs 25%, P < .0001) when compared with those not transferred. Conclusions Patients who are less ill, those who are seen early, and those who received thrombolytic therapy are more often transferred from community hospitals. On average, patients with greater comorbidity rates are treated at community hospitals and not transferred. Predicted and observed mortality rates were lower for the transferred group. Higher comorbidity rate in patients treated at community hospitals appears to be the major determinant of the observed higher mortality rates in these patients. (Am Heart J 1999;138:688-95.) Author Affiliation: Plymouth and Ann Arbor, Mich From the Center For Health Outcomes and Evaluation and the Heart Care Outcomes Assessment Team, Division of Cardiology, University of Michigan Article History: Received 24 July 1998; Accepted 3 February 1999 Article Note: (footnote) [star] Reprint requests: Kim A. Eagle, MD, FACC, B1F245 University Hospital, 1500 E Medical Center Dr, Ann Arbor, MI-48109. E-mail: keagle@umich.edu , [star][star] 0002-8703/99/$8.00 + 0 4/1/97846

Byline: Bernhard R. Winkelmann, Andreas P. Russ, Markus Nauck, Barbel Klein, Bernhard O. Bohm, Volker Maier, Rainer Zotz, Georg Matheis, Andreas Wolf, Heinrich Wieland, Werner GroA, David J. Galton, Winfried Marz Abstract: Background Genes encoding components of the renin-angiotensin system have been associated with elevated blood pressure (BP) and an increased risk of coronary artery disease. To explore the role of the angiotensinogen (AGT) gene in coronary atherosclerosis and thrombosis, we studied the effect of the AGT M235T gene variant on plasma AGT levels and BP in patients with coronary artery disease and in the subgroup of survivors of myocardial infarction as compared with angiographically defined control subjects. Methods and Results This was a case-control study of 301 white male subjects examined at Frankfurt University medical center. Plasma AGT levels increased stepwise according to the number of T235 alleles present (no T235 allele, 14.8 [+ or -] 3.9 nmol/L; 1 allele, 15.7 [+ or -] 5.1 nmol/L; 2 alleles, 17.3 [+ or -] 4.7 nmol/L; P = .006). In a multivariate model, circulating AGT emerged as the most important predictor of diastolic pressure (P = .001). In addition, AGT M235T gene polymorphism remained a significant predictor of diastolic BP in a multivariate model adjusted for age, body mass index, fasting glucose, apolipoprotein B, presence of coronary artery disease, and treatment with antihypertensive agents (P < .05). Finally, homozygosity for T235 was associated with increased univariate risk of coronary artery disease and myocardial infarction (odds ratio estimates 1.5; 95% confidence intervals 1.1 to 2.1, P = .03, and 1.0 to 2.1, P = .05, respectively). Conclusions The significant relations observed between the AGT M235T variant, its protein product, and the cardiovascular disease phenotypes provide evidence for a possible role of elevated circulating AGT in the pathogenesis of coronary artery disease. (Am Heart J 1999;137:698-705.) Author Affiliation: Ludwigshafen, Frankfurt, Freiburg, Ulm, and Dusseldorf, Germany, and London, United Kingdom From the Department of Cardiology, Ludwigshafen Heart Center; the Departments of Medicine, Heart Surgery, and Biochemistry, Johann Wolfgang Goethe University, Frankfurt; the Division of Clinical Chemistry, Department of Medicine, Albert Ludwigs University, Freiburg; the Department of Medicine, University Ulm; Institute of Blood Transfusion and Hemostasiology, University Dusseldorf; and the Department of Metabolism and Genetics, St Bartholomew's Hospital, London Article History: Received 12 March 1998; Accepted 12 June 1998 Article Note: (footnote) [star] Supported by research grants from Bristol-Myers Squibb GmbH, Munich, Germany (W.M.), the Commission of the European Community (D.J.G. and W.M.) (EEC Biomed Program PL931211), and Forschungsschwerpunkt Land Baden-Wurttemberg (B.O.B.)., [star][star] Reprint requests: Bernhard R. Winkelmann, MD, Herzzentrum Ludwigshafen, Klinikum der Stadt Ludwigshafen, Bremserstr 79, 67063 Ludwigshafen, Germany., a 0002-8703/99/$8.00 + 0 4/1/92529