Timely topics in medicine. Cardiovascular diseases最新文献

Survival from sudden total occlusion of the left main coronary artery is rare. The majority of these patients suffer major myocardial necrosis accompanied by cardiogenic shock. Case reports and small series of acute left main occlusion present descriptions of electrocardiographic (ECG) changes during the acute phase. Severe ischemia may be manifested in the ECG by life-threatening tachyarrhythmias, conduction disturbances and ST-segment deviation. Because of the potential for life-saving therapeutic options by emergency bypass grafting or immediate stenting, the ECG markers of the serious condition should be recognized by the medical profession. Acute left main occlusion should be suspected in severely ill patients with wide-spread ST-segment depressions, especially in the lateral precordial leads with inverted T waves or ST elevation involving the anterior precordial leads and the lateral extremity leads I and aVL. Also, lead aVR ST elevation accompanied by either anterior ST elevation or widespread ST-segment depression, may indicate left main occlusion. However, as other ECG manifestations have been reported, the absence of these changes should not exclude immediate invasive evaluation of hemodynamically compromised patients. The exact electrophysiological and pathophysiological background for different ECG manifestations of left main occlusion need to be better defined.

Ever since the first embryonic stem cells were isolated in the 1990s scientists and clinicians as well as the general public have followed the development of the field with great attention. As unspecialized cells capable of dividing, renewing and differentiating into specialized cells, stem cells hold great promise as a therapeutic strategy for many diseases, especially those of degenerative nature. In 2006, stem cells were actively investigated in preclinical and clinical settings to manage heart failure, amyotrophic lateral sclerosis, spinal cord injury, stroke, hematologic disorders, renal cell carcinoma, solid tumor cancer, Crohn's disease and cirrhosis, among other disorders. Likewise, biotech and pharmaceutical industry highlighted stem cells and associated products and technologies as useful tools for drug discovery that provide relevant clinical models and ensure efficacious transition of investigational compounds into preclinical testing.

Statins, the most widely prescribed cholesterol-lowering drugs, are considered to be first-line therapeutics for the prevention of coronary heart disease and atherosclerosis. Statins act by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in endogenous cholesterol biosynthesis, which catalyzes the reduction of HMG-CoA to mevalonic acid. Inhibition of this enzyme has proven to be effective for lowering plasma total cholesterol, low-density lipoprotein-cholesterol, and triglyceride levels in humans and can therefore be useful to treat atherosclerotic and dyslipidemic disorders. However, the clinical benefits of statins appear to extend beyond their lipid-lowering effects. Besides reducing cholesterol biosynthesis, inhibition of mevalonate by statins also leads to a reduction in the synthesis of important intermediates, such as the isoprenoids farnesyl pyrophosphate and geranylgeranyl pyrophosphate. These intermediates are involved in the posttranslational prenylation of several proteins (e.g., Ras, Rho, Rac) that modulate a variety of cellular processes including cellular signaling, differentiation, and proliferation. Given the central role of these isoprenylated proteins in endothelial function, atherosclerotic plaque stability, platelet activity, coagulation, oxidation, and inflammatory and immunologic responses, it could be anticipated that these compounds may exert multiple beneficial effects in a broad spectrum of disorders including cardiovascular disease, osteoporosis, Alzheimer's disease and related vascular dementia, viral and bacterial infection, etc. This article summarizes these cholesterol-lowering-independent effects of statins, termed "pleiotropic effects," and the underlying mechanisms, as well as the preclinical experimental approaches that would be useful to evaluate the effects of statins.