The fundamentals of extra-corporeal membrane oxygenation.

During the past 50 years, pharmacologic advancements for cardiovascular risk factors and device innovation for the management of coronary disease, including acute myocardial infarction have radically changed the landscape of heart disease. At present, nearly 25% of individuals develop chronic heart failure after an acute myocardial infarction. It is estimated that nearly 2.6% of the American population suffers from heart failure. In the modern era, miniaturized continuous flow ventricular assist devices are now demonstrating nearly 75% 2-year survival rates with improved patient functionality. As a result, elderly patients with cardiogenic shock for whom medical treatment held minimal promise, may now be viable candidates for advanced mechanical therapies. Given this option, there is a need for more approaches to salvage patients from cardiogenic shock with percutaneously delivered mechanical circulatory support (pMCS) systems. The use of pMCS is growing and now includes patients with acute and chronic heart failure as well as patients undergoing high risk interventional and electrophysiology procedures. Each of these devices has a unique hemodynamic effect and therefore an in-depth understanding of device characteristics is required for optimal patient management. Extracorporeal membrane oxygenation (ECMO) is one of the earliest types of pMCS systems primarily used for cardiorespiratory failure. ECMO can be used in different configurations, which makes it a versatile hemodynamic support device for different patient scenarios. In this paper, the authors review different configurations, indications, and hemodynamic profile of ECMO in respiratory and cardiac failure patients.

Quantitative and qualitative effects of rosuvastatin on LDL-cholesterol: what is the clinical significance?

BACKGROUND: Statins have emerged as the global leader in pharmacologic therapy for dyslipidaemia, and rosuvastatin has demonstrated clinical efficacy as well as safety in several clinical trials and postmarketing analyses. AIM: The present article reviewed the effects of rosuvastatin on the quantity and the quality of low-density lipoproteins (LDL). METHODS: We searched for and reviewed all the available evidence in a systematic way. A literature search (by Medline and Scopus) was performed using the following headings: 'LDL-cholesterol', 'LDL size', 'LDL subclasses', 'small dense LDL', 'apolipoprotein B, apo B' and 'rosuvastatin' up to 11 November 2008. The authors also manually reviewed the references of selected articles for any pertinent material. RESULTS: Rosuvastatin reduces LDL-cholesterol levels to a greater extent than other statins and is able to modulate significantly LDL size and subclasses towards less atherogenic particles as well as the LDL particle number, as indirectly measured by the levels of apo B. DISCUSSION AND CONCLUSIONS: The recent Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin study provides more evidence about the effectiveness of rosuvastatin therapy in reducing cardiovascular risk, even among persons who would not currently be considered for pharmacotherapy. Further insights on cardiovascular outcomes will be available by the on-going trials included in the GALAXY program that includes subjects with type-2 diabetes, haemodialysis recipients, patients with congestive heart failure and specific ethnic groups, such as African American, Hispanic and South Asian populations.

Non-anticoagulant heparin increases endothelial nitric oxide synthase activity: role of inhibitory guanine nucleotide proteins.

Heparin, which is widely used clinically, has recently been shown to have specific properties affecting the vascular endothelium. We hypothesized that heparin stimulates endothelial nitric oxide synthase (eNOS) activity by a mechanism independent of its anticoagulant properties and dependent on an inhibitory guanine nucleotide regulatory protein (Gi). We determined the effect of both heparin and N-acetyl heparin (Non-Hep), a heparin derivative without anticoagulant properties, on eNOS activity in cultured bovine aortic endothelial cells and on endothelium-dependent relaxation in isolated vascular rings. The eNOS activity was determined by measuring both citrulline and nitric oxide (NO) metabolite formation. Heparin and Non-Hep dose-dependently increased basal eNOS activity (ED50 1.0 microgram/ml or 0.15 U/ml), an effect that was significantly inhibited by pertussis toxin (100 ng/ml), a Gi-protein inhibitor. Agonist-stimulated (acetylcholine, 10 microM) eNOS activity was potentiated following pre-treatment with both heparin and Non-Hep and reversed by pertussis toxin. Heparin and Non-Hep induced a dose-dependent relaxation in preconstricted thoracic aortic rings, an effect that was significantly inhibited by pertussis toxin, endothelial inactivation (following treatment with sodium deoxycholate) and NG-nitro-L-arginine-methyl ester (L-NAME). We conclude that heparin and non-anticoagulant heparin induce endothelium-dependent relaxation following activation of eNOS by a mechanism involving a Gi-protein. Administration of heparin derivatives without anticoagulant properties may have therapeutic implications for the preservation of eNOS in conditions characterized by endothelial dysfunction.