Abstract-Clinical studies have reported that the widely used antihyperglycemic drug metformin significantly reduces cardiac risk factors and improves clinical outcomes in patients with heart failure. The mechanisms by which metformin exerts these cardioprotective effects remain unclear and may be independent of antihyperglycemic effects. We tested the hypothesis that chronic activation of AMP-activated protein kinase (AMPK) with low-dose metformin exerts beneficial effects on cardiac function and survival in in vivo murine models of heart failure. Mice were subjected to permanent left coronary artery occlusion or to 60 minutes left coronary artery occlusion followed by reperfusion for 4 weeks. High-resolution, 2D echocardiography was performed at baseline and 4 weeks after myocardial infarction to assess left ventricular dimensions and function. Metformin (125 g/kg) administered to mice at ischemia and then daily improved survival by 47% (PϽ0.05 versus vehicle) at 4 weeks following permanent left coronary artery occlusion. Additionally, metformin given at reperfusion and then daily preserved left ventricular dimensions and left ventricular ejection fraction (PϽ0.01 versus vehicle) at 4 weeks. The improvement in cardiac structure and function was associated with increases in AMPK and endothelial nitric oxide synthase (eNOS) phosphorylation, as well as increased peroxisome proliferatoractivated receptor-␥ coactivator (PGC)-1␣ expression in cardiac myocytes. Furthermore, metformin significantly improved myocardial cell mitochondrial respiration and ATP synthesis compared to vehicle. The cardioprotective effects of metformin were ablated in mice lacking functional AMPK or eNOS. This study demonstrates that metformin significantly improves left ventricular function and survival via activation of AMPK and its downstream mediators, eNOS and PGC-1␣, in a murine model of heart failure. Key Words: myocardial ischemia Ⅲ heart failure Ⅲ metformin Ⅲ nitric oxide H eart failure (HF) is the inability of the heart to meet hemodynamic demands and represents the end stage of various forms of cardiac disease. In the industrialized nations, HF represents a major health problem that has been increasing in prevalence and incidence. In the United States, HF affects more than 5 million people, with 500 000 new cases reported every year. It is responsible for almost 1 million hospital admissions and 40 000 deaths annually. 1 The most important cause of HF is coronary artery disease and acute myocardial infarction, leading to loss of functioning myocytes, development of myocardial fibrosis, and subsequent left ventricular (LV) remodeling, all of which contribute toward the development of LV dysfunction.Metformin is an orally administered biguanide drug that is widely used to lower blood glucose concentrations in patients with diabetes mellitus. Metformin decreases blood glucose by mechanisms different from those of sulfonylureas or insulin and exerts its actions by enhancing insulin sensitivity, inducing greater peripheral uptake of glu...

Based on these data, the IVC and aortic measurements by BUS are not reliable indicators of intravascular volume (as determined by CVP) in acutely ill children.

BACKGROUND: Although under-reported and understudied, unplanned extubations carry a significant risk of patient harm and even death. They are an important yardstick of quality control of care of intubated patients in the ICU. A unit-based risk assessment and multidisciplinary approach is required to decrease the incidence of unplanned extubations. METHODS: As part of a qualityimprovement initiative of Children's Hospital at Montefiore, all planned and unplanned extubations in a multidisciplinary 20-bed pediatric ICU were evaluated over a 12-month period (January to December 2010). At the end of 6 months, an interim analysis was performed, and high-risk patient groups and patient care factors were identified. These factors were targeted in the second phase of the project. RESULTS: Over this period, there were a total of 267 extubations, of which 231 (87%) were planned extubations and 36 (13%) were unplanned. A patient care policy targeting the risk factors was instituted, along with extensive nursing and other personnel education in the second phase. As a result of this intervention, the unplanned extubation rate in the pediatric ICU decreased from 3.55 to 2.59/100 intubation days. All subjects who had an unplanned extubation during nursing procedures or transport required re-intubation, whereas none of the unplanned extubations during ventilator weaning required re-intubation. CONCLUSIONS: A targeted approach based on unit-specific risk factors is most effective in quality-improvement projects. A specific policy for sedation and weaning can be very helpful in managing intubated patients and preventing unintended harm.