Activated protein C in patients with septic shock: a consecutive case series.

Background: The recommendation to restrict the use of activated protein C (APC) to patients with severe sepsis and the highest risk of death originates from large trials that were subject to major exclusion criteria.

Objective: To investigate the effect of APC on prognosis in 'real world' patients.

Method: Consecutive case series at tertiary care hospital including 63 adults with septic shock and multi-organ failure treated with APC (24 mcg/kg/h) for up to 96 h in addition to standard care.

Receptors for acylethanolamides-GPR55 and GPR119.

Acylethanolamides are lipid substances widely distributed in the body, generated from a membrane phospholipid precursor, N-acylphosphatidylethanolamine (NAPE). The recent identification of arachidonoyl ethanolamide (anandamide or AEA) as an endogenous cannabinoid ligand has focused attention on acylethanolamides, which has further increased with the subsequent identification of related additional acylethanolamides with signaling function, such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Most of the biological functions of anandamide are mediated by the two G protein-coupled cannabinoid receptors identified to date, CB(1) and CB(2), with the transient receptor potential vanilloid-1 receptor being an additional potential target.

Progression of left ventricular functional abnormalities in hypertensive patients with heart failure: an ultrasonic two-dimensional speckle tracking study.

Objective: Two-dimensional (2-D) strain imaging is a novel echocardiographic technique for myocardial function evaluation. We sought to investigate left ventricular (LV) systolic function in patients with heart failure caused by hypertension using a 2-D strain approach and to validate this method against Doppler strain measurements.

Methods: The study population comprised 81 patients (66.

2-Arachidonylglycerol acting on CB1 cannabinoid receptors mediates delayed cardioprotection induced by nitric oxide in rat isolated hearts.

Endocannabinoids have been implicated in protective effects in the heart and brain, but the mechanism of possible infarct-size-reducing effects remains controversial. Using a model of delayed preconditioning (PC), rats received the nitric oxide (NO) donor nitroglycerin (0.15 mg/h/kg) for 24 hours via transdermal application.

Coronary vasodilator effects of endogenous cannabinoids in vasopressin-preconstricted unpaced rat isolated hearts.

The mechanisms by which cannabinoids alter coronary vascular tone and cardiac performance are controversial. We investigated the effects of various cannabinoids in spontaneously beating Langendorff-perfused rat hearts. Bolus injections of anandamide (0.

The endocannabinoid arachidonyl ethanolamide (anandamide) increases pulmonary arterial pressure via cyclooxygenase-2 products in isolated rabbit lungs.

Several cannabinoids elicit systemic vasodilation, mainly via CB1 cannabinoid and vanilloid receptors. However, effects in the pulmonary circulation are unknown. Using the isolated, ventilated, buffer-perfused rabbit lung, we have shown that the endocannabinoids arachidonyl ethanolamide (anandamide) and 2-arachidonyl glycerol (2-AG) dose-dependently increase pulmonary arterial pressure (+19.

Cannabinoid antagonist SR-141716 inhibits endotoxic hypotension by a cardiac mechanism not involving CB1 or CB2 receptors.

Endocannabinoids and CB1 receptors have been implicated in endotoxin (LPS)-induced hypotension: LPS stimulates the synthesis of anandamide in macrophages, and the CB1 antagonist SR-141716 inhibits the hypotension induced by treatment of rats with LPS or LPS-treated macrophages. Recent evidence indicates the existence of cannabinoid receptors distinct from CB1 or CB2 that are inhibited by SR-141716 but not by other CB1 antagonists such as AM251. In pentobarbital-anesthetized rats, intravenous injection of 10 mg/kg LPS elicited hypotension associated with profound decreases in cardiac contractility, moderate tachycardia, and an increase in lower body vascular resistance.

Lipopolysaccharide induces anandamide synthesis in macrophages via CD14/MAPK/phosphoinositide 3-kinase/NF-kappaB independently of platelet-activating factor.

Macrophage-derived endocannabinoids have been implicated in endotoxin (lipopolysaccharide (LPS))-induced hypotension, but the endocannabinoid involved and the mechanism of its regulation by LPS are unknown. In RAW264.7 mouse macrophages, LPS (10 ng/ml) increases anandamide (AEA) levels >10-fold via CD14-, NF-kappaB-, and p44/42-dependent, platelet-activating factor-independent activation of the AEA biosynthetic enzymes, N-acyltransferase and phospholipase D.

CB(1) cannabinoid receptor antagonism promotes remodeling and cannabinoid treatment prevents endothelial dysfunction and hypotension in rats with myocardial infarction.

1. To study the long-term effects of altered cannabinoid receptor activity on myocardial and vascular function, Wistar rats were treated with the selective CB(1) antagonist AM-251 (0.5 mg kg(-1) d(-1)), the potent synthetic cannabinoid HU-210 (50 micro g kg(-1) d(-1)) or vehicle for 12 weeks after coronary artery ligation or sham operation.

Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle.

Cannabinoids elicit hypotension mainly via activated CB(1) receptors and show complex cardiovascular actions. Effects on human heart muscle have not been studied yet. Isolated human atrial heart muscle preparations were stimulated by electrical field with 1 Hz to contract isometrically at optimal length and were challenged with the endogenous cannabinoid arachidonyl ethanolamide (anandamide), the metabolically stable analogue R-methanandamide, and the potent synthetic CB(1) receptor agonist HU-210.