Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).

Previous studies have shown that proinflammatory cytokines, such as tumor necrosis factor (TNF), are expressed after acute hemodynamic overloading and myocardial ischemia͞infarction. To define the role of TNF in the setting of ischemia͞infarction, we performed a series of acute coronary artery occlusions in mice lacking one or both TNF receptors. Left ventricular infarct size was assessed at 24 h after acute coronary occlusion by triphenyltetrazolium chloride (TTC) staining in wild-type (both TNF receptors present) and mice lacking either the type 1 (TNFR1), type 2 (TNFR2), or both TNF receptors (TNFR1͞TNFR2). Left ventricular infarct size as assessed by TTC staining was significantly greater (P < 0.005) in the TNFR1͞ TNFR2-deficient mice (77.2% ؎ 15.3%) when compared with either wild-type mice (46.8% ؎ 19.4%) or TNFR1-deficient (47.9% ؎ 10.6%) or TNFR2-deficient (41.6% ؎ 16.5%) mice. Examination of the extent of necrosis in wild-type and TNFR1͞TNFR2-deficient mice by anti-myosin Ab staining demonstrated no significant difference between groups; however, the peak frequency and extent of apoptosis were accelerated in the TNFR1͞TNFR2-deficient mice when compared with the wild-type mice. The increase in apoptosis in the TNFR1͞TNFR2-deficient mice did not appear to be secondary to a selective up-regulation of the Fas ligand͞receptor system in these mice. These data suggest that TNF signaling gives rise to one or more cytoprotective signals that prevent and͞or delay the development of cardiac myocyte apoptosis after acute ischemic injury.

European Society of Anaesthesiology.

Neutrophils are potent immune effectors against bacterial infections. Macrophages are important in infections as effectors and regulators, but their exact roles, phenotypic characterization and their relation to neutrophils is incompletely understood. Here we report in a model of bacterial urinary tract infection, one of the most prevalent bacterial infections that tissue-resident Ly6C− macrophages recruited circulating neutrophils and inflammatory Ly6C+ macrophages through chemokines. Neutrophils were primarily recruited through ligands of the chemokine receptor CXCR2, in particular by CXCL1 and less by macrophage migration inhibitory factor (MIF), but not through CXCL5 and CXCL2. Neutrophils, but not Ly6C+ macrophages, cleared the bacteria by phagocytosis. Ly6C+ macrophages instead performed a regulatory function: in response to the infection, they produced the cytokine tumor necrosis factor (TNF), which in turn caused the resident macrophages to secrete CXCL2. This chemokine induced the secretion of matrix metalloproteinase-9 (MMP-9) in neutrophils and allowed these cells to degrade the uroepithelial basement membrane, in order to enter the uroepithelium, the mucosal interface from where the bacteria invade the bladder. Thus, the phagocyte response against bacteria is a highly coordinated event, in which Ly6C− macrophages act as sentinels and Ly6C+ macrophages as innate helper cells. In analogy with T helper cells (Th), we propose to name these helper macrophages (Ph) as they provide a second signal on whether to unleash the principal effector phagocytes, the neutrophils. This cellular triage may prevent ‘false-positive’ immune responses. The role of TNF as innate ‘licensing’ factor contributes to its central role in antibacterial immunity.

Abstract-c-Myc, a protooncogene, mediates both proliferative and cellular growth in many cell types. Although not expressed in the adult heart under normal physiological conditions, Myc expression is rapidly upregulated in response to hypertrophic stimuli. Although Myc is capable of sustaining hyperplastic growth in fetal myocytes, the effects of its re-expression in adult postmitotic myocardium and its role in mediating cardiac hypertrophy are unknown.