Multimodal Elimination for Intoxication with a Lethal Dose of Organic Mercury.

We here report on a case of massive organic mercury intoxication in a 40-year-old man that resulted in progressive multiorgan failure. We treated the patient intravenously and enterally with the chelating agent (RS)-2,3-bis(sulfanyl) propane-1-sulfonic acid (DMPS) in addition to hemodialysis. The patient was treated for 6 weeks and could successfully be weaned from mechanical ventilation and hemodialysis. He awoke and was sent to rehabilitation, but unfortunately died 7 months later from refractory status epilepticus. Autopsy revealed severe brain atrophy consistent with organ damage from massive mercury intoxication. The present case illustrates that bimodal DMPS application is sufficient for detoxification from lethal mercury levels, with an associated chance for weaning of organ support and survival to discharge. The case further reminds us of intoxication as a cause of multiorgan dysfunction. We propose to immediately initiate combined parenteral and enteral detoxification in cases of methyl mercury intoxication, especially in cases of high doses.

ECMO in cardiac arrest and cardiogenic shock.

Cardiogenic shock is an acute emergency, which is classically managed by medical support with inotropes or vasopressors and frequently requires invasive ventilation. However, both catecholamines and ventilation are associated with a worse prognosis, and many patients deteriorate despite all efforts. Mechanical circulatory support is increasingly considered to allow for recovery or to bridge until making a decision or definite treatment. Of all devices, extracorporeal membrane oxygenation (ECMO) is the most widely used. Here we review features and strategical considerations for the use of ECMO in cardiogenic shock and cardiac arrest.

[Extracorporeal membrane oxygenation : Principles and medical indications]. / Extrakorporale Membranoxygenierung : Prinzip und internistische Indikationen.

Extracorporeal membrane oxygenation (ECMO) is a special form of a miniaturized heart-lung machine with the ultimate goal to stabilize critically ill patients. Dependent on the cannulation strategy ECMO can support or replace heart and/or lung function. Medical indications and contraindications have to be evaluated thoroughly before cannulation. Moreover, before ECMO initiation a solid treatment aim has to be defined: bridge to recovery, bridge to decision, bridge to transplantation, and bridge to destination (i. e. implantation of a permanent assist device). Regarding invasiveness of the system, potential life-threatening complications, requirement of standardized monitoring of the patient and the device as well as tertiary care infrastructure, ECMO should exclusively be used in highly experienced tertiary centers.

Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury.

Maladaptive remodelling of the arterial wall after mechanical injury (e. g. angioplasty) is characterised by inflammation, neointima formation and media hypertrophy, resulting in narrowing of the affected artery. Moreover, mechanical injury of the arterial wall causes loss of the vessel protecting endothelial cell monolayer. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, regulates inflammation, cell migration and proliferation, essential processes for vascular remodelling and re-endothelialisation. Therefore, we investigated the role of MK2 in remodelling and re-endothelialisation after arterial injury in genetically modified mice in vivo. Hypercholesterolaemic low-density-lipoprotein-receptor-deficient mice (ldlr-/-) were subjected to wire injury of the common carotid artery. MK2-deficiency (ldlr-/-/mk2-/-) nearly completely prevented neointima formation, media hypertrophy, and lumen loss after injury. This was accompanied by reduced proliferation and migration of MK2-deficient smooth muscle cells. In addition, MK2-deficiency severely reduced monocyte adhesion to the arterial wall (day 3 after injury, intravital microscopy), which may be attributed to reduced expression of the chemokine ligands CCL2 and CCL5. In line, MK2-deficiency significantly reduced the content of monocytes, neutrophiles and lymphocytes of the arterial wall (day 7 after injury, flow cytometry). In conclusion, in a model of endothelial injury (electric injury), MK2-deficiency strongly increased proliferation of endothelial cells and improved re-endothelialisation of the arterial wall after injury. Deficiency of MK2 prevents adverse remodelling and promotes endothelial healing of the arterial wall after injury, suggesting that MK2-inhibition is a very attractive intervention to prevent restenosis after percutaneous therapeutic angioplasty.

Extrinsic Notch ligand Delta-like 1 regulates tip cell selection and vascular branching morphogenesis.

RATIONALE: In developing blood vessels, single endothelial cells (ECs) specialize into tip cells that sense vascular endothelial growth factor (VEGF) and contribute to vessel sprouting and branch formation. Tip cell differentiation is inhibited through lateral Notch signaling between ECs, which is controlled by Notch ligands expressed in vessel sprouts. The contribution of the Notch ligand Delta-like (Dll) 1 herein is unknown. OBJECTIVE: To investigate the role of Dll1 in vascular morphogenesis and tip cell formation in the mouse retina. METHODS AND RESULTS: Mice with heterozygous deletion of Dll1 had fewer tip cells during angiogenic sprouting of the superficial vascular plexus but also showed impaired vessel branching into deeper retinal layers and impaired deep plexus angiogenesis. Interestingly, the formation of vertical branches was also guided by filopodia-extending ECs located at the tip of branches, consistent with tip cells, which emerged from established vessels to form a secondary plexus within the deeper neuronal cell layers. During both phases of vascular patterning, Dll1 was not expressed in ECs but in the superficial neuronal layer in close contact with expanding vessels, where Dll1 expression coincided with tip cell formation in a spatiotemporal manner. In vitro, culture of ECs on DLL1 induced essential tip cell genes, including Dll4, VEGF receptor 3, and ephrin-B2, and stimulated VEGF responsiveness and vascular network formation. CONCLUSIONS: Dll1 acts as an extrinsic cue involved in tip cell selection, which directs vessel sprouting and branch formation.