ABSTRACT
Unrecognized central venous catheter (CVC) infiltration is an uncommon but potentially life-threatening complication. For instance, a malpositioned subclavian line can infuse into the mediastinum, pleural cavity, or interstitial space of the neck. We present the case of a 30-year-old male with gunshot wounds to the right chest, resuscitated with an initially functional left subclavian CVC, which later infiltrated into the neck causing compression of the carotid sinus and consequent bradycardic arrest. Return of spontaneous circulation (ROSC) was achieved following intravenous epinephrine, cardiac massage, and emergency neck exploration and cervical fasciotomy. Our case highlights the importance of frequent reassessment of lines, especially those placed during fast-paced, high-intensity clinical situations. We recommend being mindful when using rapid transfusion devices as an interstitial catheter may not mount enough back pressure to trigger the system's alarm before significant tissue damage or compartment syndrome occurs.
ABSTRACT
Interferon-α (IFN-α) is essential for antiviral immunity, but in the absence of matrix metalloproteinase-12 (MMP-12) or IκBα (encoded by NFKBIA) we show that IFN-α is retained in the cytosol of virus-infected cells and is not secreted. Our findings suggest that activated IκBα mediates the export of IFN-α from virus-infected cells and that the inability of cells in Mmp12(-/-) but not wild-type mice to express IκBα and thus export IFN-α makes coxsackievirus type B3 infection lethal and renders respiratory syncytial virus more pathogenic. We show here that after macrophage secretion, MMP-12 is transported into virus-infected cells. In HeLa cells MMP-12 is also translocated to the nucleus, where it binds to the NFKBIA promoter, driving transcription. We also identified dual-regulated substrates that are repressed both by MMP-12 binding to the substrate's gene exons and by MMP-12-mediated cleavage of the substrate protein itself. Whereas intracellular MMP-12 mediates NFKBIA transcription, leading to IFN-α secretion and host protection, extracellular MMP-12 cleaves off the IFN-α receptor 2 binding site of systemic IFN-α, preventing an unchecked immune response. Consistent with an unexpected role for MMP-12 in clearing systemic IFN-α, treatment of coxsackievirus type B3-infected wild-type mice with a membrane-impermeable MMP-12 inhibitor elevates systemic IFN-α levels and reduces viral replication in pancreas while sparing intracellular MMP-12. These findings suggest that inhibiting extracellular MMP-12 could be a new avenue for the development of antiviral treatments.
