Academic Journal
Pefluorocarbon inhibition of bubble induced Ca 2+ transients in an in vitro model of vascular gas embolism
| العنوان: | Pefluorocarbon inhibition of bubble induced Ca 2+ transients in an in vitro model of vascular gas embolism |
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| المؤلفون: | Klinger, Alexandra L, Kandel, Judith, Pichette, Benjamin, Eckmann, David M |
| المصدر: | Experimental Biology and Medicine ; volume 239, issue 1, page 116-122 ; ISSN 1535-3702 1535-3699 |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2013 |
| المجموعة: | Frontiers (Publisher - via CrossRef) |
| الوصف: | Endothelial injury resulting from deleterious interaction of gas microbubbles occurs in many surgical procedures and other medical interventions. The symptoms of vascular air embolism (VAE), while serious, are often difficult to detect, and there are essentially no pharmaceutical preventative or post-event treatments currently available. Perfluorocarbons (PFCs), however, have shown particular promise as a therapeutic option in reducing endothelial injury both in- and ex-vivo. Recently, we demonstrated the effectiveness of Oxycyte, a third-generation PFC formulated in a phosphotidylcholine emulsion, using an in vitro model of VAE developed in our laboratory. This apparatus allows live cell imaging concurrent with precise manipulation of physiologically sized microbubbles so that they may be brought into individual contact with human umbilical vein endothelial cells dye-loaded with the Ca 2+ sensitive Fluo-4. Herein, we expand use of this fluorescence microscopy-based cell culture model. Specifically, we examined the concentration dependence of Oxycyte in reducing both the amplitude and frequency of large intracellular Ca 2+ currents that are both a hallmark of bubble contact and a quantifiable indication that abnormal intracellular signaling has been triggered. We measured dose dependence curves and fit the resultant data using a modified Black and Leff operational model of agonism. The half maximal inhibitory concentrations of Oxycyte for (i) inhibition of occurrence and (ii) amplitude reduction were 229 ± 49 µM and 226 ± 167 µM, respectively. This investigation shows the preferential gas/liquid interface occupancy of the PFC component of Oxycyte over that of mechanosensing glycocalyx components and validates Oxycyte’s specific surfactant mechanism of action. Further, no lethality was observed for any concentration of this bioinert PFC, as it acts as a competitive allosteric inhibitor of syndecan activation to ameliorate cell response to bubble contact. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1177/1535370213506434 |
| الاتاحة: | http://dx.doi.org/10.1177/1535370213506434 http://journals.sagepub.com/doi/pdf/10.1177/1535370213506434 http://journals.sagepub.com/doi/full-xml/10.1177/1535370213506434 |
| Rights: | http://journals.sagepub.com/page/policies/text-and-data-mining-license |
| رقم الانضمام: | edsbas.79D3CEDF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1177/1535370213506434 |
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