Cardiac arrest is a leading cause of death. Even with the best cardiopulmonary resuscitation (CPR), many patients still die or suffer severe organ damage. The reintroduction of blood flow at the start of CPR after systemic ischemia causes additional damage to organs, such as the heart, beyond that caused by the ischemia itself. Ischemia/reperfusion (I/R) injury is a complex pathological event involving processes that can lead to disruptions in the cell membrane and cellular dysfunction. Loss of membrane integrity may allow an influx of calcium (Ca2+) into cardiomyocytes, leading to hypercontracture and cell death. Methods to improve the endogenous membrane resealing capacity of cells that are overwhelmed due to pathological disruptions, such as I/R injury, are needed to prevent cardiomyocyte death, because the ability of the myocardium to regenerate is limited. Using an in-vitro cardiomyocyte model exposed to simulated I/R (hypoxia/reoxygenation, H/R), the tri-block copolymer Poloxamer 188 (P188), with its unique hydrophobic/hydrophilic chemical properties, was administered during reoxygenation and assessed for its ability to provide membrane repair and cellular protection. P188 protected cardiomyocytes from H/R injury by repairing cell membranes, reducing LDH release, and decreasing Ca2+ influx. Additionally, it was shown that the majority of Ca2+ influx during H/R was through tears in the cell membrane, which were targeted by P188, rather than through Ca2+ channels and exchangers not targeted by P188. Determining the mechanism of action of a compound administered during CPR on the cellular dysfunction caused during I/R injury could aid to improve CPR practices in the future.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12032017-114455 |
| Date | 04 December 2017 |
| Creators | Salzman, Michele Marie |
| Contributors | Joey V. Barnett, PhD, Jerod S. Denton, PhD, Janis T. Eells, PhD, Matthias L. Riess, MD, PhD |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-12032017-114455/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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