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Browsing by Author "Wang, I-wen"

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    Extra Corporeal Membrane Oxygenation (ECMO) review of a lifesaving technology
    (AME Publishing Company, 2015-07) Makdisi, George; Wang, I-wen; Department of Medicine, IU School of Medicine
    Extra Corporeal Membrane Oxygenation (ECMO) indications and usage has strikingly progressed over the last 20 years; it has become essential tool in the care of adults and children with severe cardiac and pulmonary dysfunction refractory to conventional management. In this article we will provide a review of ECMO development, clinical indications, patients' management, options and cannulations techniques, complications, outcomes, and the appropriate strategy of organ management while on ECMO.
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    Intracellular Ca2+ Dysregulation in Coronary Smooth Muscle Is Similar in Coronary Disease of Humans and Ossabaw Miniature Swine
    (Springer, 2022-02) Badin, Jill K.; Eggenberger, Caleb; Rodenbeck, Stacey Dineen; Hashmi, Zubair A.; Wang, I-wen; Garcia, Jose P.; Alloosh, Mouhamad; Sturek, Michael; Anatomy and Cell Biology, School of Medicine
    Intracellular free Ca2+ ([Ca2+]i) dysregulation occurs in coronary smooth muscle (CSM) in atherosclerotic coronary artery disease (CAD) of metabolic syndrome (MetS) swine. Our goal was to determine how CAD severity, arterial structure, and MetS risk factors associate with [Ca2+]i dysregulation in human CAD compared to changes in Ossabaw miniature swine. CSM cells were dispersed from coronary arteries of explanted hearts from transplant recipients and from lean and MetS swine with CAD. CSM [Ca2+]i elicited by Ca2+ influx and sarcoplasmic reticulum (SR) Ca2+ release and sequestration was measured with fura-2. Increased [Ca2+]i signaling was associated with advanced age and a greater media area in human CAD. Decreased [Ca2+]i signaling was associated with a greater number of risk factors and a higher plaque burden in human and swine CAD. Similar [Ca2+]i dysregulation exhibited in human and Ossabaw swine CSM provides strong evidence for the translational relevance of this large animal model.
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    Mesenchymal Stem Cell Secretions Improve Donor Heart Function 1 Following Ex-vivo Cold Storage
    (Elsevier, 2020) Wang, Meijing; Yan, Liangliang; Li, Qianzhen; Yang, Yang; Turrentine, Mark; March, Keith; Wang, I-wen; Surgery, School of Medicine
    Objectives Heart transplantation is the gold standard of treatments for end-stage heart failure, but its use is limited by extreme shortage of donor organs. The time “window” between procurement and transplantation sets the stage for myocardial ischemia/reperfusion injury, which constrains the maximal storage time and lowers use of donor organs. Given mesenchymal stem cell (MSC)-derived paracrine protection, we aimed to evaluate the efficacy of MSC-conditioned medium (CM) and extracellular vesicles (EVs) when added to ex vivo preservation solution on ameliorating ischemia/reperfusion–induced myocardial damage in donor hearts. Methods Mouse donor hearts were stored at 0°C-4°C of <1-hour cold ischemia (<1hr-I), 6hr-I + vehicle, 6hr-I + MSC-CM, 6hr-I + MSC-EVs, and 6hr-I + MSC-CM from MSCs treated with exosome release inhibitor. The hearts were then heterotopically implanted into recipient mice. At 24 hours postsurgery, myocardial function was evaluated. Heart tissue was collected for analysis of histology, apoptotic cell death, microRNA (miR)-199a-3p expression, and myocardial cytokine production. Results Six-hour cold ischemia significantly impaired myocardial function, increased cell death, and reduced miR-199a-3p in implanted hearts versus <1hr-I. MSC-CM or MSC-EVs in preservation solution reversed the detrimental effects of prolong cold ischemia on donor hearts. Exosome-depleted MSC-CM partially abolished MSC secretome-mediated cardioprotection in implanted hearts. MiR-199a-3p was highly enriched in MSC-EVs. MSC-CM and MSC-EVs increased cold ischemia–downregulated miR-199a-3p in donor hearts, whereas exosome-depletion neutralized this effect. Conclusions MSC-CM and MSC-EVs confer improved myocardial preservation in donor hearts during prolonged cold static storage and MSC-EVs can be used for intercellular transport of miRNAs in heart transplantation.
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