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DC Field | Value | Language |
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dc.contributor.advisor | Kim, Paul Y. | - |
dc.contributor.author | Noorzada, Hena | - |
dc.date.accessioned | 2024-07-24T19:44:18Z | - |
dc.date.available | 2024-07-24T19:44:18Z | - |
dc.date.issued | 2024 | - |
dc.identifier.uri | http://hdl.handle.net/11375/29984 | - |
dc.description.abstract | Many initial survivors of cardiac arrest develop disability or die, stemming from post-cardiac arrest syndrome (PCAS), where the complications are secondary to acquired coagulopathy. Shock dysregulates both coagulation and fibrinolysis, but neither is directly treated during resuscitation. This study focuses on 1) characterizing the porcine fibrinolytic system, and 2) studying its temporal changes in a porcine model of cardiac arrest. The optimal conditions needed to generate and degrade porcine plasma clots were assessed. Plasminogen, fibrinogen and tissue-type plasminogen activator (tPA) of either human or porcine origin were tested in all possible permutations. Plasmin generation was monitored using a chromogenic substrate S-2251 and the rates were quantified using time-squared analysis. Porcine fibrin demonstrated preference toward porcine plasminogen and tPA over human counterparts. With human fibrin, all reactions were faster than all-porcine components and species-preference was no longer present. Ventricular fibrillation (VF) arrest was induced in Yorkshire pigs using a transvenous pacer. Blood samples were collected into citrate at five times: baseline (Pre), 1-min post VF (VF1), 8-min post VF (VF8), 5-min post return of spontaneous circulation (ROSC) and death (PM). Plasma was isolated and clot formation and lysis was performed using conditions above. Reactions were monitored by optical density (OD) to determine: 1) clot lysis time (CLT), 2) total OD change (ΔOD; implying clot structure), and 3) baseline OD (implying plasma composition). Transient fibrinolysis resistance was observed; CLT increased by approximately 3-fold at VF8 compared with Pre and decreased thereafter. Both ΔOD and baseline OD showed significant changes during VF compared with Pre, but normalized once ROSC was achieved. Fibrinolysis inhibition was normalized by increasing tPA, suggesting the defect is due to imbalance of the fibrinolytic system. Fibrinolysis can effectively be studied in porcine models. Direct intervention to normalize fibrinolysis during resuscitation may enhance ROSC and reduce reperfusion injury, which may improve outcomes from cardiac arrest. | en_US |
dc.language.iso | en | en_US |
dc.title | Characterization of the Porcine Fibrinolytic System and Identifying its Temporal Changes in a Porcine Model of Cardiac Arrest | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Medical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science in Medical Sciences (MSMS) | en_US |
dc.description.layabstract | Cardiac arrest occurs when the heart suddenly stops beating effectively, leading to insufficient blood circulation, a life-threatening situation. It is common for the patient to suffer blood clotting issues during and after the attack, but whether the blood clot removal system (fibrinolysis) is also affected is unknown. To study this, an established pig model of cardiac arrest was used. Once we confirmed that studying fibrinolysis in pig blood samples using our methods and reagents was possible, samples obtained from pigs undergoing cardiac arrest were analyzed. The fibrinolytic system was impaired during the early stages of cardiac arrest, with changes to the clot properties. Also, the impairment was mostly due to the fibrinolytic system, and not other components such as cell-free DNA. Our findings suggest that treatments to improve fibrinolysis during resuscitation could be a potential target for improved patient outcome in cardiac arrest. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Noorzada_Hena_FinalSubmission2024July_MSc.pdf | 4.16 MB | Adobe PDF | View/Open |
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