Author ORCID Identifier

Defense Date


Document Type


Degree Name

Doctor of Philosophy


Microbiology & Immunology

First Advisor

Wanchun Tang

Second Advisor

Martin Mangino

Third Advisor

Xianjun Fang

Fourth Advisor

Huiping Zhou

Fifth Advisor

Gea-Ny Tseng


We explored the effects of cardiac arrest on mitochondria populations and heart whole tissue lysate proteomics utilizing the Weil Institute’s in vivo rat model of cardiac arrest and cardiopulmonary resuscitation. We have discovered that brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Additionally, complex I is the most sensitive electron transport chain complex to ischemic injury and is a major control point of the rate of oxidative phosphorylation following cardiac arrest and cardiopulmonary resuscitation. Preservation of brain mitochondrial activity and function during cardiac arrest may enhance outcomes and recovery.

A recent article focusing on acute myocardial infarction was able to link S100A8 and S100A9 gene upregulation during ischemia and reperfusion and revealed this caused mitochondrial dysfunction in cardiomyocytes. S100A8 and S100A9 protein expression levels were upregulated in rat LV Apex epicardium whole tissue lysate from animals that experienced global ischemia reperfusion injury via cardiac arrest and cardiopulmonary resuscitation. Further studies are necessary to confirm S100A8 and S100A9 proteins increase expression in brain and heart tissue samples after cardiac arrest and cardiopulmonary resuscitation.

Testing WIN55 as a possible pharmacologic tool, in vitro results indicated that WIN55 was anti-inflammatory. Therefore, we moved to in vivo studies with intramuscular administration of SR141716A (CB1 antagonist) before ventricular fibrillation + cardiopulmonary resuscitation followed by infusion of WIN55 5 min after return of spontaneous circulation. After treatment, plasma concentrations of TNFα, IL6 and IL10 were decreased at return of spontaneous circulation 4hrs. One possible mechanism to drive down proinflammatory cytokine release is binding CB2.


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