Postischemic Hyperoxia and Cerebral Energy Metabolism

University Of Maryland Baltimore, Baltimore MD

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Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] Our current area of interest is the effects of oxygen tension during the reperfusion period following cerebral ischemia. Specifically, our proposed research investigates the role of oxidative stress in reperfusion injury. We propose to study the difference between hyperoxic (100% O2) versus normoxic (21% O2) reperfusion following a 10 minute clinically relevant model of canine cardiac arrest and resuscitation. We hypothesize that hyperoxic resuscitation leads to increased oxidative stress which targets key metabolic enzymes, causing decreased enzyme activity and lower cellular glucose metabolism. We will utilize nuclear magnetic resonance spectroscopy to monitor metabolism of [1]-13C-glucose in postischemic animals resuscitated with either hyperoxia or normoxia. To investigate changes in metabolic enzyme activity, we will focus on the pyruvate dehydrogenase complex (PDHC), a mitochondrial enzyme that catalyzes the oxidative decarboxylation of pyruvate to acetyl-coenzyme A. We hypothesize that oxidative stress increases following ischemia/reperfusion and targets the PDHC, causing decreased enzyme activity. 3-nitrotyrosine, a marker of oxidative stress will be implemented to monitor targeting of oxidative stress to the PDHC. [unreadable] [unreadable] [unreadable]