A team of investigators, surgical specialists from the Departments of Anesthesiology and Surgery and basic researchers from the Department of Biochemistry & Biophysics, will critically evaluate brain oxygenation and metabolism during and after low flow hypothermic cardiopulmonary bypass (LFCPB) and deep hypothermic circulatory arrest (DHCA). These studies will increase our understanding of the cellular and molecular mechanisms responsible for a brain and retinal dysfunction resulting from cardiopulmonary bypass (CPB) so that effective strategies can be developed for protecting the brain. Specifically, the following hypotheses will be tested: 1. During cardiopulmonary bypass there is a metabolically important deficiency in the oxygen pressure in the brain and retina of newborn piglets. This oxygen deficiency will result in: a/. increases in serum S-100 protein. b/. increases in the extracellular level of dopamine. c/. Increase generation of hydroxyl radicals. d/. induction of expression of heat shock protein. 2. Increases in the extracellular level of dopamine during bypass contributes to development of disturbance of cellular metabolism and cell function through: a/. Generation of free radicals during spontaneous autooxidation of the excess dopamine an during its enzymatic oxidation of monoamine oxidase. b/. Causing alterations in the sensitivity of the D1-like and D2-like receptors by modifying the Kd for agonists and/or the number of receptors (Bma). c/. Causing vasoconstriction which in turn is responsible for post-bypass hypoperfusion. 3. Polyethylene glycol modified hemoglobin (PEG) can provide significant improvements in oxygen delivery and protection from the metabolic disturbances of CPB.
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