Initially, more than half of the cardiac arrests that occur can be resuscitated successfully, but long-term survival and recovery of neurologic function are limited by metabolic failure in the central nervous system. In addition, there are no physiological variables, which can be measured soon after resuscitation, that can be used to predict long-term morbidity and mortality. It continues to be the long-term goal of this project to investigate the metabolic pathophysiological response to cardiac arrest and resuscitation in rat model in order to 1) discover measurable variables which predict survival and neurologic outcome, and 2) provide theoretical underpinning for development of treatment strategies to improve overall brain resuscitation rates and decrease neuronal loss of function. Intracellular pH has been thought to play a central role in brain damage in ischemia, due to both primary acidification during ischemia and delayed swelling accompanying alkalinization during reperfusion. This hypothesis will be directly tested in the proposed experimental protocols both in the in vitro hippocampal slice preparation and by microregional measurement of cerebral blood flow by autoradiographic methods, by gross regional determinations of tissue wet weight to dry weight ratios, and by microregional measurements of intracellular pH through the application of color film histophotometry of the pH indicator dye neutral red in rat brain frozen in situ after cardiac arrest and resuscitation. Potential treatment strategies intended to reverse the loss of the brain adenylate pool by adenosine administration; to counteract the osmotically driven cellular edema by hyperosmotic solutions; and, to decrease cell water that accumulates through the activity of the amiloride-sensitive Na+/H+ exchanger by administration of specific inhibitors will be applied in the early hours after resuscitation and provide a focus for monitoring and manipulating the critical metabolic variables that may be responsible for cerebral death and delayed specific neuronal loss.
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