Global brain ischemia and reperfusion

Brian J. Oneil, Raymond C. Koehler, Robert W. Neumar, Uwe Ebmeyer, Gary S. Krause

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Introduction: Sudden, unexpected death claims nearly 1000 lives each day in the United States and is the fifth leading cause of all deaths in the western world. Cardiac arrest occurs over 300 000 times per year both in the United States and Europe with the risk for persons 35 years and older estimated at 1 per 1000. In those patients resuscitated from cardiac arrest, nearly 60% die from a neurological cause. Despite every effort, only 3%-10% of all resuscitated patients are able to resume their former lifestyles. To date, there are no clinically effective pharmacologic tools for amelioration of brain damage by ischemia and reperfusion. Clinical trials conducted more than a decade ago utilizing postresuscitation treatment with barbiturates or calcium antagonists were disappointing. More recently, clinical treatment of stroke with a radical scavenger (trilazad), intercellular adhesion molecule-1 antagonist (Enlimomab), glutamate receptor antagonist (Aptiganel, gavestinel), glutamate release inhibitor (Lubeluzole), ganglioside administration (GM1), calcium channel blockade, or upregulation of the GABA receptor (Clomethiazole) were all found ineffective. This suggests that our understanding of the mechanisms involved in damage and repair in neurons remains incomplete and further therapeutic progress will require the delineation of the primary mechanisms involved in neuronal injury and repair. Although the picture is still incomplete, a few things are clear. The majority of damage occurs not during ischemia but during reperfusion. Nevertheless, the two processes work sequentially to increase neuronal damage (i.e., lipolysis during ischemia potentiates the radicalmediated peroxidation of polyunsaturated fatty acids (PUFAs) during reperfusion).

Original languageEnglish (US)
Title of host publicationCardiac Arrest
Subtitle of host publicationThe Science and Practice of Resuscitation Medicine
PublisherCambridge University Press
Pages236-281
Number of pages46
Volume9780521847001
ISBN (Electronic)9780511544828
ISBN (Print)05218470041, 9780521847001
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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