H YPOTHERMIA. has been used effectively to protect tissues from irreversible damage caused by circulatory arrest, whether the latter is of accidental occurrence or induced in the course of an operative procedure. Relatively little attention, however, has been given to the possibility of providing such protection by chemical means. Chemical protection against ischemia might be expected to be more easily and quickly induced than hypothermia and to be free of some of the undesirable cardiovascular side effects of the hypothermic state. Three classes of potential protective agents can be envisaged: (1) agents designed to maintain the patency of the vasculature during the ischemia in order to insure complete perfusion of the tissue following its termination; (~) inhibitors of cellular activity that would lower the metabolic demandc of the tissue during the ischemia; (3) physiological compounds, added in excess of their normal concentrations, to forestall the first irreversible changes in the cells. Beneficial effects from pretreating ischemic kidneys with heparin 24 and studies demonstrating extension of the period of permissible cardiac standstill with compounds producing cardioplegia 21,23,2~,37 have suggested the feasibility of the first two approaches. Surprisingly little systematic study has been devoted to the third possibility. Controlled study of cerebral ischemia and of factors modifying its effects has been hampered by the unavailability of suitable experimental preparations. Production of temporary but total arrest of circulation to the
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