[Monoamine metabolism after transient global ischemia. Mechanism of delayed postischemic hypoperfusion]

During the period of recirculation following transient global ischemia, an initial hyperemia is succeeded by a secondary decrease in cerebral blood flow, termed "delayed postischemic hypoperfusion." It has been suggested that this phenomenon can lead to additional brain damage after the initial ischemic insult. One proposed mechanism of delayed postischemic hypoperfusion is increased cerebrovascular smooth muscle tone. Release of vasoactive amines, formation of vasoactive products of arachidonic acid metabolism, and disturbance of calcium ion homeostasis in cerebrovascular smooth muscle may contribute to postischemic vasoconstriction. In this study, monoamine metabolism following transient global ischemia was investigate. Mongolian gerbils subjected to 15 minutes of temporal bilateral common carotid artery occlusion and up to 6 hours of recirculation were employed as a model of transient global ischemia. In this model, secondary energy failure reportedly occurs after 6 hours of recirculation. Regional cerebral concentrations of monoamines and their metabolites were determined by high-performance liquid chromatography with electrochemical detection. After 4 to 6 hours of recirculation, accumulation of vasoactive amine, 5-hydroxytryptamine, its major metabolite, 5-hydroxyindole acetic acid, and its precursor amino acid, tryptophan were detected. This finding strongly suggests a postischemic increase in both synthesis and release of this amine, which may explain postischemic vasoconstriction. Moreover, increased dopamine synthesis and release after 1 hour of recirculation was suggested. As dopamine release is reported to increase cerebral glucose utilization, its elevation may contribute to an increase in cerebral energy demand after ischemia. Thus, the brain becomes relatively ischemic and secondary ischemic cell damage occurs.