Deleterious effect of glucose pretreatment on recovery from diffuse cerebral ischemia in the cat. II. Regional metabolite levels.

Abstract

SUMMARY Glucose was Infused intravenously into cats prior to cerebral ischemia. Brain concentrations of glucose, measured in 7 regions, were elevated 2.5-fold compared to those of non-infused animals. Ischemia of 15 or 30 minutes duration caused a greater accumulation of lactic add in the brain of glucose-infused animals. Post-iscbemic restitution of cerebral ATP, phospbocreatine, and lactate during 90 minutes of reclrculation was severely impaired in the brain of animals pretreated with glucose compared to untreated animals. Thus, excess lactic addosis may be a major factor interfering with metabolic restitution following cerebral ischemia. Stroke, Vol 11, No 4, 1980CEREBRAL ISCHEMIA causes rapid depletion of the brain's stores of high energy phosphates -ATP and phosphocreatine. 1 "' Recirculation following defined periods of ischemia leads, in many models, to nearly complete recovery of brain levels of ATP and phosphocreatine.1 "* Recently, however, we have described regionally heterogeneous recovery of brain blood flow and metabolite levels following 30 minutes, but not 15 minutes, of ischemia in the cat. '8 Thus, a 90-minute recirculation period following a 30-minute ischemic insult produced regions in which ATP and phosphocreatine levels were less than 10% of control."In the present study we have examined the effect of pre-ischemic administration of glucose on restitution of metabolite levels following 15 or 30 minutes of ischemia. Glucose administration has previously been shown to increase the neurologic deficit and degree of neuropathologic damage caused by cardiac arrest in the monkey. "11 Since post-ischemic recovery of brain function depends upon restoration of an adequate energy state, we have compared restitution of energy metabolites in glucose-treated versus untreated animals which have been described previously. 1 In the accompanying report 18 we have examined the effect of glucose infusion on post-ischemic cerebral blood flow. MethodsCats of either sex, weighing 3-4 kg, were anesthetized with sodium pentobarbital, 40 mg/kg intraperitoneally, and were prepared as previously described.1 ' The common carotid arteries were isolated and encircled with loose-fitting ligatures, and the basilar artery was exposed through the clivus. One

Local Cerebral Glucose Utilization in Chronic Middle Cerebral Artery Occlusion in the Cat

“…In the bound ary MCA territory, the observed depression in LCMRgIc was out of proportion to the degree of neuronal cell damage. This finding is in agreement with the data of Paschen et al (1983) and Welsh et al (1980), who reported that the distribution of fo cal energy failure within the cortex was most sig nificant in the boundary zone. It is noteworthy that LCMRglc of the non-MCA territory in all three groups exhibited a significant depression that was not accompanied by proportional histological dam age, suggesting that this may be a purely functional response, i.e., diaschisis.…”

NADH Fluorescence and Regional Energy Metabolites during Focal Ischemia and Reperfusion of Rat Brain

“…Areas without reflow retain high levels of NADH for several hours (Welsh et al, 1987). Sec ond, the diminution of NADH fluorescence in the ischemic core was similar to that observed previ ously in models of transient, global ischemia (Welsh et al, 1980(Welsh et al, , 1982a and hypoxia-ischemia in neona tal rats (Welsh et al, 1982b) and following transient MCA occlusion in cats (Paschen et al, 1985). In these previous studies, regions with impaired en ergy metabolism exhibited abnormally diminished NADH fluorescence, suggesting that defective gen eration of NADH may limit the production of high energy phosphates (Welsh et al, 1982a).…”

Brain Metabolic Correlates of Hypoxic-Ischemic Cerebral Necrosis in Mid-Gestational Sheep Fetuses: Significance of Hypotension

“…Previous studies from our laboratory (Myers, 1977(Myers, , 1979aMyers et al , 1983Myers et al , , 1984 and re cently from others (Welsh et al , 1980;Kalimo et al , 1981;Rehncrona et al , 1981) have demon strated that lactic acid accumulation in brain above a threshold concentration of 17 -20 f,Lmol/g in adult cats or monkeys serves as the basis for brain edema and tissue necrosis. Further, although a decrease in energy charge is a precondition for the generation of high lactic acid concentrations in brain, a de creased energy charge by itself is insufficient to in jure the brain (Myers, 1981).…”