Glucose-associated alterations in ischemic brain metabolism of neonatal piglets.

Abstract

Background and Purpose: During global brain ischemia or hypoxia-ischemia in adults, hyperglycemia is deleterious to the brain. In contrast, similar adverse effects have not been found in neonatal animals. This investigation examined neonatal piglets to determine if there were specific alterations of ischemic brain metabolism associated with different systemic glucose concentrations and to potentially clarify the effects of hyperglycemia during ischemia in neonates.Methods: Two groups of animals (n=12 in each group) were studied during partial ischemia to compare the effects of hyperglycemia (plasma glucose concentration, 258+97 mg% [mean±SD]) with modest hypoglycemia (plasma glucose concentration, 62 ±23 mg%). A broad spectrum of cerebral blood flow reduction was achieved by combining inflation of a cervical pressure cuff with varying degrees of hemorrhagic hypotension. High-energy phosphorylated metabolites, intracellular pH, and cerebral blood flow were simultaneously measured using a magnetic resonance spectroscopic technique. Brain metabolic variables (/J-ATP, inorganic phosphorus, phosphocreatine, intracellular pH) were plotted as a function of blood flow reduction during partial ischemia for each group.Results: During ischemia values of cerebral blood flow were comparably distributed between groups and ranged from 15% to 110% of those of control. At a given reduction of cerebral blood flow, hyperglycemic piglets maintained a higher concentration of/J-ATP (p=0.011) and had a smaller increase in inorganic phosphorus (p<0.001). At cerebral blood flow <50% of control, the intracellular pH of piglets with modest hypoglycemia during partial ischemia was never reduced to <6.46, whereas intracellular pH fell as low as 5.97 for hyperglycemic animals.Conclusions: ATP preservation may account for the differing effects of glucose during ischemia in neonates compared with adults, provided that the accentuated brain acidosis is not deleterious to neonatal brain tissue. (Stroke 1992;23:1504-1511 KEY WORDS • cerebral ischemia • cerebral metabolism • glucose • nuclear magnetic resonance • pigs

Brain Cell Membrane Function during Hypoxia in Hyperglycemic Newborn Piglets

“…This finding is consistent with previous studies in newbo rn animals that demonstrated that hyperglycemia either had no significant effect on the cereb ral response to hypoxia/ischemia (13,29) or improved outcome as indicated by improved surviva l (16,30) or decreased infarct size (31). In contra st, severa l studi es of cerebral hypoxia/ischemi a in adult animals found that hyperglycemia during or after the insult is associated with decre ased survival (32,33), signific ant increases in cereb ral lactate concentration, and reduced intracellular pH (7,9), as well as more extensive neuronal necros is and infarct size (4,33,34).…”

“…In the newborn, the effect of decreased substrate availability with subsequent energy depletion may be more critical than the accumulation of lactate and development of tissue acidosis (17). Hyperglycemia may be associated with better preservation of levels of high-energy phosphates during hypoxia/ischemia in both adults (37) and newborns (29), although Wagn er et al (4) found no difference in ATP levels during ischemia in hyperglycemic versus normoglycemic adult cats. The study design used in the present investigation precluded measurement of the effect of hyperglycemia on preservation of cerebral levels of high-en ergy phosphates during hypoxia, inasmuch as FiO z was adjusted to produce comparabl e reduction s in PCr in untreated and hypergl ycemic animals (Fig.…”

Effects of Exogenous Glucose on Brain Ischemia in Ovine Fetuses

“…Since that time, hyperglycemia has been shown in numerous studies to exacerbate ischemic damage (12)(13)(14)(15)(16). Because hyperglycemia also increases intraischemic lactic acid levels (27)(28)(29), it was reasonable to conclude that lactic acidosis itself exacerbates the ischemic brain damage during hyperglycemia. However, the role of glucose in brain injury in the adult as well as juvenile or fetal animals is far from resolved because many studies have failed to show detrimental effects resulting from glucose infusions and some have even shown beneficial effects of preischemic glucose infusions both in vitro (53)(54)(55)(56) and in vivo (21, 22, 31-33, 57, 58).…”

“…Several studies have demonstrated that hyperglycemia in conjunction with hypoxic/ischemic episodes in piglets accentuates the decreases in brain pH, increases in the production of lactate and lipid peroxidation products, and increases pathologic damage (27)(28)(29). In exteriorized asphyxiated fetal sheep, hyperglycemia was associated with reduced cerebral oxygen consumption and deterioration of the somatosensory evoked potentials (24) and in the newborn dog, hyperglycemia accentuated brain damage in select brain regions (30).…”

Neurochemical disorders at the hypoxic-ischemic encephalopathy in newborns

“…Для поддержания мозгового кровотока происходит перераспределение гемодинамики с увеличением кровоснабжения сердца и головного мозга за счет подъема АД вследствие повышенного выброса адреналина и норадреналина (катехоламиновый всплеск) [5][6]. Глюкоза и кислород являются основными субстратами питания мозга.…”