Cerebral Intracellular Changes during Supercarbia: An in vivo ³¹P Nuclear Magnetic Resonance Study in Rats

Abstract

Summary: 31p nuclear magnetic resonance (NMR) spec troscopy was used noninvasively to measure in vivo changes in intracellular pH and intracellular phosphate metabolites in the brains of rats during supercarbia (P aco2 "" 400 mm Hg). Five intubated rats were mechanically ventilated with inspired gas mixtures containing 70% CO2 and 30% 02' Supercarbia in the rat was observed to cause a greater reduction in cerebral intracellular pH (pH) and increase in Peo2 than observed in other experiments with rats after 15 min of global ischemia. Complete neurologic and metabolic recovery was observed in these animals, de spite an average decrease in pHj of 0.63 ± 0.02 pH unit during supercarbia episodes that raised Paco2 to 490 ± 80 mm Hg. No change was observed in cerebral intra cellular ATP and only a 25% decrease was detected in phosphocreatine. The concentration of free cerebral in- SUPERCARBIA AND BRAIN ENERGY METABOLISMIschemia and hypoventilation in clinical situa tions can cause hypercarbia in brain cells. During these conditions, some cells usually will also suffer from inadequate oxygen availability. Deleterious consequences of hypercarbia are known to arise from secondary physiological phenomena such as seizures, sympathetic stimulation, and certain ef fects of acidosis, such as cardiac irritability and de creased oxygen availability due to a right shift of the hemoglobin dissociation curve (Nunn, 1977). Abbreviations used: Cr, creatine; NMR, nuclear magnetic res onance; PCr, phosphocreatine; pHa, arterial pH; pHi' cerebral intracellular pH; PME, phosphomonoesters. tracellular ADP, which can be calculated if one assumes that the creatine kinase reaction is in equilibrium, de creased to approximately one-third of its control value. The calculated threefold decrease in the concentration of free ADP and twofold increase in the cytosolic phos phorylation potential suggest that there is increased in tracellular oxygenation during supercarbia. Because a more than fourfold increase in intracellular hydrogen ion concentration was tolerated without apparent clinical in jury, we conclude that so long as adequate tissue oxy genation and perfusion are maintained, a severe decrease in intracellular pH need not induce or indicate brain in jury.

Fructose-1,6-Bisphosphate Protects Astrocytes from Hypoxic Damage

“…How ever, despite a mean pH of 6.92, we found no evi dence of damage in glc + FDP-treated cells, whereas glc-treated cultures (without FDP but with the same low pH) had abnormal appearances, lower protein concentrations, and high LDH contents in their medium. This suggests that pH per se does not always damage cells, which was also shown by the in vivo studies of Litt et al (1985). They showed that hypercarbia-induced brain intracellular pH of 6.45 did not damage the CNS of adult rats if the concentration of ATP in their brains remained nor mal.…”

Effects of Hyperglycemia on the Time Course of Changes in Energy Metabolism and pH during Global Cerebral Ischemia and Reperfusion in Rats: Correlation of1H and31P NMR Spectroscopy with Fatty Acid and Excitatory Amino Acid Levels

“…2. lar pH during occlusion is not exclusively respon sible for preventing recovery. One rat in group B, for example, recovered despite a pH as low as that seen in group C; moreover, nonischemic rats with experimental hypercarbia resulting in brain pH val ues of 6.5 measured by NMR also recovered meta bolically (Litt et al, 1985). More important are the extent and rate of pH decrease and lactate accumu lation during the first 10-20 min of reperfusion.…”

NMR Spectroscopic Investigation of the Recovery of Energy and Acid—Base Homeostasis in the Cat Brain after Prolonged Ischemia

“…The importance of acidosis in the etiology of ir reversible cell injury is weakened by the results ob tained from in vivo and in vitro studies. Litt et al (1985) lowered cerebral pHi by 0.63 units in rats ventilated with 70% CO 2 without producing appar-ent biochemical injury. Siemkowicz and Hansen (1981) exposed normo-and hyperglycemic rats to 10 min of global ischemia.…”