THE EFFECT OF HYPERCAPNIA UPON INTRACELLULAR pH IN THE BRAIN, EVALUATED BY THE BICARBONATE‐ CARBONIC ACID METHOD AND FROM THE CREATINE PHOSPHOKINASE EQUILIBRIUM

Section: Discussionsupporting

confidence: 87%

Brain pH in Focal Cerebral Ischemia and the Protective Effects of Barbiturate Anesthesia

Anderson

Sundt

1983

“…During halothane anesthesia, hypercarbia caused no significant de crease in the calculated value of ADP. This agrees with the result of Siesjo et al (1972), despite the fundamental difference in technique and the fact that NMR spectroscopy measures only the un bound fraction of the total ADP. During isoflurane anesthesia and no anesthesia, hypercarbia caused the calculated value of ADP to drop by �60%, which is a decrease close to that seen during super carbia.…”

Section: Resultssupporting

confidence: 80%

“…400 mm Hg) to study cerebral metabolic changes in vivo in rats (Litt et ai., 1985), and have shown that (a) ATP also remains unchanged during this more severe insult; (b) pHi decreases by the expected amount of �0.65 pH unit; and (c) there is complete neurologic recovery after normocarbia is restored. However, in our supercarbia study we observed a decrease in PCr of only =25%, which contrasts with the =40% decrease in PCr that was seen by Siesjo et al (1972) during hypercarbia. The mea sured forward and reverse fluxes for creatine kinase reaction, PCr + ADP + H+ � Cr + AT P, indicate that this reaction is close to equilibrium in brain and in muscle (Meyer et ai., 1982; Shoubridge et aI., 1982;Alger and Shulman, 1984).…”

contrasting

confidence: 53%

Cerebral Intracellular ADP Concentrations during Hypercarbia: An in vivo³¹P Nuclear Magnetic Resonance Study in Rats

Litt

González‐Méndez

Severinghaus

et al. 1986

Summary: Qualitatively different responses of ADP levels have previously been observed in the brain during hypercarbia, One investigation has found that cerebral ADP stayed constant during hypercarbia in rats that were anesthetized with halothane, while another observed that ADP decreased during supercarbia in rats that received no supplemental anesthesia, This article reports an in vivo 31p nuclear magnetic resonance study to test the hy pothesis that halothane anesthesia accounts for the dis crepant observations, lsoflurane anesthesia was also studied in a second group of rats to see if a different gen eral anesthetic agent would cause the same effects that halothane causes, The two groups of five rats underwent dual episodes of hypercarbia that were separated by a 45-min recovery period, General anesthesia, either 0,5% HYPERCARBIA, BRAIN ENERGY METABOLISM, AND ANESTHESIAThe cerebral metabolic response of oxygenated rats to acute hypercarbia (P aco2 = 250 mm Hg) has been studied with invasive biochemical techniques (Siesjo et ai., 1972) and noninvasive 31 P nuclear magnetic resonance (NMR) methodologies (Nioka et ai., 1984; Petroff et ai., 1984), Siesjo et aI. (1972) found that (a) brain tissue ATP and ADP remained unchanged up to arterial CO2 tensions of =260 mm Hg; (b) the creatine kinase equilibrium equation completely accounts for the observed decrease in phosphocreatine (PCr) with intracellular pH (pH); Received October 11,1985; accepted December 12, 1985. Address correspondence and reprint requests to Dr. L. Litt at Anesthesia Department, UCSF-S436, San Francisco, CA 94143, U,S.A.Abbreviations used: NMR, nuclear magnetic resonance; PCr, phosphocreatine; pHi' intracellular pH, 389 halothane or 1.0% isoflurane, was administered during the first episode but not during the second, Hypercarbia during halothane anesthesia caused the measured phos phocreatine (PCr) to decrease by 40%, while the calcu lated change in ADP was 10%, in agreement with the former investigation, In contrast, hypercarbia during ei ther isoflurane anesthesia or no anesthesia caused a de crease of only 10% in PCr, which meant that the calcu lated decrease in ADP was 60%, in agreement with the results of the second investigation, We conclude that during hypercarbia, clinical concentrations of halothane, unlike clinical concentrations of isoflurane, interfere with the regulation of ATP metabolism, Key Words: Bioener getics-Brain-Halothane-Hypercarbia-In vivo Isoflurane-Nuclear magnetic resonance-Supercarbia, and (c) hypercarbia is an anesthetic state that occurs without energy failure. We recently used 31p NMR spectroscopy during supercarbia (Paco2 ? 400 mm Hg) to study cerebral metabolic changes in vivo in rats (Litt et ai., 1985), and have shown that (a) ATP also remains unchanged during this more severe insult; (b) pHi decreases by the expected amount of �0.65 pH unit; and (c) there is complete neurologic recovery after normocarbia is restored. However, in our supercarbia study we observed a decrease in PCr of only =25%, which contr...

“…The supernatant was neutralized with KOH. Lactate levels were determined by a standard en zymatic assay (Folbergrova et at., 1972).…”

Section: Lactate Measurementsmentioning

confidence: 99%

Extracellular pH Changes during Spreading Depression and Cerebral Ischemia: Mechanisms of Brain pH Regulation

Mutch

Hansen

1984

298

184

Summary:We have examined the extracellular pH (pH e) during spreading depression and complete cerebral isch emia in rat parietal cortex utilizing double-barrelled H + liquid ion exchanger microelectrodes. The baseline pHe of the parietal cortex was 7.33 at a mean arterial Peoz of 38 mm Hg. Following spreading depression and cerebral ischemia, highly reproducible triphasic changes in pHe occurred, which were intimately related to the negative deflection in tissue potential (Ye). The changes in pHe for spreading depression (n = 23) were a small initial acidic shift, beginning before the rapid change in Ye, followed by a rapid transient alkaline shift of 0.16 pH units, the onset of which coincided with the negative deflection in Ye• A prolonged acidic shift of 0.42 pH units then oc curred. The maximal decrease in pHe was to 6.97 and the mean duration of the triphasic pHe change was 7.8 min. The lactate concentration in brain cortex increased fromThe adaptive response by the brain microenvi ronment to altered extracellular pH (pHe) remains poorly understood, partially due to the difficulty in directly measuring the interstitial hydrogen ion con centration. Now, however, high-fidelity recordings of pH changes in mammalian brain interstitium can be obtained with double-barrelled H+ liquid ion ex changer (LIX) microelectrodes (Ammann et aI., 1981; Kraig et aI., 1983). The use of similar LIX microelectrodes has greatly facilitated study of Dr. Mutch's present address is Department of Anesthesia, St. Boniface General Hospital, 40 9 Ta che Avenue, Winnipeg, Man itoba, Canada R2H 2A6.Address correspondence and reprint requests to Dr. Hansen at Department of Medical Physiology A, University of Copen hagen, The Panum Institute, B1egdamsvej 3, DK-22 00, Copen hagen N, Denmark.Abbreviations used: DIDS, 4,4'-Diisothiocyanostilbene-2,2' disulfonic acid; DNDS, 4, 4' -dinitrostilbene-2,2' -disulfonic acid; EH+, potential derived from H+ activity; LlX, liquid ion ex changer; pHe, extracellular pH; Ve, tissue potential. 17 baseline 1.2 mM to 7.0 mM (n = 6) during the maximal acidic change in spreading depression. In addition, lactate levels correlated well with resolution of the pHe changes during spreading depression. The triphasic pHe changes following complete cerebral ischemia were an initial acidic shift of 0.43 pH units which developed over 2 min, then an alkaline shift of 0.10 pH units coincident with the negative deflection in Ye, and a final acidic shift of 0.26 pH units. The terminal pHe was 6.75. Superfusion of the cortex with inhibitors of carbonic anhydrase (acetazol amide), Na+/H+ counter transport (amiloride), and Cl-/ HC03' countertransport (4,4' -diisothiocyanostilbene-2,2' disulfonic acid) altered the triphasic pHe changes in a similar fashion for both spreading depression and cerebral ischemia, providing insights into the pHe regulatory mechanisms in mammalian brain.