Brain energetics and tolerance to anoxia in deep hypothermia

Radoslav K. Andjus, Željko Džakula, John L. Markley, Slobodan I Macura

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The remarkable time-resolution enhancement by deep lethargic hypothermia (15°C rectal temperature, "cold narcosis," "anesthesia by internal cold") of metabolic events in the rat brain after oxygen deprivation has been exploited to monitor metabolic changes by in vivo 31P-NMR. A correlation was established between the bioenergetic status of the brain and physiological descriptors of tolerance (survival and revival times) determined in parallel experiments with large series of animals. Spectral peak integrals were transformed into absolute concentrations by comparison to biochemically determined time series of data obtained in freeze-trapping experiments conducted under identical conditions. Serial spectra were used to reconstruct the time-course kinetics of intracellular brain pH and of concentration changes of inorganic phosphate, phosphocreatine, ATP, and ADP. Both the biochemical and NMR time series of data were simultaneously fitted by a set of exponential kinetic equations accounting for relationships imposed by the Lohmann and adenylate kinase reactions. Depletion profiles were then computed for a number of descriptors of brain energy status (energy charge, phosphorylation potential, total adenylate, and primary energy stores expressed as the sum of high-energy phosphate-bond equivalents). The results contribute to the understanding of the role of brain energetics in tolerance to oxygen deprivation.

Original languageEnglish (US)
Pages (from-to)10-35
Number of pages26
JournalAnnals of the New York Academy of Sciences
Volume1048
DOIs
StatePublished - 2005

Fingerprint

Hypothermia
Brain
Time series
Phosphates
Nuclear magnetic resonance
Oxygen
Stupor
Adenylate Kinase
Phosphorylation
Kinetics
Phosphocreatine
Adenosine Diphosphate
Energy Metabolism
Rats
Animals
Anesthesia
Adenosine Triphosphate
Experiments
Hypoxia
Tolerance

Keywords

  • Anoxia
  • Bioenergetics
  • Brain energetics
  • Hypothermia
  • In vivo NMR

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Brain energetics and tolerance to anoxia in deep hypothermia. / Andjus, Radoslav K.; Džakula, Željko; Markley, John L.; Macura, Slobodan I.

In: Annals of the New York Academy of Sciences, Vol. 1048, 2005, p. 10-35.

Research output: Contribution to journalArticle

Andjus, Radoslav K. ; Džakula, Željko ; Markley, John L. ; Macura, Slobodan I. / Brain energetics and tolerance to anoxia in deep hypothermia. In: Annals of the New York Academy of Sciences. 2005 ; Vol. 1048. pp. 10-35.
@article{a845f11c06e443f9b0350cb349326d7a,
title = "Brain energetics and tolerance to anoxia in deep hypothermia",
abstract = "The remarkable time-resolution enhancement by deep lethargic hypothermia (15°C rectal temperature, {"}cold narcosis,{"} {"}anesthesia by internal cold{"}) of metabolic events in the rat brain after oxygen deprivation has been exploited to monitor metabolic changes by in vivo 31P-NMR. A correlation was established between the bioenergetic status of the brain and physiological descriptors of tolerance (survival and revival times) determined in parallel experiments with large series of animals. Spectral peak integrals were transformed into absolute concentrations by comparison to biochemically determined time series of data obtained in freeze-trapping experiments conducted under identical conditions. Serial spectra were used to reconstruct the time-course kinetics of intracellular brain pH and of concentration changes of inorganic phosphate, phosphocreatine, ATP, and ADP. Both the biochemical and NMR time series of data were simultaneously fitted by a set of exponential kinetic equations accounting for relationships imposed by the Lohmann and adenylate kinase reactions. Depletion profiles were then computed for a number of descriptors of brain energy status (energy charge, phosphorylation potential, total adenylate, and primary energy stores expressed as the sum of high-energy phosphate-bond equivalents). The results contribute to the understanding of the role of brain energetics in tolerance to oxygen deprivation.",
keywords = "Anoxia, Bioenergetics, Brain energetics, Hypothermia, In vivo NMR",
author = "Andjus, {Radoslav K.} and Željko Džakula and Markley, {John L.} and Macura, {Slobodan I}",
year = "2005",
doi = "10.1196/annals.1342.003",
language = "English (US)",
volume = "1048",
pages = "10--35",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Brain energetics and tolerance to anoxia in deep hypothermia

AU - Andjus, Radoslav K.

AU - Džakula, Željko

AU - Markley, John L.

AU - Macura, Slobodan I

PY - 2005

Y1 - 2005

N2 - The remarkable time-resolution enhancement by deep lethargic hypothermia (15°C rectal temperature, "cold narcosis," "anesthesia by internal cold") of metabolic events in the rat brain after oxygen deprivation has been exploited to monitor metabolic changes by in vivo 31P-NMR. A correlation was established between the bioenergetic status of the brain and physiological descriptors of tolerance (survival and revival times) determined in parallel experiments with large series of animals. Spectral peak integrals were transformed into absolute concentrations by comparison to biochemically determined time series of data obtained in freeze-trapping experiments conducted under identical conditions. Serial spectra were used to reconstruct the time-course kinetics of intracellular brain pH and of concentration changes of inorganic phosphate, phosphocreatine, ATP, and ADP. Both the biochemical and NMR time series of data were simultaneously fitted by a set of exponential kinetic equations accounting for relationships imposed by the Lohmann and adenylate kinase reactions. Depletion profiles were then computed for a number of descriptors of brain energy status (energy charge, phosphorylation potential, total adenylate, and primary energy stores expressed as the sum of high-energy phosphate-bond equivalents). The results contribute to the understanding of the role of brain energetics in tolerance to oxygen deprivation.

AB - The remarkable time-resolution enhancement by deep lethargic hypothermia (15°C rectal temperature, "cold narcosis," "anesthesia by internal cold") of metabolic events in the rat brain after oxygen deprivation has been exploited to monitor metabolic changes by in vivo 31P-NMR. A correlation was established between the bioenergetic status of the brain and physiological descriptors of tolerance (survival and revival times) determined in parallel experiments with large series of animals. Spectral peak integrals were transformed into absolute concentrations by comparison to biochemically determined time series of data obtained in freeze-trapping experiments conducted under identical conditions. Serial spectra were used to reconstruct the time-course kinetics of intracellular brain pH and of concentration changes of inorganic phosphate, phosphocreatine, ATP, and ADP. Both the biochemical and NMR time series of data were simultaneously fitted by a set of exponential kinetic equations accounting for relationships imposed by the Lohmann and adenylate kinase reactions. Depletion profiles were then computed for a number of descriptors of brain energy status (energy charge, phosphorylation potential, total adenylate, and primary energy stores expressed as the sum of high-energy phosphate-bond equivalents). The results contribute to the understanding of the role of brain energetics in tolerance to oxygen deprivation.

KW - Anoxia

KW - Bioenergetics

KW - Brain energetics

KW - Hypothermia

KW - In vivo NMR

UR - http://www.scopus.com/inward/record.url?scp=25144491098&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=25144491098&partnerID=8YFLogxK

U2 - 10.1196/annals.1342.003

DO - 10.1196/annals.1342.003

M3 - Article

C2 - 16154918

AN - SCOPUS:25144491098

VL - 1048

SP - 10

EP - 35

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -