Role of tissue lactate and substrate availability in 1,3-butanediol-enhanced hypoxic survival in the mouse

Jeffrey Kirsch, L. G. D’Alecy

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Previously we found that 1,3-butanediol-treated mice live longer during hypoxia. We hypothesized that 1,3-butanediol could reduce the brain’s accumulation of potentially cytotoxic lactate and/or elevate brain substrate availability (ketones or glucose) and thus maintain the brain’s energy producing capability even during reduced oxygen availability. To test these hypotheses, whole brain metabolites from normoxic and hypoxic mice, pretreated with 1,3-butanediol or insulin, were compared to saline controls. During hypoxia both pretreated groups had lower brain lactate than controls. If lactate accumulation was the sole factor responsible for hypoxic tolerance, insulin should have increased brain lactate since insulin has been shown previously to reduce hypoxic tolerance. In normoxic mice the ratio of lactate to pyruvate and the level of malate and fumarate were not changed by 1,3-butanediol as is found with other agents known to protect the hypoxic animal. When substrate availability was directly elevated by beta-hydroxybutyrate and glucose administration hypoxic survival time increased thus implicating substrate availability as an important factor in hypoxic tolerance. We conclude that reduced brain lactate and augmented substrate availability both contribute to 1,3-butanediol-enhanced hypoxic tolerance in this animal model.

Original languageEnglish (US)
Pages (from-to)971-976
Number of pages6
JournalStroke
Volume14
Issue number6
StatePublished - 1983
Externally publishedYes

Fingerprint

Lactic Acid
Brain
Insulin
Glucose
Fumarates
3-Hydroxybutyric Acid
1,3-butylene glycol
Ketones
Pyruvic Acid
Animal Models
Oxygen

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Neuroscience(all)

Cite this

Role of tissue lactate and substrate availability in 1,3-butanediol-enhanced hypoxic survival in the mouse. / Kirsch, Jeffrey; D’Alecy, L. G.

In: Stroke, Vol. 14, No. 6, 1983, p. 971-976.

Research output: Contribution to journalArticle

@article{48c4109bc52d420ea140382356f8d974,
title = "Role of tissue lactate and substrate availability in 1,3-butanediol-enhanced hypoxic survival in the mouse",
abstract = "Previously we found that 1,3-butanediol-treated mice live longer during hypoxia. We hypothesized that 1,3-butanediol could reduce the brain’s accumulation of potentially cytotoxic lactate and/or elevate brain substrate availability (ketones or glucose) and thus maintain the brain’s energy producing capability even during reduced oxygen availability. To test these hypotheses, whole brain metabolites from normoxic and hypoxic mice, pretreated with 1,3-butanediol or insulin, were compared to saline controls. During hypoxia both pretreated groups had lower brain lactate than controls. If lactate accumulation was the sole factor responsible for hypoxic tolerance, insulin should have increased brain lactate since insulin has been shown previously to reduce hypoxic tolerance. In normoxic mice the ratio of lactate to pyruvate and the level of malate and fumarate were not changed by 1,3-butanediol as is found with other agents known to protect the hypoxic animal. When substrate availability was directly elevated by beta-hydroxybutyrate and glucose administration hypoxic survival time increased thus implicating substrate availability as an important factor in hypoxic tolerance. We conclude that reduced brain lactate and augmented substrate availability both contribute to 1,3-butanediol-enhanced hypoxic tolerance in this animal model.",
author = "Jeffrey Kirsch and D’Alecy, {L. G.}",
year = "1983",
language = "English (US)",
volume = "14",
pages = "971--976",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Role of tissue lactate and substrate availability in 1,3-butanediol-enhanced hypoxic survival in the mouse

AU - Kirsch, Jeffrey

AU - D’Alecy, L. G.

PY - 1983

Y1 - 1983

N2 - Previously we found that 1,3-butanediol-treated mice live longer during hypoxia. We hypothesized that 1,3-butanediol could reduce the brain’s accumulation of potentially cytotoxic lactate and/or elevate brain substrate availability (ketones or glucose) and thus maintain the brain’s energy producing capability even during reduced oxygen availability. To test these hypotheses, whole brain metabolites from normoxic and hypoxic mice, pretreated with 1,3-butanediol or insulin, were compared to saline controls. During hypoxia both pretreated groups had lower brain lactate than controls. If lactate accumulation was the sole factor responsible for hypoxic tolerance, insulin should have increased brain lactate since insulin has been shown previously to reduce hypoxic tolerance. In normoxic mice the ratio of lactate to pyruvate and the level of malate and fumarate were not changed by 1,3-butanediol as is found with other agents known to protect the hypoxic animal. When substrate availability was directly elevated by beta-hydroxybutyrate and glucose administration hypoxic survival time increased thus implicating substrate availability as an important factor in hypoxic tolerance. We conclude that reduced brain lactate and augmented substrate availability both contribute to 1,3-butanediol-enhanced hypoxic tolerance in this animal model.

AB - Previously we found that 1,3-butanediol-treated mice live longer during hypoxia. We hypothesized that 1,3-butanediol could reduce the brain’s accumulation of potentially cytotoxic lactate and/or elevate brain substrate availability (ketones or glucose) and thus maintain the brain’s energy producing capability even during reduced oxygen availability. To test these hypotheses, whole brain metabolites from normoxic and hypoxic mice, pretreated with 1,3-butanediol or insulin, were compared to saline controls. During hypoxia both pretreated groups had lower brain lactate than controls. If lactate accumulation was the sole factor responsible for hypoxic tolerance, insulin should have increased brain lactate since insulin has been shown previously to reduce hypoxic tolerance. In normoxic mice the ratio of lactate to pyruvate and the level of malate and fumarate were not changed by 1,3-butanediol as is found with other agents known to protect the hypoxic animal. When substrate availability was directly elevated by beta-hydroxybutyrate and glucose administration hypoxic survival time increased thus implicating substrate availability as an important factor in hypoxic tolerance. We conclude that reduced brain lactate and augmented substrate availability both contribute to 1,3-butanediol-enhanced hypoxic tolerance in this animal model.

UR - http://www.scopus.com/inward/record.url?scp=0021016386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021016386&partnerID=8YFLogxK

M3 - Article

VL - 14

SP - 971

EP - 976

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 6

ER -