Nuclear magnetic resonance studies of cationic and energetic alterations with oxidant stress in the perfused heart: Modulation with pyruvate and lactate

S. Yanagida, C. S. Luo, M. Doyle, G. M. Pohost, Martin Pike

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The postischemic generation of oxygen-derived free radicals may contribute to myocardial reperfusion injury by affecting sarcolemmal ion transport. Recent evidence indicates that exposure to reactive oxygen intermediates induces rapid increases in myocardial cytosolic free Ca2+ (Ca2+(i)). The mechanism is undetermined but may involve disturbances in Na+ homeostasis. We tested this hypothesis by interleaving 23Na and 31P nuclear magnetic resonance (NMR) measurements and Na+(i) and high-energy phosphates in glucose-perfused rat hearts exposed to hydroxyl radicals generated from H2O2 and Fe3+. In separate experiments, K+(i) and Ca2+(i) were measured with 39K and 19F NMR, respectively. The hearts rapidly exhibited contracture. Threefold Na+(i) increases and substantial K+(i) depletion were observed. Glycolytic inhibition was indicated by rapid sugar phosphate accumulation and cellular energy depletion. Notably, however, severe functional and energetic deterioration and substantial elevation of Ca2+(i) occurred before substantial Na+(i) accumulation or K+(i) depletion was observed. Further experiments investigated the ability of pyruvate to scavenge H2O2 and to protect the myocardium from oxidant stress. Pyruvate (1 or 2.5 mmol/L) dramatically attenuated functional and energetic alterations and alterations in Na+(i) and K+(i), whereas acetate (2.5 mmol/L) offered no protection. Unlike pyruvate, lactate (5 mmol/L) has little or no capacity to scavenge H2O2 but has similar protective effects. In conclusion, pyruvate effectively protects against H2O2/Fe3+, largely by direct H2O2 scavenging. Protection with lactate may involve intracellular pyruvate augmentation. Without exogenous pyruvate or lactate, myocardial Na+ homeostasis can be substantially altered by oxidant stress, possibly via cellular energy depletion. Excess Na+(i) accumulation may, in turn, hasten metabolic and functional deterioration, but a causal link with the initial alterations in function or Ca2+(i) was not supported.

Original languageEnglish (US)
Pages (from-to)773-783
Number of pages11
JournalCirculation Research
Volume77
Issue number4
StatePublished - 1995
Externally publishedYes

Fingerprint

Pyruvic Acid
Oxidants
Lactic Acid
Magnetic Resonance Spectroscopy
Homeostasis
Sugar Phosphates
Oxygen
Myocardial Reperfusion Injury
Ion Transport
Contracture
Hydroxyl Radical
Free Radicals
Myocardium
Acetates
Phosphates
Glucose

Keywords

  • free radicals
  • high-energy phosphates
  • intracellular Na
  • nuclear magnetic resonance
  • pyruvate

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Nuclear magnetic resonance studies of cationic and energetic alterations with oxidant stress in the perfused heart : Modulation with pyruvate and lactate. / Yanagida, S.; Luo, C. S.; Doyle, M.; Pohost, G. M.; Pike, Martin.

In: Circulation Research, Vol. 77, No. 4, 1995, p. 773-783.

Research output: Contribution to journalArticle

@article{fb60402341ce4e21bfcd1d4c393a2a7c,
title = "Nuclear magnetic resonance studies of cationic and energetic alterations with oxidant stress in the perfused heart: Modulation with pyruvate and lactate",
abstract = "The postischemic generation of oxygen-derived free radicals may contribute to myocardial reperfusion injury by affecting sarcolemmal ion transport. Recent evidence indicates that exposure to reactive oxygen intermediates induces rapid increases in myocardial cytosolic free Ca2+ (Ca2+(i)). The mechanism is undetermined but may involve disturbances in Na+ homeostasis. We tested this hypothesis by interleaving 23Na and 31P nuclear magnetic resonance (NMR) measurements and Na+(i) and high-energy phosphates in glucose-perfused rat hearts exposed to hydroxyl radicals generated from H2O2 and Fe3+. In separate experiments, K+(i) and Ca2+(i) were measured with 39K and 19F NMR, respectively. The hearts rapidly exhibited contracture. Threefold Na+(i) increases and substantial K+(i) depletion were observed. Glycolytic inhibition was indicated by rapid sugar phosphate accumulation and cellular energy depletion. Notably, however, severe functional and energetic deterioration and substantial elevation of Ca2+(i) occurred before substantial Na+(i) accumulation or K+(i) depletion was observed. Further experiments investigated the ability of pyruvate to scavenge H2O2 and to protect the myocardium from oxidant stress. Pyruvate (1 or 2.5 mmol/L) dramatically attenuated functional and energetic alterations and alterations in Na+(i) and K+(i), whereas acetate (2.5 mmol/L) offered no protection. Unlike pyruvate, lactate (5 mmol/L) has little or no capacity to scavenge H2O2 but has similar protective effects. In conclusion, pyruvate effectively protects against H2O2/Fe3+, largely by direct H2O2 scavenging. Protection with lactate may involve intracellular pyruvate augmentation. Without exogenous pyruvate or lactate, myocardial Na+ homeostasis can be substantially altered by oxidant stress, possibly via cellular energy depletion. Excess Na+(i) accumulation may, in turn, hasten metabolic and functional deterioration, but a causal link with the initial alterations in function or Ca2+(i) was not supported.",
keywords = "free radicals, high-energy phosphates, intracellular Na, nuclear magnetic resonance, pyruvate",
author = "S. Yanagida and Luo, {C. S.} and M. Doyle and Pohost, {G. M.} and Martin Pike",
year = "1995",
language = "English (US)",
volume = "77",
pages = "773--783",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Nuclear magnetic resonance studies of cationic and energetic alterations with oxidant stress in the perfused heart

T2 - Modulation with pyruvate and lactate

AU - Yanagida, S.

AU - Luo, C. S.

AU - Doyle, M.

AU - Pohost, G. M.

AU - Pike, Martin

PY - 1995

Y1 - 1995

N2 - The postischemic generation of oxygen-derived free radicals may contribute to myocardial reperfusion injury by affecting sarcolemmal ion transport. Recent evidence indicates that exposure to reactive oxygen intermediates induces rapid increases in myocardial cytosolic free Ca2+ (Ca2+(i)). The mechanism is undetermined but may involve disturbances in Na+ homeostasis. We tested this hypothesis by interleaving 23Na and 31P nuclear magnetic resonance (NMR) measurements and Na+(i) and high-energy phosphates in glucose-perfused rat hearts exposed to hydroxyl radicals generated from H2O2 and Fe3+. In separate experiments, K+(i) and Ca2+(i) were measured with 39K and 19F NMR, respectively. The hearts rapidly exhibited contracture. Threefold Na+(i) increases and substantial K+(i) depletion were observed. Glycolytic inhibition was indicated by rapid sugar phosphate accumulation and cellular energy depletion. Notably, however, severe functional and energetic deterioration and substantial elevation of Ca2+(i) occurred before substantial Na+(i) accumulation or K+(i) depletion was observed. Further experiments investigated the ability of pyruvate to scavenge H2O2 and to protect the myocardium from oxidant stress. Pyruvate (1 or 2.5 mmol/L) dramatically attenuated functional and energetic alterations and alterations in Na+(i) and K+(i), whereas acetate (2.5 mmol/L) offered no protection. Unlike pyruvate, lactate (5 mmol/L) has little or no capacity to scavenge H2O2 but has similar protective effects. In conclusion, pyruvate effectively protects against H2O2/Fe3+, largely by direct H2O2 scavenging. Protection with lactate may involve intracellular pyruvate augmentation. Without exogenous pyruvate or lactate, myocardial Na+ homeostasis can be substantially altered by oxidant stress, possibly via cellular energy depletion. Excess Na+(i) accumulation may, in turn, hasten metabolic and functional deterioration, but a causal link with the initial alterations in function or Ca2+(i) was not supported.

AB - The postischemic generation of oxygen-derived free radicals may contribute to myocardial reperfusion injury by affecting sarcolemmal ion transport. Recent evidence indicates that exposure to reactive oxygen intermediates induces rapid increases in myocardial cytosolic free Ca2+ (Ca2+(i)). The mechanism is undetermined but may involve disturbances in Na+ homeostasis. We tested this hypothesis by interleaving 23Na and 31P nuclear magnetic resonance (NMR) measurements and Na+(i) and high-energy phosphates in glucose-perfused rat hearts exposed to hydroxyl radicals generated from H2O2 and Fe3+. In separate experiments, K+(i) and Ca2+(i) were measured with 39K and 19F NMR, respectively. The hearts rapidly exhibited contracture. Threefold Na+(i) increases and substantial K+(i) depletion were observed. Glycolytic inhibition was indicated by rapid sugar phosphate accumulation and cellular energy depletion. Notably, however, severe functional and energetic deterioration and substantial elevation of Ca2+(i) occurred before substantial Na+(i) accumulation or K+(i) depletion was observed. Further experiments investigated the ability of pyruvate to scavenge H2O2 and to protect the myocardium from oxidant stress. Pyruvate (1 or 2.5 mmol/L) dramatically attenuated functional and energetic alterations and alterations in Na+(i) and K+(i), whereas acetate (2.5 mmol/L) offered no protection. Unlike pyruvate, lactate (5 mmol/L) has little or no capacity to scavenge H2O2 but has similar protective effects. In conclusion, pyruvate effectively protects against H2O2/Fe3+, largely by direct H2O2 scavenging. Protection with lactate may involve intracellular pyruvate augmentation. Without exogenous pyruvate or lactate, myocardial Na+ homeostasis can be substantially altered by oxidant stress, possibly via cellular energy depletion. Excess Na+(i) accumulation may, in turn, hasten metabolic and functional deterioration, but a causal link with the initial alterations in function or Ca2+(i) was not supported.

KW - free radicals

KW - high-energy phosphates

KW - intracellular Na

KW - nuclear magnetic resonance

KW - pyruvate

UR - http://www.scopus.com/inward/record.url?scp=0029112854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029112854&partnerID=8YFLogxK

M3 - Article

C2 - 7554125

AN - SCOPUS:0029112854

VL - 77

SP - 773

EP - 783

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 4

ER -