Metabolic Determinants of Electrical Failure in Ex-Vivo Canine Model of Cardiac Arrest: Evidence for the Protective Role of Inorganic Pyrophosphate

Junko Shibayama; Tyson G Taylor; Paul W Venable; Nathaniel L Rhodes; Ryan B Gil; Mark Warren; Adam R Wende; E. Dale Abel; James Cox; Kenneth W Spitzer; Alexey V Zaitsev

doi:10.1371/journal.pone.0057821

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Metabolic Determinants of Electrical Failure in Ex-Vivo Canine Model of Cardiac Arrest: Evidence for the Protective Role of Inorganic Pyrophosphate

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Metabolic Determinants of Electrical Failure in Ex-Vivo Canine Model of Cardiac Arrest: Evidence for the Protective Role of Inorganic Pyrophosphate

Junko Shibayama, Tyson G Taylor, Paul W Venable, Nathaniel L Rhodes, Ryan B Gil, Mark Warren, Adam R Wende, E. Dale Abel, James Cox, Kenneth W Spitzer, …

PloS one, Vol.8(3), pp.e57821-e57821

03/08/2013

DOI: 10.1371/journal.pone.0057821

PMCID: PMC3592894

PMID: 23520482

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Abstract

Rationale: Deterioration of ventricular fibrillation (VF) into asystole or severe bradycardia (electrical failure) heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown. Objective: To determine metabolic factors of early electrical failure in an ex-vivo canine model of cardiac arrest (VF+global ischemia). Methods and results: Metabolomic screening was performed in left ventricular biopsies collected before and after 0.3, 2, 5, 10 and 20 min of VF and global ischemia. Electrical activity was monitored via plunge needle electrodes and pseudo-ECG. Four out of nine hearts exhibited electrical failure at 10.1±0.9 min (early-asys), while 5/9 hearts maintained VF for at least 19.7 min (late-asys). As compared to late-asys, early-asys hearts had more ADP, less phosphocreatine, and higher levels of lactate at some time points during VF/ischemia (all comparisons p<0.05). Pre-ischemic samples from late-asys hearts contained ∼25 times more inorganic pyrophosphate (PPi) than early-asys hearts. A mechanistic role of PPi in cardioprotection was then tested by monitoring mitochondrial membrane potential (ΔΨ) during 20 min of simulated-demand ischemia using potentiometric probe TMRM in rabbit adult ventricular myocytes incubated with PPi versus control group. Untreated myocytes experienced significant loss of ΔΨ while in the PPi-treated myocytes ΔΨ was relatively maintained throughout 20 min of simulated-demand ischemia as compared to control (p<0.05). Conclusions: High tissue level of PPi may prevent ΔΨm loss and electrical failure at the early phase of ischemic stress. The link between the two protective effects may involve decreased rates of mitochondrial ATP hydrolysis and lactate accumulation.

Medicine

Biology

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Title: Subtitle: Metabolic Determinants of Electrical Failure in Ex-Vivo Canine Model of Cardiac Arrest: Evidence for the Protective Role of Inorganic Pyrophosphate
Creators: Junko Shibayama
Tyson G Taylor
Paul W Venable
Nathaniel L Rhodes
Ryan B Gil
Mark Warren
Adam R Wende
E. Dale Abel
James Cox
Kenneth W Spitzer
Alexey V Zaitsev
Resource Type: Journal article
Publication Details: PloS one, Vol.8(3), pp.e57821-e57821
DOI: 10.1371/journal.pone.0057821
PMID: 23520482
PMCID: PMC3592894
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; San Francisco, USA
Alternative title: Metabolic Determinants of Asystole
Language: English
Date published: 03/08/2013
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025290602771

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