Modulating cardiac conduction during metabolic ischemia with perfusate sodium and calcium in guinea pig hearts

Research output: Contribution to journalJournal articleResearchpeer-review

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Modulating cardiac conduction during metabolic ischemia with perfusate sodium and calcium in guinea pig hearts. / George, Sharon A; Hoeker, Gregory; Calhoun, Patrick J; Entz, Michael; Raisch, Tristan B; King, D Ryan; Khan, Momina; Baker, Chandra; Gourdie, Robert G; Smyth, James W; Nielsen, Morten S; Poelzing, Steven.

In: American Journal of Physiology: Heart and Circulatory Physiology, Vol. 316, No. 4, 01.02.2019, p. H849-H861.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

George, SA, Hoeker, G, Calhoun, PJ, Entz, M, Raisch, TB, King, DR, Khan, M, Baker, C, Gourdie, RG, Smyth, JW, Nielsen, MS & Poelzing, S 2019, 'Modulating cardiac conduction during metabolic ischemia with perfusate sodium and calcium in guinea pig hearts', American Journal of Physiology: Heart and Circulatory Physiology, vol. 316, no. 4, pp. H849-H861. https://doi.org/10.1152/ajpheart.00083.2018

APA

George, S. A., Hoeker, G., Calhoun, P. J., Entz, M., Raisch, T. B., King, D. R., ... Poelzing, S. (2019). Modulating cardiac conduction during metabolic ischemia with perfusate sodium and calcium in guinea pig hearts. American Journal of Physiology: Heart and Circulatory Physiology, 316(4), H849-H861. https://doi.org/10.1152/ajpheart.00083.2018

Vancouver

George SA, Hoeker G, Calhoun PJ, Entz M, Raisch TB, King DR et al. Modulating cardiac conduction during metabolic ischemia with perfusate sodium and calcium in guinea pig hearts. American Journal of Physiology: Heart and Circulatory Physiology. 2019 Feb 1;316(4):H849-H861. https://doi.org/10.1152/ajpheart.00083.2018

Author

George, Sharon A ; Hoeker, Gregory ; Calhoun, Patrick J ; Entz, Michael ; Raisch, Tristan B ; King, D Ryan ; Khan, Momina ; Baker, Chandra ; Gourdie, Robert G ; Smyth, James W ; Nielsen, Morten S ; Poelzing, Steven. / Modulating cardiac conduction during metabolic ischemia with perfusate sodium and calcium in guinea pig hearts. In: American Journal of Physiology: Heart and Circulatory Physiology. 2019 ; Vol. 316, No. 4. pp. H849-H861.

Bibtex

@article{1a6fd5f824fa4d548d6e962d7fb3fff7,
title = "Modulating cardiac conduction during metabolic ischemia with perfusate sodium and calcium in guinea pig hearts",
abstract = "We previously demonstrated that altering extracellular sodium (Nao) and calcium (Cao) can modulate a form of electrical communication between cardiomyocytes termed {"}ephaptic coupling{"} (EpC), especially during loss of gap junction coupling. We hypothesized that altering Nao and Cao modulates conduction velocity (CV) and arrhythmic burden during ischemia. Electrophysiology was quantified by optically mapping Langendorff-perfused guinea pig ventricles with modified Nao (147 or 155 mM) and Cao (1.25 or 2.0 mM) during 30 min of simulated metabolic ischemia (pH 6.5, anoxia, aglycemia). Gap junction-adjacent perinexal width ( WP), a candidate cardiac ephapse, and connexin (Cx)43 protein expression and Cx43 phosphorylation at S368 were quantified by transmission electron microscopy and Western immunoblot analysis, respectively. Metabolic ischemia slowed CV in hearts perfused with 147 mM Nao and 2.0 mM Cao; however, theoretically increasing EpC with 155 mM Nao was arrhythmogenic, and CV could not be measured. Reducing Cao to 1.25 mM expanded WP, as expected during ischemia, consistent with reduced EpC, but attenuated CV slowing while delaying arrhythmia onset. These results were further supported by osmotically reducing WP with albumin, which exacerbated CV slowing and increased early arrhythmias during ischemia, whereas mannitol expanded WP, permitted conduction, and delayed the onset of arrhythmias. Cx43 expression patterns during the various interventions insufficiently correlated with observed CV changes and arrhythmic burden. In conclusion, decreasing perfusate calcium during metabolic ischemia enhances perinexal expansion, attenuates conduction slowing, and delays arrhythmias. Thus, perinexal expansion may be cardioprotective during metabolic ischemia. NEW & NOTEWORTHY This study demonstrates, for the first time, that modulating perfusate ion composition can alter cardiac electrophysiology during simulated metabolic ischemia.",
author = "George, {Sharon A} and Gregory Hoeker and Calhoun, {Patrick J} and Michael Entz and Raisch, {Tristan B} and King, {D Ryan} and Momina Khan and Chandra Baker and Gourdie, {Robert G} and Smyth, {James W} and Nielsen, {Morten S} and Steven Poelzing",
year = "2019",
month = "2",
day = "1",
doi = "10.1152/ajpheart.00083.2018",
language = "English",
volume = "316",
pages = "H849--H861",
journal = "American Journal of Physiology: Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4",

}

RIS

TY - JOUR

T1 - Modulating cardiac conduction during metabolic ischemia with perfusate sodium and calcium in guinea pig hearts

AU - George, Sharon A

AU - Hoeker, Gregory

AU - Calhoun, Patrick J

AU - Entz, Michael

AU - Raisch, Tristan B

AU - King, D Ryan

AU - Khan, Momina

AU - Baker, Chandra

AU - Gourdie, Robert G

AU - Smyth, James W

AU - Nielsen, Morten S

AU - Poelzing, Steven

PY - 2019/2/1

Y1 - 2019/2/1

N2 - We previously demonstrated that altering extracellular sodium (Nao) and calcium (Cao) can modulate a form of electrical communication between cardiomyocytes termed "ephaptic coupling" (EpC), especially during loss of gap junction coupling. We hypothesized that altering Nao and Cao modulates conduction velocity (CV) and arrhythmic burden during ischemia. Electrophysiology was quantified by optically mapping Langendorff-perfused guinea pig ventricles with modified Nao (147 or 155 mM) and Cao (1.25 or 2.0 mM) during 30 min of simulated metabolic ischemia (pH 6.5, anoxia, aglycemia). Gap junction-adjacent perinexal width ( WP), a candidate cardiac ephapse, and connexin (Cx)43 protein expression and Cx43 phosphorylation at S368 were quantified by transmission electron microscopy and Western immunoblot analysis, respectively. Metabolic ischemia slowed CV in hearts perfused with 147 mM Nao and 2.0 mM Cao; however, theoretically increasing EpC with 155 mM Nao was arrhythmogenic, and CV could not be measured. Reducing Cao to 1.25 mM expanded WP, as expected during ischemia, consistent with reduced EpC, but attenuated CV slowing while delaying arrhythmia onset. These results were further supported by osmotically reducing WP with albumin, which exacerbated CV slowing and increased early arrhythmias during ischemia, whereas mannitol expanded WP, permitted conduction, and delayed the onset of arrhythmias. Cx43 expression patterns during the various interventions insufficiently correlated with observed CV changes and arrhythmic burden. In conclusion, decreasing perfusate calcium during metabolic ischemia enhances perinexal expansion, attenuates conduction slowing, and delays arrhythmias. Thus, perinexal expansion may be cardioprotective during metabolic ischemia. NEW & NOTEWORTHY This study demonstrates, for the first time, that modulating perfusate ion composition can alter cardiac electrophysiology during simulated metabolic ischemia.

AB - We previously demonstrated that altering extracellular sodium (Nao) and calcium (Cao) can modulate a form of electrical communication between cardiomyocytes termed "ephaptic coupling" (EpC), especially during loss of gap junction coupling. We hypothesized that altering Nao and Cao modulates conduction velocity (CV) and arrhythmic burden during ischemia. Electrophysiology was quantified by optically mapping Langendorff-perfused guinea pig ventricles with modified Nao (147 or 155 mM) and Cao (1.25 or 2.0 mM) during 30 min of simulated metabolic ischemia (pH 6.5, anoxia, aglycemia). Gap junction-adjacent perinexal width ( WP), a candidate cardiac ephapse, and connexin (Cx)43 protein expression and Cx43 phosphorylation at S368 were quantified by transmission electron microscopy and Western immunoblot analysis, respectively. Metabolic ischemia slowed CV in hearts perfused with 147 mM Nao and 2.0 mM Cao; however, theoretically increasing EpC with 155 mM Nao was arrhythmogenic, and CV could not be measured. Reducing Cao to 1.25 mM expanded WP, as expected during ischemia, consistent with reduced EpC, but attenuated CV slowing while delaying arrhythmia onset. These results were further supported by osmotically reducing WP with albumin, which exacerbated CV slowing and increased early arrhythmias during ischemia, whereas mannitol expanded WP, permitted conduction, and delayed the onset of arrhythmias. Cx43 expression patterns during the various interventions insufficiently correlated with observed CV changes and arrhythmic burden. In conclusion, decreasing perfusate calcium during metabolic ischemia enhances perinexal expansion, attenuates conduction slowing, and delays arrhythmias. Thus, perinexal expansion may be cardioprotective during metabolic ischemia. NEW & NOTEWORTHY This study demonstrates, for the first time, that modulating perfusate ion composition can alter cardiac electrophysiology during simulated metabolic ischemia.

U2 - 10.1152/ajpheart.00083.2018

DO - 10.1152/ajpheart.00083.2018

M3 - Journal article

C2 - 30707595

VL - 316

SP - H849-H861

JO - American Journal of Physiology: Heart and Circulatory Physiology

JF - American Journal of Physiology: Heart and Circulatory Physiology

SN - 0363-6135

IS - 4

ER -

ID: 216467049