Elevated perfusate [Na+] increases contractile dysfunction during ischemia and reperfusion

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dc.contributor.authorKing, D. Ryanen
dc.contributor.authorPadget, Rachel L.en
dc.contributor.authorPerry, Justin B.en
dc.contributor.authorHoeker, Gregory S.en
dc.contributor.authorSmyth, James W.en
dc.contributor.authorBrown, David A.en
dc.contributor.authorPoelzing, Stevenen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2021-01-29T15:24:05Zen
dc.date.available2021-01-29T15:24:05Zen
dc.date.issued2020-10-14en
dc.description.abstractRecent studies revealed that relatively small changes in perfusate sodium ([Na+](o)) composition significantly affect cardiac electrical conduction and stability in contraction arrested ex vivo Langendorff heart preparations before and during simulated ischemia. Additionally, [Na+](o) modulates cardiomyocyte contractility via a sodium-calcium exchanger (NCX) mediated pathway. It remains unknown, however, whether modest changes to [Na+](o) that promote electrophysiologic stability similarly improve mechanical function during baseline and ischemia-reperfusion conditions. The purpose of this study was to quantify cardiac mechanical function during ischemia-reperfusion with perfusates containing 145 or 155 mM Na+ in Langendorff perfused isolated rat heart preparations. Relative to 145 mM Na+, perfusion with 155 mM [Na+](o) decreased the amplitude of left-ventricular developed pressure (LVDP) at baseline and accelerated the onset of ischemic contracture. Inhibiting NCX with SEA0400 abolished LVDP depression caused by increasing [Na+](o) at baseline and reduced the time to peak ischemic contracture. Ischemia-reperfusion decreased LVDP in all hearts with return of intrinsic activity, and reperfusion with 155 mM [Na+](o) further depressed mechanical function. In summary, elevating [Na+](o) by as little as 10 mM can significantly modulate mechanical function under baseline conditions, as well as during ischemia and reperfusion. Importantly, clinical use of Normal Saline, which contains 155 mM [Na+](o), with cardiac ischemia may require further investigation.en
dc.description.notesThis study was supported by National Institutes of Health F31-HL147438 awarded to DRK, National Institutes of Health R01-HL132236 awarded to JWS, National Institutes of Health R01-HL123647 awarded to DAB, and National Institutes of Health R01-HL141855, R01-HL138003, R01-HL102298 awarded to SP.en
dc.description.sponsorshipNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01-HL141855, R01-HL138003, R01-HL102298, F31-HL147438, R01-HL132236, R01-HL123647]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-020-74069-xen
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.other17289en
dc.identifier.pmid33057157en
dc.identifier.urihttp://hdl.handle.net/10919/102130en
dc.identifier.volume10en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleElevated perfusate [Na+] increases contractile dysfunction during ischemia and reperfusionen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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Scholarly Works, Human Nutrition, Foods, and Exercise
Scholarly Works, Biological Sciences
Scholarly Works, Biomedical Engineering and Mechanics
Scholarly Works, Fralin Biomedical Research Institute at VTC
Scholarly Works, Virginia Tech Carilion School of Medicine (VTCSOM)