Show simple item record

dc.creatorArteaga, GM
dc.creatorWarren, CM
dc.creatorMilutinović-Smiljanić, Sanja
dc.creatorMartin, AF
dc.creatorSolaro, RJ
dc.date.accessioned2020-07-02T12:08:20Z
dc.date.available2020-07-02T12:08:20Z
dc.date.issued2005
dc.identifier.issn0363-6135
dc.identifier.urihttp://smile.stomf.bg.ac.rs/handle/123456789/1249
dc.description.abstractAlteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function.en
dc.publisherAmer Physiological Soc, Bethesda
dc.relationNHLBI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [KO1-HL-67709, P01-HL-62426, R37-HL-22231]
dc.rightsrestrictedAccess
dc.sourceAmerican Journal of Physiology - Heart & Circulatory Physiology
dc.subjecttroponin Ien
dc.subjectcalcium sensitizersen
dc.subjectphosphorylationen
dc.subjectstunningen
dc.subjectcross bridge-dependent activationen
dc.titleSpecific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunctionen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractМартин, AФ; Милутиновић-Смиљанић, Сања; Соларо, РЈ; Wаррен, ЦМ; Aртеага, ГМ;
dc.citation.volume289
dc.citation.issue5
dc.citation.spageH2183
dc.citation.epageH2192
dc.citation.other289(5): H2183-H2192
dc.citation.rankM21
dc.identifier.wos000232497500052
dc.identifier.doi10.1152/ajpheart.00520.2005
dc.identifier.pmid16024565
dc.identifier.scopus2-s2.0-27144551306
dc.identifier.rcubconv_2695
dc.type.versionpublishedVersion


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record