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Modifications of Myofilament Structure and Function During Global Myocardial Ischemia

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dc.contributor.advisorEdward P Debold
dc.contributor.authorWoodward, Mike K
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.contributor.departmentMolecular & Cellular Biology
dc.date2024-03-28T20:01:54.000
dc.date.accessioned2024-04-26T18:20:40Z
dc.date.available2024-04-26T18:20:40Z
dc.date.submittedSeptember
dc.date.submitted2016
dc.description.abstractCardiac arrest is a prevalent condition with a poor prognosis, attributable in part to persistent myocardial dysfunction following resuscitation. The molecular basis of this dysfunction remains unclear. We induced cardiac arrest in a porcine model of acute sudden death and assessed the impact of ischemia and reperfusion on the molecular function of isolated cardiac contractile proteins. Cardiac arrest was electrically induced, left untreated for 12 min, and followed by a resuscitation protocol. With successful resuscitations, the heart was reperfused for 2 h (IR2) and the muscle harvested. In failed resuscitations, tissue samples were taken following the failed efforts (IDNR). Actin filament velocity, using myosin isolated from IR2 or IDNR cardiac tissue, was nearly identical to myosin from the control tissue in a motility assay. However, both maximal velocity (25% faster than control) and Ca2+ sensitivity (pCa50 6.57 ± 0.04 IDNR vs. 6.34 ± 0.07 control) were significantly (p < 0.05) enhanced using native thin filaments (actin, troponin, and tropomyosin) from IDNR samples, suggesting that the enhanced velocity is mediated through an alteration in muscle regulatory proteins (troponin and tropomyosin). Mass spectrometry analysis showed that only samples from the IR2 had an increase in total phosphorylation levels of troponin (Tn) and tropomyosin (Tm), but both IR2 and IDNR samples demonstrated a significant shift from mono-phosphorylated to bis-phosphorylated forms of the inhibitory subunit of Tn (TnI) compared to control. This suggests that the shift to bis-phosphorylation of TnI is associated with the enhanced function in IDNR, but this effect may be attenuated when phosphorylation of Tm is increased in tandem, as was observed for IR2. There are likely many other molecular changes induced following cardiac arrest, but to our knowledge, these data provide the first evidence that this form cardiac arrest can alter the in vitro function of the cardiac contractile proteins.
dc.description.degreeMaster of Science (M.S.)
dc.identifier.doihttps://doi.org/10.7275/8871409
dc.identifier.orcidN/A
dc.identifier.urihttps://hdl.handle.net/20.500.14394/33469
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1440&amp;context=masters_theses_2&amp;unstamped=1
dc.source.statuspublished
dc.subjectcardiac
dc.subjectischemia
dc.subjectreperfusion
dc.subjectin vitro
dc.subjectmotility
dc.subjectmodifications
dc.subjectCellular and Molecular Physiology
dc.subjectMolecular Biology
dc.subjectOther Biochemistry, Biophysics, and Structural Biology
dc.subjectStructural Biology
dc.titleModifications of Myofilament Structure and Function During Global Myocardial Ischemia
dc.typeopenaccess
dc.typearticle
dc.typethesis
digcom.contributor.authorisAuthorOfPublication|email:mkwoodward551@gmail.com|institution:University of Massachusetts Amherst|Woodward, Mike K
digcom.identifiermasters_theses_2/453
digcom.identifier.contextkey8871409
digcom.identifier.submissionpathmasters_theses_2/453
dspace.entity.typePublication
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