Surgical Application of ECM-Biomaterial Enhances Myocardial Recovery Following Myocardial Infarction

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atmire.migration.oldid4614
dc.contributor.advisorFedak, Paul W. M.
dc.contributor.authorMewhort, Holly E. M.
dc.contributor.committeememberGiles, Wayne
dc.contributor.committeememberDuff, Henry
dc.contributor.committeememberYong, Voon Wee
dc.date.accessioned2016-07-20T21:13:51Z
dc.date.available2016-07-20T21:13:51Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractIntroduction: Ongoing improvements in the management of coronary artery disease continue to reduce mortality following myocardial infarction (MI), however, as a consequence the incidence of ischemic heart failure is on the rise. Healthy extracellular matrix (ECM) provides important cues that regulate cell function and survival. Dysregulation of the ECM following MI leads to cardiac fibrosis, left ventricular (LV) dilatation and heart failure. Here we assess whether ECM biology can be leveraged as a therapy to enhance myocardial recovery following MI. Methods and Results: Epicardial Infarct Repair (EIR), a novel bio-surgical procedure where a healthy ECM-biomaterial (CorMatrix®-ECM®, CorMatrix Cardiovascular Inc., GA, USA) is surgically applied to the epicardial surface of the heart post-MI, was evaluated. In a small animal permanent coronary artery ligation model we demonstrate that animals treated with ECM-biomaterial have improved myocardial function and attenuated LV remodeling compared to shams (ejection fraction (EF): 40.5±7.4% vs. 28.7±13.1%, respectively; p<0.001; LV end diastolic volume (LVEDV): 298.0±63.5μL vs. 373.7±78.8μL, respectively; p<0.0001). In order to determine whether this was the result of recovery of the infarcted myocardium or enhanced compensation by the remote myocardium we employed a large animal preclinical ischemia-reperfusion model and evaluated regional cardiac function by MRI demonstrating functional recovery of the infarcted myocardial territory, specifically infarcted myocardium otherwise defined as non-viable with reperfusion alone (change in regional myocardial contraction at 6-weeks: reperfusion+EIR: 28.6±14.0% vs. reperfusion alone: 4.2±13.5% wall thickening; p<0.05). In order to determine whether these structural and functional improvements are the consequence of passive biomechanical restraint or an active bio-inductive mechanism we compared EIR with active ECM-biomaterial versus inactivated (gluteraldehyde-fixed) ECM-biomaterial using our small animal permanent coronary artery ligation model. Animals treated with active ECM-biomaterial demonstrate improved cardiac function and attenuated structural remodeling when compared to inactivated ECM-biomaterial treated animals (EF: 40.5±7.4% vs. 32.7±9.3 %, respectively; p<0.001; LVEDV: 298.0±63.5μL vs. 341.2±48.4 μL, respectively; p<0.0001) as well as evidence of an active bio-inductive mechanism involving vasculogenesis. Conclusion: EIR with ECM-biomaterial attenuates adverse structural remodeling and improves functional recovery following MI through a bio-inductive mechanism involving vasculogenesis, demonstrating that healthy ECM biology can be leveraged to successfully treat MI.en_US
dc.identifier.citationMewhort, H. E. (2016). Surgical Application of ECM-Biomaterial Enhances Myocardial Recovery Following Myocardial Infarction (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27942en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/27942
dc.identifier.urihttp://hdl.handle.net/11023/3145
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectMedicine and Surgery
dc.subject.classificationExtracellular Matrixen_US
dc.subject.classificationIschemic Heart Failureen_US
dc.subject.classificationVasculogenesisen_US
dc.subject.classificationCardiac Remodelingen_US
dc.subject.classificationCardiac Surgeryen_US
dc.titleSurgical Application of ECM-Biomaterial Enhances Myocardial Recovery Following Myocardial Infarction
dc.typedoctoral thesis
thesis.degree.disciplineCardiovascular & Respiratory Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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