Comparison of Arrhythmogenicity and Proinflammatory Activity Induced by Intramyocardial or Epicardial Myoblast Sheet Delivery in a Rat Model of Ischemic Heart Failure

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dc.contributor.author Pätilä , Tommi
dc.contributor.author Miyagawa, Shigeru
dc.contributor.author Imanishi, Yukiko
dc.contributor.author Fukushima, Satsuki
dc.contributor.author Siltanen, Antti
dc.contributor.author Mervaala, Eero
dc.contributor.author Kankuri, Esko
dc.contributor.author Harjula, Ari
dc.contributor.author Sawa, Yoshiki
dc.date.accessioned 2015-10-06T11:05:03Z
dc.date.available 2015-10-06T11:05:03Z
dc.date.issued 2015-04-10
dc.identifier.citation Pätilä , T , Miyagawa , S , Imanishi , Y , Fukushima , S , Siltanen , A , Mervaala , E , Kankuri , E , Harjula , A & Sawa , Y 2015 , ' Comparison of Arrhythmogenicity and Proinflammatory Activity Induced by Intramyocardial or Epicardial Myoblast Sheet Delivery in a Rat Model of Ischemic Heart Failure ' , PLoS One , vol. 10 , no. 4 , 0123963 . https://doi.org/10.1371/journal.pone.0123963
dc.identifier.other PURE: 48854587
dc.identifier.other PURE UUID: ffcae557-92dd-4b02-84a9-c34211df20bd
dc.identifier.other WOS: 000352590300125
dc.identifier.other Scopus: 84928920372
dc.identifier.uri http://hdl.handle.net/10138/157018
dc.description.abstract Although cell therapy of the failing heart by intramyocardial injections of myoblasts to results in regenerative benefit, it has also been associated with undesired and prospectively fatal arrhythmias. We hypothesized that intramyocardial injections of myoblasts could enhance inflammatory reactivity and facilitate electrical cardiac abnormalities that can be reduced by epicardial myoblast sheet delivery. In a rat model of ischemic heart failure, myoblast therapy either by intramyocardial injections or epicardial cell sheets was given 2 weeks after occlusion of the coronary artery. Ventricular premature contractions (VPCs) were assessed, using an implanted three-lead electrocardiograph at 1, 7, and 14 days after therapy, and 16-point epicardial electropotential mapping (EEPM) was used to evaluate ventricular arrhythmogenicity under isoproterenol stress. Cardiac functioning was assessed by echocardiography. Both transplantation groups showed therapeutic benefit over sham therapy. However, VPCs were more frequent in the Injection group on day 1 and day 14 after therapy than in animals receiving epicardial or sham therapy (p <0.05 and p <0.01, respectively). EEPM under isoproterenol stress showed macroreentry at the infarct border area, leading to ventricular tachycardias in the Injection group, but not in the myoblast sheet- or sham-treated groups (p = 0.045). Both transplantation types modified the myocardial cytokine expression profile. In animals receiving epicardial myoblast therapy, selective reductions in the expressions of interferon gamma, interleukin (IL)-1 beta and IL12 were observed, accompanied by reduced infiltration of inflammatory CD11b- and CD68-positive leukocytes, compared with animals receiving myoblasts as intramyocardial injections. Intramyocardial myoblast delivery was associated with enhanced inflammatory and immunomodulatory reactivity and increased frequency of VPCs. In comparison to intramyocardial injection, the epicardial route may serve as the preferred method of skeletal myoblast transplantation to treat heart failure. en
dc.format.extent 15
dc.language.iso eng
dc.relation.ispartof PLoS One
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject MYOCARDIAL-INFARCTION
dc.subject CULTURED CARDIOMYOCYTES
dc.subject VENTRICULAR-ARRHYTHMIAS
dc.subject CELL THERAPY
dc.subject FOLLOW-UP
dc.subject TRANSPLANTATION
dc.subject INTERLEUKIN-1-BETA
dc.subject REPAIR
dc.subject PHASE
dc.subject IMPLANTATION
dc.subject 3126 Surgery, anesthesiology, intensive care, radiology
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title Comparison of Arrhythmogenicity and Proinflammatory Activity Induced by Intramyocardial or Epicardial Myoblast Sheet Delivery in a Rat Model of Ischemic Heart Failure en
dc.type Article
dc.contributor.organization Clinicum
dc.contributor.organization Lastenkirurgian yksikkö
dc.contributor.organization Children's Hospital
dc.contributor.organization Medicum
dc.contributor.organization Department of Pharmacology
dc.contributor.organization III kirurgian klinikka
dc.contributor.organization Department of Surgery
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1371/journal.pone.0123963
dc.relation.issn 1932-6203
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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