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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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 . DOI: 10.1371/journal.pone.0123963

Title: Comparison of Arrhythmogenicity and Proinflammatory Activity Induced by Intramyocardial or Epicardial Myoblast Sheet Delivery in a Rat Model of Ischemic Heart Failure
Author: Pätilä, Tommi; Miyagawa, Shigeru; Imanishi, Yukiko; Fukushima, Satsuki; Siltanen, Antti; Mervaala, Eero; Kankuri, Esko; Harjula, Ari; Sawa, Yoshiki
Other contributor: University of Helsinki, III kirurgian klinikka
University of Helsinki, Department of Pharmacology
University of Helsinki, Department of Pharmacology
University of Helsinki, Department of Pharmacology
University of Helsinki, III kirurgian klinikka






Date: 2015-04-10
Language: eng
Number of pages: 15
Belongs to series: PLoS One
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0123963
URI: http://hdl.handle.net/10138/157018
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.
Subject: MYOCARDIAL-INFARCTION
CULTURED CARDIOMYOCYTES
VENTRICULAR-ARRHYTHMIAS
CELL THERAPY
FOLLOW-UP
TRANSPLANTATION
INTERLEUKIN-1-BETA
REPAIR
PHASE
IMPLANTATION
3126 Surgery, anesthesiology, intensive care, radiology
3121 Internal medicine
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