title: Intermittent pacing therapy favorably modulates infarct remodeling.
abstract: Despite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown. We therefore investigated the effects of IPT on global LV remodeling and infarct geometry in swine with a 3-day old AMI. For this purpose, fifteen pigs underwent 2 h ligation of the left circumflex coronary artery followed by reperfusion. An epicardial pacing lead was implanted in the peri-infarct zone. After three days, global LV remodeling and infarct geometry were assessed using magnetic resonance imaging (MRI). Animals were stratified into MI control and IPT groups. Thirty-five days post-AMI, follow-up MRI was obtained and myofibroblast content, markers of extracellular matrix (ECM) turnover and Wnt/frizzled signaling in infarct and non-infarct control tissue were studied. Results showed that IPT had no significant effect on global LV remodeling, function or infarct mass, but modulated infarct healing. In MI control pigs, infarct mass reduction was principally due to a 26.2 ± 4.4% reduction in infarct thickness (P ≤ 0.05), whereas in IPT pigs it was mainly due to a 35.7 ± 4.5% decrease in the number of infarct segments (P ≤ 0.05), with no significant change in infarct thickness. Myofibroblast content of the infarct zone was higher in IPT (10.9 ± 2.1%) compared to MI control (5.4 ± 1.6%; P ≤ 0.05). Higher myofibroblast presence did not coincide with alterations in expression of genes involved in ECM turnover or Wnt/frizzled signaling at 5 weeks follow-up. Taken together, IPT limited infarct expansion and altered infarct composition, showing that IPT influences remodeling of the infarct zone, likely by increasing regional myofibroblast content.
authors.affiliation: Department of Cardiology, Ee-2351, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: André
authors.initials: A
authors.lastname: Uitterdijk
authors.affiliation: Department of Cardiology, Ee-2351, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.|Department of Radiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Tirza
authors.initials: T
authors.lastname: Springeling
authors.affiliation: Department of Pharmacology, CARIM, Maastricht University, Maastricht, The Netherlands.
authors.forename: Kevin C M
authors.initials: KCM
authors.lastname: Hermans
authors.affiliation: Department of Cardiology, Ee-2351, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Daphne
authors.initials: D
authors.lastname: Merkus
authors.affiliation: Department of Cardiology, Ee-2351, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: de Beer
authors.affiliation: Department of Cardiology, Ee-2351, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gorsse-Bakker
authors.affiliation: Boston Scientific Corporation, St. Paul, MN, USA.|Medical Products Division, W.L. Gore and Associates, Flagstaff, AZ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Mokelke
authors.affiliation: Department of Pharmacology, CARIM, Maastricht University, Maastricht, The Netherlands.
authors.forename: Evangelos P
authors.initials: EP
authors.lastname: Daskalopoulos
authors.affiliation: Department of Radiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Piotr A
authors.initials: PA
authors.lastname: Wielopolski
authors.affiliation: Department of Pathology, CARIM, Maastricht University, Maastricht, The Netherlands.
authors.forename: Jack P M
authors.initials: JPM
authors.lastname: Cleutjens
authors.affiliation: Department of Pharmacology, CARIM, Maastricht University, Maastricht, The Netherlands.
authors.forename: W Matthijs
authors.initials: WM
authors.lastname: Blankesteijn
authors.affiliation: Department of Physiology, CARIM, Maastricht University, Maastricht, The Netherlands.
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
authors.affiliation: Department of Cardiology, Ee-2351, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van der Giessen
authors.affiliation: Department of Cardiology, Ee-2351, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.|Department of Radiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Robert-Jan M
authors.initials: RM
authors.lastname: van Geuns
authors.affiliation: Department of Cardiology, Ee-2351, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. d.duncker@erasmusmc.nl.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D013552:Swine; D020257:Ventricular Remodeling
keywords: Infarct expansion; Infarct geometry; Infarct healing; Myocardial infarction; Myofibroblasts; Swine