title: Rapid ventricular pacing induces delayed cardioprotection against myocardial stunning.
abstract: Tachycardia with rapid ventricular pacing induces delayed preconditioning against arrhythmias secondary to coronary artery occlusion (CAO) and reperfusion (CAR) but its effects on myocardial stunning remains unknown. Accordingly, we investigated whether delayed preconditioning with ventricular pacing develops against myocardial stunning and whether this phenomenon is triggered by reactive oxygen species. Eight chronically instrumented conscious dogs underwent three experimental sequences in a random order a week apart: (a) 10-min CAO (coronary occluder) followed by CAR, i.e. "Control" sequence; (b) pacing (right ventricular electrodes, 240 beats/min during 40 min) performed 24 h before the 10-min CAO, i.e. "PC" sequence; and (c) N-(2-mercaptopropionyl)-glycine (MPG, 100 mg/kg per h) administered concomitantly to pacing and 10-min CAO performed 24 h later, i.e. "PC+MPG" sequence. During "Control", left ventricular (LV) wall thickening (%, sonomicrometry) was dramatically reduced during CAO (-96 +/- 5% from 2.9 +/- 0.4 mm) and remained depressed during CAR demonstrating myocardial stunning. During "PC", LV wall thickening was not altered by pacing per se and was similarly decreased during CAO vs. "Control". However, during CAR, LV wall thickening was improved vs. "Control" (e.g. -24 +/- 5% and -8 +/- 4% from corresponding baseline for "PC" and "Control", respectively at 2 h-CAR; P<0.05), demonstrating delayed preconditioning. Administration of MPG during pacing (n=5) abolished the beneficial effects of pacing. Myocardial lactate extraction and transmural distribution of regional myocardial blood flow (fluorescent microspheres) were not modified, by pacing. In conclusion, tachycardia with rapid ventricular pacing induces delayed cardioprotection against myocardial stunning. The production of reactive oxygen species independently from ischemia appears to be a major trigger for this phenomenon.
authors.affiliation: Laboratoire de Pharmacologie, Inserm U 660, Faculté de Médecine de Créteil, Université Paris Val de Marne, 8, rue du Général Sarrail, 94000 Créteil, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lucats
authors.forename: Virginie
authors.initials: V
authors.lastname: Chalvignac
authors.forename: Alain
authors.initials: A
authors.lastname: Bizé
authors.forename: Xavier
authors.initials: X
authors.lastname: Monnet
authors.forename: Roland
authors.initials: R
authors.lastname: Zini
authors.forename: Luc
authors.initials: L
authors.lastname: Hittinger
authors.forename: Alain
authors.initials: A
authors.lastname: Berdeaux
authors.forename: Bijan
authors.initials: B
authors.lastname: Ghaleh
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D019157:Ischemic Preconditioning, Myocardial; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017180:Tachycardia, Ventricular / Q000378:metabolism*; D008625:Tiopronin / Q000008:administration & dosage
chemical_list: D017382:Reactive Oxygen Species; D008625:Tiopronin