title: Pacing-induced dyssynchrony during early reperfusion reduces infarct size.
abstract: OBJECTIVE
  Considering the recent discovery of postconditioning, we investigated whether intermittent dyssynchrony immediately upon reperfusion induces cardioprotection as well.
  
  
  BACKGROUND
  Intermittent dyssynchrony, induced by ventricular pacing, preconditions myocardium.
  
  
  METHODS
  Isolated ejecting rabbit hearts were subjected to 30-min coronary occlusion and 2-h reperfusion. Control, left ventricular (LV) pacing preconditioning (LVPpreC) (3 x 5-min LV pacing), and LV pacing postconditioning (LVPpostC) (10 x 30-s LV pacing during early reperfusion) groups were studied. Mechanical effects of LV pacing were determined using local pressure-length loops (sonomicrometry), whereas effects on myocardial lactate release and coronary flow were assessed from coronary effluent and fluorescent microspheres, respectively. Anesthetized pigs underwent 60-min coronary occlusion and 3-h reperfusion in control and right ventricular (RV) pacing postconditioning groups (RVPpostC) (10 x 30-s RV pacing during early reperfusion). In all hearts, area at risk and infarct size were determined with blue dye and triphenyltetrazolium chloride staining, respectively.
  
  
  RESULTS
  Infarct size, normalized to area at risk, was 47.0 +/- 12.3% in control rabbit hearts, but significantly smaller in LVPpreC (17.8 +/- 6.4%) and LVPpostC hearts (17.9 +/- 4.4%). Left ventricular pacing significantly altered regional mechanical work, but did not affect coronary flow or lactate release. In pigs, infarct size was significantly smaller in RVPpostC (9.8 +/- 3.0%) than in control (20.6 +/- 2.2%) animals.
  
  
  CONCLUSIONS
  Intermittent dyssynchrony during early reperfusion reduces infarct size in 2 different animal models. Dyssynchrony-induced postconditioning cannot be attributed to graded reperfusion but may be induced by modulation of local myocardial workload. Dyssynchrony-induced postconditioning opens new possibilities for cardioprotection in the clinical setting.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands. Ward.Vanagt@FYS.unimaas.nl
authors.forename: Ward Y
authors.initials: WY
authors.lastname: Vanagt
authors.forename: Richard N
authors.initials: RN
authors.lastname: Cornelussen
authors.forename: Tamara C
authors.initials: TC
authors.lastname: Baynham
authors.forename: Arne
authors.initials: A
authors.lastname: Van Hunnik
authors.forename: Quincy P
authors.initials: QP
authors.lastname: Poulina
authors.forename: Fawzi
authors.initials: F
authors.lastname: Babiker
authors.forename: Julio
authors.initials: J
authors.lastname: Spinelli
authors.forename: Tammo
authors.initials: T
authors.lastname: Delhaas
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D009924:Organ Culture Techniques; D011817:Rabbits; D013552:Swine; D016276:Ventricular Function / Q000502:physiology