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PRECLINICAL STUDY

Pacing-Induced Dyssynchrony During Early Reperfusion Reduces Infarct Size

Ward Y. Vanagt, MD^_*,,_*, Richard N. Cornelussen, PhD^_*, Tamara C. Baynham, PhD, Arne Van Hunnik^_*, Quincy P. Poulina, MSc^_*, Fawzi Babiker, PhD^_*, Julio Spinelli, PhD, Tammo Delhaas, MD, PhD^_*, and Frits W. Prinzen, PhD^_*

^_* Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands
Department of Pediatrics, Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands
Guidant Corporation, St. Paul, Minnesota.

Manuscript received October 23, 2006; revised manuscript received January 2, 2007, accepted January 9, 2007.

^_* Reprint requests and correspondence: Dr. Ward Y. Vanagt, Department of Physiology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, the Netherlands. (Email: Ward.Vanagt{at}FYS.unimaas.nl).

Objectives: 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.

Abbreviations and Acronyms   LAD = left anterior descending coronary artery   LV = left ventricular   PCI = percutaneous coronary intervention   PTCA = percutaneous transluminal coronary angioplasty   RA = right atrial   RV = right ventricular   TTC = triphenyltetrazolium chloride   VPpostC = ventricular pacing postconditioning   VPpreC = ventricular pacing preconditioning