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.