Vanagt Ward Y, Cornelussen Richard N, Baynham Tamara C, Van Hunnik Arne, Poulina Quincy P, Babiker Fawzi, Spinelli Julio, Delhaas Tammo, Prinzen Frits W
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
J Am Coll Cardiol. 2007 May 1;49(17):1813-9. doi: 10.1016/j.jacc.2007.01.070. Epub 2007 Apr 16.
Considering the recent discovery of postconditioning, we investigated whether intermittent dyssynchrony immediately upon reperfusion induces cardioprotection as well.
Intermittent dyssynchrony, induced by ventricular pacing, preconditions myocardium.
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.
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.
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.
鉴于近期后适应的发现，我们研究了再灌注即刻出现的间歇性不同步是否也能诱导心脏保护作用。
心室起搏诱导的间歇性不同步可对心肌产生预处理作用。
对离体跳动的兔心脏进行30分钟冠状动脉闭塞和2小时再灌注。研究了对照组、左心室（LV）起搏预处理（LVPpreC）（3次5分钟LV起搏）和LV起搏后处理（LVPpostC）（再灌注早期10次30秒LV起搏）组。使用局部压力-长度环（声控测量法）测定LV起搏的机械效应，而分别从冠状动脉流出液和荧光微球评估对心肌乳酸释放和冠状动脉血流的影响。麻醉猪在对照组和右心室（RV）起搏后处理组（RVPpostC）（再灌注早期10次30秒RV起搏）中进行60分钟冠状动脉闭塞和3小时再灌注。在所有心脏中，分别用蓝色染料和氯化三苯基四氮唑染色测定危险区域面积和梗死面积。
以危险区域面积标准化后的梗死面积，在对照兔心脏中为47.0±12.3%，但在LVPpreC组（17.8±6.4%）和LVPpostC组心脏（17.9±4.4%）中显著更小。左心室起搏显著改变局部机械功，但不影响冠状动脉血流或乳酸释放。在猪中，RVPpostC组（9.8±3.0%）的梗死面积显著小于对照组（20.6±2.2%）动物。
再灌注早期的间歇性不同步可减小2种不同动物模型中的梗死面积。不同步诱导的后处理不能归因于分级再灌注，而可能是由局部心肌工作负荷的调节所诱导。不同步诱导的后处理为临床环境中的心脏保护开辟了新的可能性。
