van Vuuren Derick, Genis Amanda, Genade Sonia, Lochner Amanda
Department of Biomedical Sciences, Division of Medical Physiology, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, Tygerberg, 7505, Republic of South Africa.
Cardiovasc Drugs Ther. 2008 Oct;22(5):391-7. doi: 10.1007/s10557-008-6119-6. Epub 2008 Jun 19.
Despite the attention focussed on postconditioning (postC; brief cycles of reperfusion/ischaemia at the onset of reperfusion, conferring cardioprotection against reperfusion injury), an infarct sparing effect for postC in the isolated working heart model has not been reported. The purpose of this study was to develop a cardioprotective postC protocol in this model.
Hearts from male Wistar rats (210-350 g) were perfused either retrogradely (Langendorff) or in the working mode. For functional studies 30 or 35 min global ischaemia (GI) and 20 or 25 min GI were applied in the Langendorff and working heart models respectively. Infarct size was measured after 35 min regional ischaemia (RI) in both models. In the latter studies hearts were subdivided into low (36.5 degrees C) and high (37 degrees C) temperature groups (during both ischaemia and initial reperfusion). In all groups hearts were either freely reperfused (nonPostC) or postconditioned (postC) by 6x10 s ischaemia/reperfusion cycles.
In both perfusion modes postC only elicited an infarct sparing effect after a slight elevation in temperature to 37 degrees C (Langendorff: L-nonPostC=47.99+/-3.31% vs. L-postC=27.81+/-2.49%, p<0.0001; and work=W-nonPostC: 35.81+/-3.67% vs. W-postC=17.74+/-2.72%, p<0.001). However, only in the Langendorff group could postC conserve post-ischaemic function, while no significant recoveries were seen in the working hearts.
We demonstrated an infarct sparing effect for postC in the working heart model, which unlike the Langendorff model, was not associated with functional preservation. The infarct sparing effect of postC in both models was however extremely sensitive to even slight fluctuations in temperature.
尽管人们对缺血后适应(postC;再灌注开始时短暂的再灌注/缺血周期,可对再灌注损伤起到心脏保护作用)给予了关注,但在离体工作心脏模型中尚未报道postC具有梗死面积缩小效应。本研究的目的是在该模型中制定一种具有心脏保护作用的postC方案。
用雄性Wistar大鼠(210 - 350 g)的心脏进行逆行灌注(Langendorff法)或工作模式灌注。在功能研究中,Langendorff模型和工作心脏模型分别采用30或35分钟的全心缺血(GI)以及20或25分钟的GI。在两种模型中,均在35分钟局部缺血(RI)后测量梗死面积。在后续研究中,心脏被分为低温(36.5℃)和高温(37℃)组(缺血和初始再灌注期间)。所有组的心脏要么自由再灌注(非postC),要么通过6次10秒的缺血/再灌注周期进行后适应(postC)。
在两种灌注模式下,仅在温度轻微升高至37℃后,postC才产生梗死面积缩小效应(Langendorff法:L - 非postC = 47.99±3.31%,vs. L - postC = 27.81±2.49%,p < 0.0001;工作模式:W - 非postC = 35.81±3.67%,vs. W - postC = 17.74±2.72%,p < 0.001)。然而,只有在Langendorff组中,postC能保留缺血后功能,而在工作心脏中未观察到明显恢复。
我们在工作心脏模型中证明了postC具有梗死面积缩小效应,与Langendorff模型不同的是,它与功能保留无关。然而,两种模型中postC的梗死面积缩小效应对温度的微小波动都极为敏感。