Ikeda Y, Gohra H, Hamano K, Zempo N, Ueyama T, Ohkusa T, Matsuzaki M, Esato K
First Department of Surgery, Yamaguchi University School of Medicine, Japan.
Jpn Circ J. 2001 Apr;65(4):330-4. doi: 10.1253/jcj.65.330.
Calcium overload is considered to be a primary contributor to ischemia-reperfusion injury. Cardiac sarcoplasmic reticulum (SR), the main regulator of intracellular Ca2+ concentration under normal conditions, is a target for ischemic myocardial injury. The ryanodine receptor (RyR) is the SR Ca2+ release channel. Previous reports have shown that a reduction in RyR activity during global myocardial ischemia correlates with concomitant myocardial dysfunction. Crystalloid cardioplegia, a technique for myocardial protection during heart operations, reduces Ca2+ accumulation during global ischemia. Hence, the effects of cardioplegia on RyR in isolated rabbit hearts was investigated. The study also compared [3H] ryanodine binding before ischemia (control group), after 30 min of ischemia (either global ischemia (GI group) or cardioplegic arrest (CA group)), and after 20 min of reperfusion. The GI group, but not the CA group, showed a significant reduction in the maximum number of binding sites (Bmax) for RyR compared with the control group (Control vs GI group: after ischemia, 1.33+/-0.27 vs 0.83+/-0.12 pmol/mg protein, p<0.05; after reperfusion, 1.33+/-0.27 vs 0.80+/-0.08 pmol/mg protein; p<0.05). CA group: after ischemia, 1.22+/-0.20 pmol/mg protein; after reperfusion, 1.15+/-0.28 pmol/mg protein). The affinity (Kd) values for [3H] ryanodine binding were not different among the 3 groups at any point. The preservation of RyR numbers during cardioplegia correlated with the concomitant preservation of cardiac functions. The results indicate that number of functional RyR was much better preserved during cardioplegia than during global ischemia. It is postulated that cardioplegia-induced protection of cardiac RyR may result in the protection of SR function during ischemia-reperfusion.
钙超载被认为是缺血再灌注损伤的主要促成因素。心肌肌浆网（SR）是正常情况下细胞内Ca2+浓度的主要调节者，是缺血性心肌损伤的靶点。兰尼碱受体（RyR）是肌浆网Ca2+释放通道。先前的报道表明，在全心缺血期间RyR活性降低与心肌功能障碍相关。晶体停搏液是心脏手术期间心肌保护技术，可减少全心缺血期间的Ca2+蓄积。因此，研究了停搏液对离体兔心脏中RyR的影响。该研究还比较了缺血前（对照组）、缺血30分钟后（全心缺血（GI组）或停搏液灌注停搏（CA组））以及再灌注20分钟后的[3H]兰尼碱结合情况。与对照组相比，GI组而非CA组显示RyR结合位点的最大数量（Bmax）显著减少（对照组与GI组：缺血后，1.33±0.27对0.83±0.12 pmol/mg蛋白，p<0.05；再灌注后，1.33±0.27对0.80±0.08 pmol/mg蛋白；p<0.05）。CA组：缺血后，1.22±0.20 pmol/mg蛋白；再灌注后，1.15±0.28 pmol/mg蛋白）。在任何时间点，3组之间[3H]兰尼碱结合的亲和力（Kd）值均无差异。停搏液期间RyR数量的保留与心脏功能的保留相关。结果表明，与全心缺血期间相比，停搏液期间功能性RyR的数量得到了更好的保留。据推测，停搏液诱导的对心脏RyR的保护可能导致缺血再灌注期间肌浆网功能的保护。
