Siegmund B, Balser C, Ladilov Y V, Piper H M
Physiologisches Institut Justus-Liebig-Universität, Giessen, Germany.
Basic Res Cardiol. 1998;93 Suppl 3:17-20. doi: 10.1007/s003950050198.
Previous studies have shown that SIN-1C (N-morpholinoiminoacetonitrile) can protect ischemic-reperfused myocardium. The aim of the present study was to analyse on the cellular level the mechanism by which SIN-1C may exert this effect. To simulate ischemia-reperfusion, isolated adult rat cardiomyocytes were incubated at pH 6.4 under anoxia and reoxygenated at pH 7.4 in presence or absence of SIN-1C. Reoxygenation was started when intracellular Ca2+ (measured with fura-2) had increased to > or = 10(-5) mol/L and pHi (BCECF) decreased to 6.6. Development of hypercontracture was determined microscopically. In the control group reoxygenation provoked oscillations of cytosolic Ca2+ (60.9 +/- 9.6 min-1 at 5 min of reoxygenation) accompanied by development of hypercontracture (to 77.2 +/- 3.8% of end-ischemic cell length). When SIN-1C was added upon reoxygenation, Ca2+ oscillations were markedly reduced (27.0 +/- 4.5 min-1, p < 0.001) and hypercontracture virtually abolished (90.6 +/- 2.0% of end-ischemic cell length, p < 0.001). SIN-1C did not influence the recovery of pHi during reoxygenation. The results indicate that SIN-1C protects cardiomyocytes against reoxygenation-induced hypercontracture by its ability to suppress oscillations of intracellular Ca2+ during the early phase of reoxygenation.
先前的研究表明，SIN-1C（N-吗啉代亚氨基乙腈）可保护缺血再灌注心肌。本研究的目的是在细胞水平上分析SIN-1C发挥这种作用的机制。为模拟缺血再灌注，将分离的成年大鼠心肌细胞在缺氧条件下于pH 6.4孵育，然后在有或无SIN-1C存在的情况下于pH 7.4复氧。当细胞内Ca2+（用fura-2测量）增加至≥10(-5) mol/L且细胞内pH值（BCECF）降至6.6时开始复氧。通过显微镜观察确定超收缩的发展情况。在对照组中，复氧引发了胞质Ca2+振荡（复氧5分钟时为60.9±9.6次/分钟），同时伴有超收缩的发展（达到缺血末期细胞长度的77.2±3.8%）。当在复氧时加入SIN-1C，Ca2+振荡明显减少（27.0±4.5次/分钟，p<0.001），超收缩几乎完全消除（缺血末期细胞长度的90.6±2.0%，p<0.001）。SIN-1C不影响复氧期间细胞内pH值的恢复。结果表明，SIN-1C通过在复氧早期抑制细胞内Ca2+振荡的能力来保护心肌细胞免受复氧诱导的超收缩。
