Kim-Lee M H, Stokes B T, McDonald J S
Department of Physiology, Ohio State University, Columbus 43210.
Anesth Analg. 1994 Oct;79(4):728-33. doi: 10.1213/00000539-199410000-00019.
The purpose of this study was to determine the effects of local anesthetics (lidocaine and procaine) and hypothermic perfusion on Na+/Ca2+ exchanger activity during reperfusion-induced calcium paradox in vitro. Hypothetically, this work provides a mechanism for reperfusion paradox injury in vitro that may relate to a variety of ischemic insults in vivo. Intracellular calcium ([Ca2+]i) in individual cells was measured using a fura-2 photometry system during protocols previously shown to dramatically and persistently increase [Ca2+]i in a manner that replicates certain phases of reperfusion injury in vivo. Our results suggest that short (< 5.0 min) exposure to hypocalcia prompts subsequent, potentially lethal, sodium-dependent calcium entry via the reverse phase of the Na+/Ca2+ exchanger. The local anesthetics lidocaine or procaine are able to block [Ca2+]i increases when added at the time of reperfusion. Furthermore, since [Ca2+]i is normally increased when local anesthetics are added by themselves, the results suggest that local anesthetics promote the forward mode of Na+/Ca2+ exchange (i.e., Na-dependent calcium removal) in addition to reverse Na+/Ca2+ exchanger blockade. Low temperature (18 degrees C) perfusion or reperfusion also affects exchanger dynamics and attenuates calcium entry during such protocols. These experiments further implicate the Na+/Ca2+ exchanger in reperfusion-mediated cell injury and provide potential ways to therapeutically modify such phenomena in vivo.
本研究的目的是确定局部麻醉药（利多卡因和普鲁卡因）及低温灌注对体外再灌注诱导的钙反常过程中Na⁺/Ca²⁺交换体活性的影响。从理论上讲，这项工作为体外再灌注反常损伤提供了一种机制，这可能与体内的各种缺血性损伤有关。在先前已证明能以复制体内再灌注损伤某些阶段的方式显著且持续增加细胞内钙浓度（[Ca²⁺]i）的实验方案中，使用fura-2荧光光度系统测量单个细胞内的[Ca²⁺]i。我们的结果表明，短时间（<5.0分钟）暴露于低钙环境会促使随后通过Na⁺/Ca²⁺交换体的反向转运导致潜在致命的钠依赖性钙内流。在再灌注时加入局部麻醉药利多卡因或普鲁卡因能够阻止[Ca²⁺]i升高。此外，由于单独加入局部麻醉药时[Ca²⁺]i通常会升高，结果表明局部麻醉药除了阻断Na⁺/Ca²⁺交换体外，还能促进其正向转运模式（即钠依赖性钙外流）。低温（18℃）灌注或再灌注也会影响交换体动力学，并在这些实验方案中减弱钙内流。这些实验进一步表明Na⁺/Ca²⁺交换体与再灌注介导的细胞损伤有关，并提供了在体内对这种现象进行治疗性干预的潜在方法。
