Liu H, Cala P M, Anderson S E
Department of Human Physiology, One Shields Avenue, University of California, Davis, CA 95616-8644, USA.
J Mol Cell Cardiol. 1998 Mar;30(3):685-97. doi: 10.1006/jmcc.1997.0636.
In adult hearts, ischemic preconditioning (PC) has been shown to decrease ischemia-induced changes in intracellular pH (pHi) and [Ca] ([Ca]i) and decrease associated injury. These results are consistent with the interpretation that PC decreases the stimulus for Na uptake via Na/H exchange, thereby decreasing intracellular Na (Nai) accumulation, and thus decreasing the change in force driving Na/Ca exchange, which otherwise contributes to ischemia-induced increases in [Ca]i. Given documented age-related differences in myocardial responses to ischemia, we tested the hypothesis that in newborn hearts, PC will diminish intracellular [H], Nai, and [Ca]i during ischemia/reperfusion. NMR was used to measure pHi, Nai, [Ca]i, ATP, and PCr in isolated newborn (4-7 days) rabbit hearts Langendorff-perfused with Krebs-Henseleit solution equilibrated with 95% O2/5% CO2 at 36+/-1 degrees C. Control hearts were perfused 30 min before initiating 40 min global ischemia followed by 40 min reperfusion. PC hearts were treated the same except four 5-min intervals of ischemia each followed by 10 min of perfusion which preceded global ischemia. At end ischemia, pHi was higher in PC than control hearts (6.31+/-0.03 v 5.83+/-0.05; P<0.05). Similarly, PC diminished Nai-accumulation during ischemia and reperfusion (P<0.05). Control Nai rose from 16.2+/-2.6 to 108.8+/-10.3 (mEq/kg dry weight) and recovered to 55.2+/-10.1 and the corresponding values for PC hearts were 25.6+/-6.2, 70.0+/-7.9 and 21.9+/-5.2. PC also improved [Ca]i recovery during reperfusion (P<0.05). Control [Ca]i rose from 418+/-43 to 1100+/-78 (nm/l) and recovered to 773+/-63, whereas in PC hearts the values were 382+/-40, 852+/-136 and 371+/-45, respectively. In addition, PC decreased coronary resistance during reperfusion (P<0.05) as reflected by lower perfusion pressures under constant flow conditions (65.9+/-1.5 v 56. 1+/-4.1 mmHg at end of reperfusion). Finally, PC improved recovery of left-ventricular developed pressure (LVDP-43.8+/-12.0 v 17.2+/-3. 0% of control; P<0.05) and diminished CK release (607+/-245 v 2432+/-639 IU/g dry weight; P<0.05) during reperfusion. The results are consistent with the hypothesis.
在成年心脏中，缺血预处理（PC）已被证明可减少缺血诱导的细胞内pH值（pHi）和[Ca]（[Ca]i）变化，并减少相关损伤。这些结果与以下解释一致：PC减少了通过Na/H交换摄取Na的刺激，从而减少细胞内Na（Nai）积累，进而减少驱动Na/Ca交换的力的变化，否则这种变化会导致缺血诱导的[Ca]i增加。鉴于已记录的心肌对缺血反应的年龄相关差异，我们测试了以下假设：在新生心脏中，PC将在缺血/再灌注期间减少细胞内[H]、Nai和[Ca]i。核磁共振用于测量在36±1℃下用95% O2/5% CO2平衡的Krebs-Henseleit溶液进行Langendorff灌注的新生（4 - 7天）兔离体心脏中的pHi、Nai、[Ca]i、ATP和磷酸肌酸（PCr）。对照心脏在开始40分钟全心缺血前灌注30分钟，随后再灌注40分钟。PC组心脏的处理方式相同，只是在全心缺血前有四个5分钟的缺血间隔，每个间隔后接着10分钟的灌注。在缺血末期，PC组心脏的pHi高于对照组（6.31±0.03对5.83±０.05；P<0.05）。同样，PC减少了缺血和再灌注期间的Nai积累（P<0.05）。对照组的Nai从16.2±2.6上升到108.8±10.3（mEq/kg干重），并恢复到55.2±10.1，而PC组心脏的相应值分别为25.6±6.2、70.0±7.9和21.9±5.2。PC还改善了再灌注期间的[Ca]i恢复（P<0.05）。对照组的[Ca]i从418±43上升到1100±78（nm/l），并恢复到773±63，而在PC组心脏中，相应值分别为382±40、852±136和371±45。此外，PC降低了再灌注期间的冠状动脉阻力（P<0.05），这在恒定流量条件下较低的灌注压力中得到体现（再灌注末期为65.9±1.5对56.1±4.1 mmHg）。最后，PC改善了左心室舒张末压的恢复（LVDP - 43.8±12.0对对照组的17.2±3.0%；P<0.05），并减少了再灌注期间的肌酸激酶释放（607±245对2432±639 IU/g干重；P<0.05）。结果与假设一致。
