Goldberg Steven P, Digerness Stanley B, Skinner Jonathan L, Killingsworth Cheryl R, Katholi Charles R, Holman William L
Department of Surgery, School of Medicine, University of Alabama at Birmingham, 35294-0007, USA.
Ann Thorac Surg. 2002 Feb;73(2):569-74. doi: 10.1016/s0003-4975(01)03309-4.
Intramyocyte sodium (Na+) increases during ischemia and reperfusion, which causes myocardial calcium (Ca2+) uptake and leads to myocyte injury or death. This study determines if ischemic preconditioning and myocyte sodium-hydrogen ion (Na+-H+) exchange (NHE) inhibition decreases Na+ gain that otherwise occurs with cardioplegic arrest and reperfusion.
Pigs had 1 hour of cardioplegic arrest followed by reperfusion. Group 1 had no intervention (controls). Group 2 received dimethyl amiloride (DMA, an NHE inhibitor), and group 3 had ischemic preconditioning before cardioplegic arrest. Precardioplegia to postreperfusion change in intramyocyte ion content was measured with atomic absorption spectrometry. The time to initial electrical activity and number of defibrillations needed to establish an organized rhythm postreperfusion were used as electrophysiologic variables to measure ischemia-reperfusion injury.
Intramyocyte Na+ content for group 1 increased from 45.9+/-6.7 to 61.9+/-22.5 micromol/g (p = 0.02). Group 2 had an insignificant decrease in intramyocyte Na+ of 27.7+/-19.58 micromol/g (p = 0.06), and group 3 had an insignificant decrease of 10.8+/-46.33 micromol/g (p = 0.48). Interstitial water increased significantly in all groups, but there were no significant increases in intramyocyte water content. Electrophysiologic recovery was similar for all three groups.
The NHE inhibition and ischemic preconditioning each eliminated the increase in intramyocyte Na+ content that otherwise occurred with cardioplegic arrest and reperfusion in this porcine model. Because their mechanisms are distinct, it is possible that an additive beneficial effect against ischemia-reperfusion injury can be achieved by using NHE inhibition together with a preconditioning stimulus as prereperfusion therapy.
在缺血和再灌注期间，心肌细胞内的钠（Na+）会增加，这会导致心肌钙（Ca2+）摄取增加，并导致心肌细胞损伤或死亡。本研究旨在确定缺血预处理和心肌细胞钠-氢离子（Na+-H+）交换（NHE）抑制是否能减少在心脏停搏和再灌注时否则会发生的Na+增加。
猪经历1小时心脏停搏，随后进行再灌注。第1组不进行干预（对照组）。第2组接受二甲基氨氯吡脒（DMA，一种NHE抑制剂），第3组在心脏停搏前进行缺血预处理。用原子吸收光谱法测量心脏停搏前至再灌注后心肌细胞内离子含量的变化。将初始电活动时间和再灌注后建立有组织节律所需的除颤次数用作测量缺血-再灌注损伤的电生理变量。
第1组心肌细胞内Na+含量从45.9±6.7微摩尔/克增加到61.9±22.5微摩尔/克（p = 0.02）。第2组心肌细胞内Na+有不显著的减少，为27.7±19.58微摩尔/克（p = 0.06），第3组有不显著的减少，为10.8±46.33微摩尔/克（p = 0.48）。所有组间质水均显著增加，但心肌细胞内水含量无显著增加。三组的电生理恢复情况相似。
在该猪模型中，NHE抑制和缺血预处理均消除了心脏停搏和再灌注时否则会发生的心肌细胞内Na+含量增加。由于它们的机制不同，将NHE抑制与预处理刺激联合用作再灌注前治疗有可能对缺血-再灌注损伤产生相加的有益作用。
