Flaherty Devin C, Hoxha Besim, Sun Jie, Gurji Hunaid, Simecka Jerry W, Olivencia-Yurvati Albert H, Mallet Robert T
Department of Integrative Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, Texas 76107-2699, USA.
Mil Med. 2010 Dec;175(12):1020-6. doi: 10.7205/milmed-d-10-00097.
Tourniquets impose ischemia on distal musculature. Resuscitation with pyruvate, an energy substrate and antioxidant, may ameliorate muscle ischemia-reperfusion injury.
After goats were exsanguinated to lower mean arterial pressure to 48 mmHg, femoral vessels were occluded for 90 minutes to impose hindlimb ischemia. Lactate Ringer's (LR) or pyruvate Ringer's (PR) solution was infused from 30 minutes ischemia until 30 minutes reperfusion. Pro- and antiapoptotic proteins and injury markers were measured in gastrocnemius at 4 hours reperfusion.
Pro-oxidant NADPH oxidase activity and nitrotyrosine content, a footprint of nitrosative stress, doubled, and poly (ADP-ribose) polymerase cleavage, an early apoptotic event, increased 80% in LR-resuscitated vs. sham muscle, but PR prevented these increases. Antiapoptotic Bcl-X(L) content fell in LR-treated vs. sham and PR-treated muscle. Water content increased in LR- but not PR-resuscitated muscle.
LR resuscitation imposed oxido-nitrosative stress and initiated proapoptotic mechanisms, while PR blunted these harmful consequences of muscle ischemia-reperfusion.
止血带会导致远端肌肉组织缺血。用丙酮酸(一种能量底物和抗氧化剂)进行复苏,可能会减轻肌肉缺血再灌注损伤。
将山羊放血使平均动脉压降至48 mmHg后,阻断股血管90分钟以造成后肢缺血。从缺血30分钟开始至再灌注30分钟,输注乳酸林格氏液(LR)或丙酮酸林格氏液(PR)。在再灌注4小时时,测量腓肠肌中的促凋亡蛋白和抗凋亡蛋白以及损伤标志物。
与假手术组肌肉相比,促氧化剂NADPH氧化酶活性和硝基酪氨酸含量(氧化应激的标志)增加了一倍,早期凋亡事件聚(ADP - 核糖)聚合酶裂解增加了80%,但PR可防止这些增加。与假手术组和PR处理的肌肉相比,LR处理的肌肉中抗凋亡蛋白Bcl - X(L)含量下降。LR复苏的肌肉中含水量增加,而PR复苏的肌肉中含水量未增加。
LR复苏会造成氧化亚硝化应激并启动促凋亡机制,而PR可减轻肌肉缺血再灌注的这些有害后果。