Bolling S F, Childs K F, Ning X H
Thoracic Surgery Research Laboratory, University of Michigan Medical School, Ann Arbor 48109.
J Surg Res. 1992 Oct;53(4):342-8. doi: 10.1016/0022-4804(92)90059-9.
During induced myocardial ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is inhibited as anaerobic pathways predominate. Even following reperfusion, stunned myocardium uses oxygen and substrate inefficiently leading to poor functional recovery as less mechanical work is developed per oxygen utilized. Amino acids potentially can act as cardiac metabolic substrates during and after ischemia, utilizing the transamination of amino acids by the malate-aspartate shuttle to form high energy phosphates via the tricarboxylic acid cycle. We investigated if "preloading" hearts with a physiologic spectrum of amino acids could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were "preloaded" with a 0.05% amino acid perfusion for 30 min prior to cardioplegic ischemia. Following reperfusion, analysis of functional recovery revealed that contractility and cardiac efficiency were improved with amino acids substrate preloading. The mechanism of this may be due to uptake of amino acids prior to ischemia, which are later utilized for internal reparative work during ischemia and external contractile work after ischemia.
在心脏手术诱导的心肌缺血过程中,会发生心肌顿抑,葡萄糖、脂肪酸和乳酸的有氧代谢受到抑制,因为无氧代谢途径占主导地位。即使在再灌注后,顿抑心肌对氧气和底物的利用效率也很低,导致功能恢复不佳,因为每利用一分子氧气产生的机械功较少。氨基酸在缺血期间及之后可能作为心脏代谢底物,通过苹果酸 - 天冬氨酸穿梭进行氨基酸转氨作用,经由三羧酸循环形成高能磷酸化合物。我们研究了用生理范围内的氨基酸“预负荷”心脏是否能增强缺血后心肌的恢复。将离体灌注的兔心脏进行34℃心脏停搏缺血120分钟。心脏仅接受心脏停搏液作为对照,或在心脏停搏缺血前用0.05%的氨基酸灌注“预负荷”30分钟。再灌注后,功能恢复分析显示,氨基酸底物预负荷可改善收缩力和心脏效率。其机制可能是由于缺血前氨基酸的摄取,随后这些氨基酸在缺血期间用于内部修复工作,在缺血后用于外部收缩工作。