Bolling S F, Childs K F, Ning X H
Thoracic Surgery Research Laboratory, University of Michigan Medical School, Ann Arbor 48109, USA.
J Surg Res. 1995 Jul;59(1):174-8. doi: 10.1006/jsre.1995.1150.
During induced ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is altered. Following reperfusion, stunned myocardium uses oxygen and substrate inefficiently, leading to poor functional recovery. However, amino acids may be used as anaplerotic metabolic substrates during and after ischemia, utilizing transamination of amino acids to form high-energy phosphates via the tricarboxylic acid cycle. We investigated if loading hearts with a physiologic spectrum of amino acids prior to ischemia 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 loaded with a 0.05, 0.1, 0.5, 1, 2, or 5% amino acid perfusion prior to cardioplegic ischemia. Following reperfusion, functional recovery revealed that hearts perfused with 0.05 and 0.1% amino acids had improved contractility and compliance vs untreated controls. To determine if the mechanism of amino acid loading in improving postischemic function was enhancement of high-energy phosphate resynthesis, nucleotides and nucleosides were measured. While all preischemic values were equivalent, amino-acid-loaded hearts had significantly greater high energy nucleotides at end ischemia and after reperfusion. These data demonstrate that metabolism, as well as function, is improved with amino acid loading prior to ischemia, which allowed for better internal reparative work during ischemia and external contractile work after ischemia. This strategy may have application in cardiac surgery.
在心脏手术诱导缺血期间,会发生心肌顿抑,葡萄糖、脂肪酸和乳酸的有氧代谢会发生改变。再灌注后,顿抑心肌对氧气和底物的利用效率低下,导致功能恢复不佳。然而,氨基酸可在缺血期间及之后用作补充性代谢底物,通过氨基酸的转氨作用经三羧酸循环形成高能磷酸酯。我们研究了在缺血前给心脏加载生理范围内的氨基酸是否能增加缺血后心肌的恢复。将离体灌注兔心置于34℃停搏缺血120分钟。心脏单独接受停搏液作为对照,或在停搏缺血前加载0.05%、0.1%、0.5%、1%、2%或5%的氨基酸灌注。再灌注后,功能恢复显示,与未处理的对照相比,灌注0.05%和0.1%氨基酸的心脏收缩性和顺应性有所改善。为了确定氨基酸加载改善缺血后功能的机制是否是高能磷酸酯再合成的增强,对核苷酸和核苷进行了测量。虽然所有缺血前的值都相当,但加载氨基酸的心脏在缺血末期和再灌注后具有明显更多的高能核苷酸。这些数据表明,缺血前加载氨基酸可改善代谢及功能,这使得在缺血期间有更好的内部修复工作,在缺血后有更好的外部收缩工作。这种策略可能在心脏手术中具有应用价值。