Humphrey S M, Holliss D G, Cartner L A
J Surg Res. 1987 Aug;43(2):187-95. doi: 10.1016/0022-4804(87)90163-6.
The loss of the catabolic products of adenosine triphosphate in the form of purine nucleosides and oxypurines during ischemia and subsequent reperfusion may limit adenine nucleotide regeneration. This study compared the effects of infusion of inhibitors of the major reactions involved in the degradation of adenosine triphosphate to inosine on the postischemic recovery of high energy phosphate and myocardial function. Isolated rat hearts were made totally ischemic after a 5-min infusion of p1,p5-diadenosine pentaphosphate, alpha, beta-methylene adenosine diphosphate, nitrobenzyl-6-thioinosine, or erythro-9-(2-hydroxy-3-nonyl) adenine, which are inhibitors of adenylate kinase, 5'-nucleotidase, adenosine translocase, and adenosine deaminase, respectively. Following 30 min of ischemia, only hearts infused with alpha, beta-methylene adenosine diphosphate recovered significantly better ventricular function than did the control (P less than 0.05), but all hearts had increased adenosine triphosphate and creatine phosphate regeneration (P less than 0.05). The formation and washout of greater than 30% of the total adenine pool metabolites were not prevented by any drug. Nevertheless all manipulations of adenine metabolism resulted in recruitment of high energy phosphate during preischemic infusion which may have potential benefits in elective ischemic arrest.
在缺血及随后的再灌注过程中，三磷酸腺苷的分解产物以嘌呤核苷和氧嘌呤的形式流失，这可能会限制腺嘌呤核苷酸的再生。本研究比较了输注三磷酸腺苷降解为肌苷过程中主要反应的抑制剂，对缺血后高能磷酸的恢复及心肌功能的影响。在分别输注腺嘌呤核苷三磷酸、α,β-亚甲基二磷酸腺苷、硝基苄基-6-硫代肌苷或赤型-9-(2-羟基-3-壬基)腺嘌呤（分别为腺苷酸激酶、5'-核苷酸酶、腺苷转位酶和腺苷脱氨酶的抑制剂）5分钟后，将离体大鼠心脏制成完全缺血状态。缺血30分钟后，只有输注α,β-亚甲基二磷酸腺苷的心脏，其心室功能恢复明显优于对照组（P<0.05），但所有心脏的三磷酸腺苷和磷酸肌酸再生均增加（P<0.05）。任何药物均不能阻止超过30%的总腺嘌呤池代谢产物的形成和清除。然而，所有对腺嘌呤代谢的操作均导致在缺血前输注期间高能磷酸的补充，这可能对选择性缺血停搏具有潜在益处。
