Dhasmana J P, Digerness S B, Geckle J M, Ng T C, Glickson J D, Blackstone E H
J Cardiovasc Pharmacol. 1983 Nov-Dec;5(6):1040-7. doi: 10.1097/00005344-198311000-00019.
The concept of limiting irreversible damage due to ischemic arrest by inhibiting nucleoside breakdown was tested in the isolated perfused rat heart. Functional recovery measurements were combined with continuous high-energy phosphate measurements by means of 31P nuclear magnetic resonance (NMR) and with nucleoside release measurements in the reperfusion period. The adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and 2'-deoxycoformycin (DCF) were given 5 min before ischemia and for the first 5 min of reperfusion. These treated groups were compared with a control, untreated group. These were further compared with a group of hearts arrested with potassium and to a group combining potassium arrest and EHNA. It was found that all treated groups recovered mechanical function significantly better than the untreated group. DCF, K+, and K+ + EHNA slowed ATP decline and resulted in better ATP recovery than untreated or EHNA-treated, and all treatments decreased nucleoside base release. Intracellular pH fell equally in all groups and recovered to preischemic values. Thus, these adenosine deaminase inhibitors improve functional recovery following ischemia, although this improvement was not well correlated with purine losses observed during reperfusion.
通过抑制核苷分解来限制缺血性停搏所致不可逆损伤的概念在离体灌注大鼠心脏中进行了测试。功能恢复测量与通过31P核磁共振（NMR）进行的连续高能磷酸盐测量以及再灌注期核苷释放测量相结合。在缺血前5分钟和再灌注的前5分钟给予腺苷脱氨酶抑制剂erythro-9-(2-羟基-3-壬基)腺嘌呤（EHNA）和2'-脱氧助间型霉素（DCF）。将这些治疗组与未治疗的对照组进行比较。进一步将它们与一组用钾停搏的心脏以及一组联合钾停搏和EHNA的心脏进行比较。发现所有治疗组的机械功能恢复均明显优于未治疗组。DCF、K+以及K+ + EHNA减缓了ATP下降，并导致比未治疗或EHNA治疗组更好的ATP恢复，且所有治疗均减少了核苷碱基释放。所有组的细胞内pH均同等下降，并恢复到缺血前值。因此，这些腺苷脱氨酶抑制剂可改善缺血后的功能恢复，尽管这种改善与再灌注期间观察到的嘌呤损失相关性不佳。
