Muscari C, Finelli C, Stefanelli C, Flamigni F, Guarnieri C, Caldarera C M
Department of Biochemistry, University of Bologna, Italy.
Mech Ageing Dev. 1993 Feb;67(1-2):1-11. doi: 10.1016/0047-6374(93)90107-3.
The hearts of young (6 months) and aged (24 months) rats, paced at a frequency of 300 bpm, were perfused by the Langendorff technique and subjected to: 20 min of equilibration perfusion, 30 min of global ischemia (95% reduction of the coronary flow) and 20 min of reperfusion. The control group was equilibrated for 20 min and then aerobically perfused for 50 min. After 20 min of stabilization, ATP and ADP levels and the adenine nucleotide pool were significantly higher in young than aged hearts (15% increase), but no modifications were found between the two age groups after 50 min of aerobic perfusion. Even the energy charge did not change under aerobic conditions. At the end of the ischemic period the levels of ATP and ADP decreased to a similar extent in young and aged hearts. After 20 min of reperfusion the myocardial level of ATP remained lower in comparison to the preischemic and control values in both age groups. At the end of the reperfusion there was a decrease in energy charge and creatine phosphate levels in the aged group in respect to the young group. The concentrations of adenosine, hypoxanthine and xanthine in coronary effluents did not change during ischemia and reperfusion irrespective of the age of the animals. On the contrary, the release of uric acid during ischemia and reperfusion was greater in aged than young hearts (90% increase). Moreover, the level of inosine in perfusates during the ischemic period was significantly lower in the 24-month-old group (30% decrease). These results are in accordance with the increased purine nucleoside phosphorylase activity and the decreased hypoxanthine phosphorybosyl-transferase activity found in the myocardium of the aged vs. young rats at the end of the reperfusion period. These data indicate that in the aged rat hearts, when exposed to ischemic and reperfusion conditions, there is a modification of purine breakdown which leads to a greater production of uric acid in respect to that found in young hearts.
采用Langendorff技术对年轻（6个月）和老年（24个月）大鼠的心脏进行灌注，起搏频率为300次/分钟，并进行以下处理：20分钟的平衡灌注、30分钟的全心缺血（冠状动脉血流减少95%）和20分钟的再灌注。对照组平衡20分钟，然后进行50分钟的有氧灌注。稳定20分钟后，年轻心脏中的ATP、ADP水平和腺嘌呤核苷酸池显著高于老年心脏（增加15%），但在有氧灌注50分钟后，两个年龄组之间未发现变化。即使在有氧条件下，能荷也没有改变。在缺血期结束时，年轻和老年心脏中的ATP和ADP水平下降程度相似。再灌注20分钟后，两个年龄组的心肌ATP水平均低于缺血前和对照组的值。再灌注结束时，老年组的能荷和磷酸肌酸水平相对于年轻组有所下降。无论动物年龄如何，冠状动脉流出液中腺苷、次黄嘌呤和黄嘌呤的浓度在缺血和再灌注期间均未改变。相反，老年心脏在缺血和再灌注期间尿酸的释放量比年轻心脏更大（增加90%）。此外，在缺血期，24个月龄组灌注液中的肌苷水平显著降低（降低30%）。这些结果与再灌注期结束时老年大鼠心肌中嘌呤核苷磷酸化酶活性增加和次黄嘌呤磷酸核糖转移酶活性降低一致。这些数据表明，在老年大鼠心脏中，当暴露于缺血和再灌注条件时，嘌呤分解发生改变，导致相对于年轻心脏产生更多的尿酸。
