ENHANCED FUNCTIONAL PRESERVATION OF COLD‐STORED RAT HEART BY A NUCLEOSIDE TRANSPORT INHIBITOR1
ENHANCED FUNCTIONAL PRESERVATION OF COLD‐STORED RAT HEART BY A NUCLEOSIDE TRANSPORT INHIBITOR1
复制标题
通过核苷转运抑制剂增强冷藏大鼠心脏的功能保存1
DOI：
10.1097/00007890-199407000-00006
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发表时间：
1994
期刊：
影响因子：
6.2
通讯作者：
T. Wang
中科院分区：
文献类型：
--
作者：
X. Yang;Q. Zhu;M. Claydon;G. Hicks;T. Wang
本研究探讨了低温保存过程中抑制核苷转运可提高组织腺苷(ADO)含量并改善大鼠离体心功能的假说。用含有不同浓度(0-100 nm)核苷转运抑制剂S-(4-硝基苄基)-6-硫代肌苷(NBTI)的停搏液冲洗心脏，在0$DGC中浸泡保存9小时。在工作再灌流30min后进行功能评估。未保存的新鲜心脏的功能作为对照，保存后的恢复以控制功能的百分比报告。各组保存后心率在再灌流后均恢复到对照水平。无NBTI组其他功能指标恢复正常：主动脉血流量(AF)56.2pm4.6%，冠脉流量(CF)53.9pm3.2%，心输出量(CO)55.5pm4.0%，收缩压81.6pm2.5%，功47.0pm4.2%，冠脉阻力(CVR)157.1pm7.8%。NBTI以剂量依赖的方式促进功能恢复；5 nM剂量时恢复最大，AF为781pm3.4%，CF为73.5pm4.4%，CO为76.7pm3.6%，Work为70.7pm5.0%，CVR为对照组的127.5pm4.5%(P<；0.05比无NBTI)。ADOA1受体拮抗剂1，3-二丙基-8-环戊基黄嘌呤(0.1nMUM)可阻断5 nM NBTI的作用，AF、CF、CO、Work和CVR的恢复分别为对照组的62.8 pm8.0%、58.3 pm5.0%、61.5 pm3.9%、54.4 pm4.5%和163.8 pm12.7%(P<；0.05 vs.5 nMμ)。保存结束时，5 nM NBTI心脏组织中ADO含量为0.075pm0.025μumol/g干重量，显著高于非NBTI心脏的0.016 pm0.004μumol/g干重量。5 nM NBTI心脏在再灌流初期嘌呤释放延迟，表明NBTI抑制核苷转运。但NBTI治疗并不能改善心肌的末端储存或再灌注期的ATP。总之，在停搏液中加入NBTI可提高组织ADO，改善低温保存大鼠心脏的保存后功能。这种作用是由ADO A1受体介导的，而不调用能量守恒。
This study investigates the hypothesis that inhibition of nucleoside transport during hypothermic storage elevates tissue adenosine (ADO) content and improves the function of the isolated rat heart. The hearts, flushed with a cardioplegic solution containing varying concentrations (0–100 nM) of a nucleoside transport inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI), were immersion-stored at 0$dGC for 9 hr. Function was assessed after 30 min of working reperfusion. Function of unstored fresh hearts served as controls and poststorage recovery is reported as percentage of control function. Poststorage heart rate in all groups returned to control level after reperfusion. Recovery of other functional parameters in the no-NBTI group was as follows: aortic flow (AF), 56.2pm4.6%; coronary flow (CF), 53.9pm3.2%; cardiac output (CO), 55.5pm4.0%; systolic pressure, 81.6pm2.5%; work, 47.0pm4.2%; and coronary vascular resistance (CVR), 157.1pm7.8% of control. NBTI improved functional recovery in a dose-dependent fashion; the maximal improvement was seen at a dose of 5 nM, in which the recovery was; AF, 78.1pm3.4%; CF, 73.5pm4.4%; CO, 76.7pm3.6%; work, 70.7pm5.0%; and CVR, 127.5pm4.5% of control (P<0.05 vs. no-NBTI). The ADO A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (0.1 μUM) blocked the effects of 5 nM NBTI; the recovery of AF, CF, CO, work, and CVR decreased to 62.8pm8.0%, 58.3pm5.0%, 61.5pm3.9%, 54.4pm4.5%, and 163.8pm12.7% of control, respectively (P<0.05 vs. 5 nM NBTI). Tissue ADO content in 5 nM NBTI hearts at the end of storage was 0.075pm0.025 μUmol/g dry wt, which was significantly elevated from 0.016pm0.004 μUmol/g dry wt in no-NBTI hearts. Purine release during initial reperfusion was delayed in 5 nM NBTI hearts, indicating the inhibition of nucleoside transport by NBTI. But NBTI treatment did not improve end-storage or end-reperfusion myocardial ATP. In conclusion, the addition of NBTI to cardioplegic solution enhanced tissue ADO and improved poststorage function of the hypothermically stored rat heart. The effect is ADO A1-receptor mediated without invoking energy conservation.