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心肌缺血期间嘌呤代谢产物的积累:腺苷预处理与短暂缺血的比较。

Purine metabolite accumulation during myocardial ischemia: adenosine pretreatment versus brief ischemia.

作者信息

Manthei S A, Van Wylen D G

机构信息

Department of Biology, St. Olaf College, Northfield, MN 55057, USA.

出版信息

Basic Res Cardiol. 1997 Dec;92(6):368-77. doi: 10.1007/BF00796210.

DOI:10.1007/BF00796210
PMID:9464860
Abstract

Hearts preconditioned by brief ischemia are characterized by a reduced rate of cellular purine metabolite production during subsequent prolonged ischemia; the purpose of this study was to determine if transient exogenous adenosine pretreatment can mimic this phenomenon. The accumulation of interstitial fluid (ISF) purine metabolites during prolonged ischemia in untreated anesthetized dogs (n = 7) was compared to that in a group pretreated with brief ischemia (ischemic preconditioned group; n = 9), a group pretreated with 1.5 micromoles/min intracoronary adenosine (n = 7), and a group pretreated with 100 micromoles/min intracoronary adenosine (n = 7). Ischemic preconditioning was achieved by a 5 min period of left anterior descending coronary artery (LAD) occlusion followed by 10 min of reperfusion. The adenosine-treated groups were subjected to 10 min of intracoronary adenosine followed by 10 min of recovery. All animals were exposed to 60 min LAD occlusion followed by 60 min reperfusion. The changes in ISF adenosine and adenosine metabolites were assessed by cardiac microdialysis, using dialysate concentrations as indices of ISF levels. Ischemic preconditioning decreased the rate of dialysate adenosine and total purine accumulation during the prolonged ischemia. Although the two doses of exogenous adenosine bracketed the increase in ISF adenosine seen with ischemic preconditioning, neither adenosine dose was able to attenuate the rate of purine metabolite accumulation during prolonged ischemia. We conclude that exogenous adenosine pretreatment is unable to mimic the reduced ischemia-induced purine efflux that is characteristic of myocytes pretreated with brief ischemia.

摘要

经历短暂缺血预处理的心脏,其特征是在随后的长时间缺血期间细胞嘌呤代谢产物的生成速率降低;本研究的目的是确定短暂的外源性腺苷预处理是否能模拟这一现象。将未处理的麻醉犬(n = 7)在长时间缺血期间间质液(ISF)嘌呤代谢产物的积累情况,与短暂缺血预处理组(缺血预处理组;n = 9)、冠状动脉内以1.5微摩尔/分钟的速度注射腺苷的预处理组(n = 7)以及冠状动脉内以100微摩尔/分钟的速度注射腺苷的预处理组(n = 7)进行比较。通过左冠状动脉前降支(LAD)闭塞5分钟,随后再灌注10分钟来实现缺血预处理。腺苷处理组先接受10分钟的冠状动脉内腺苷注射,随后恢复10分钟。所有动物均经历60分钟的LAD闭塞,随后再灌注60分钟。采用心脏微透析法,以透析液浓度作为ISF水平指标,评估ISF中腺苷和腺苷代谢产物的变化。缺血预处理降低了长时间缺血期间透析液中腺苷和总嘌呤的积累速率。尽管两剂外源性腺苷的用量介于缺血预处理时ISF腺苷增加量之间,但两剂腺苷均未能在长时间缺血期间减弱嘌呤代谢产物的积累速率。我们得出结论,外源性腺苷预处理无法模拟短暂缺血预处理的心肌细胞所特有的缺血诱导嘌呤外流减少的现象。

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