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Cardioprotective roles of adenosine against ischemic and reperfusion injury

腺苷对缺血和再灌注损伤的心脏保护作用

基本信息

批准号：
03670449
负责人：
HORI Masatsugu
金额：
$ 1.28万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

This study was undertaken to elucidate whether alpha_1-adrenoceptor activity is beneficial for contractile dysfunction during ischemia and reperfusion in open-chest dogs. Myocardial ischemia increased release of adenosine with reductions of coronary blood flow and fractional shortening. Prazosin (4 ug/kg/min, ic) further deteriorated contractile dysfunction with attenuated adenosine release and coronary blood flow. In turn, methoxamine (1ug/kg/min, ic), which does not affect basal coronary vascular tones, increased both adenosine release and coronary blood flow during ischemia and improved contractile function. This augmentation of adenosine release and coronary blood flow due to methoxamine increased fractional shortening, which was inhibited by 8-phenyltheophylline. These results indicate that alpha_1- adrenoceptor activity increases adenosine release during myocardial ischemia and attenuates contractile dysfunction.Furthermore, we examined the effects of alpha_1-adrenoceptor activity on myocardial stunning assessed at 3 hours after the onset of reperfusion followed by 15 min of complete occlusion of the left anterior descending coronary artery. Prazosin attenuated fractional shortening (12.7* 0.6 vs. 6.9 * 0.4 % with prazosin treatment, p<0.001). On the other hand, methoxamine attenuated contractile dysfunction. Both adenosine release and hyperemic coronary flow response during early reperfusion period were attenuated in the prazosin-treated group, and both were enhanced in the methoxamine-treated group. Thus we conclude that (1) alpha_1-adrenoceptor activity improves myocardial function during ischemia and reperfusion and (2) its cellular mechanism is due to enhanced adenosine release by alpha_1-adrenoceptor activity.

本研究旨在阐明α_1-肾上腺素能受体活性是否有利于开胸犬缺血再灌注时的收缩功能障碍。心肌缺血增加腺苷释放，冠状动脉血流量和缩短分数减少。哌唑嗪（4 μ g/kg/min，ic）进一步恶化收缩功能障碍，腺苷释放和冠状动脉血流量减少。相应地，甲氧胺（1微克/千克/分钟，ic），不影响基础冠状动脉血管张力，在缺血时增加腺苷释放和冠状动脉血流量，并改善收缩功能。甲氧胺增加腺苷释放和冠状动脉血流量，增加缩短分数，8-苯基茶碱抑制。这些结果表明，α_1-肾上腺素能受体活性增加腺苷释放在心肌缺血和减轻收缩功能障碍。此外，我们研究了α_1-肾上腺素能受体活性对心肌顿抑的影响，在3小时后开始再灌注，随后完全闭塞左前降支冠状动脉15分钟。哌唑嗪减弱缩短分数（12.7* 0.6 vs.哌唑嗪治疗的6.9 * 0.4%，p<0.001）。另一方面，甲氧胺减弱收缩功能障碍。在再灌注早期，哌唑嗪治疗组腺苷释放和充血的冠脉血流反应均减弱，而甲氧胺治疗组两者均增强。因此，我们认为：（1）α_1-肾上腺素能受体活性改善心肌缺血和再灌注时的功能;（2）其细胞机制是由于α_1-肾上腺素能受体活性增加腺苷释放。