Dissociation between early recovery of regional function and purine nucleotide content in postischaemic myocardium in the conscious dog.
Dissociation between early recovery of regional function and purine nucleotide content in postischaemic myocardium in the conscious dog.
复制标题
清醒狗缺血后心肌区域功能的早期恢复与嘌呤核苷酸含量之间的分离。
DOI：
10.1093/cvr/21.5.328
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发表时间：
1987
影响因子：
10.8
通讯作者：
Swain,JL
中科院分区：
文献类型：
--
作者：
Glower,DD;Spratt,JA;Newton,JR;Wolfe,JA;Rankin,JS;Swain,JL
由于局部心肌功能和核苷酸代谢的异常在短暂的冠状动脉闭塞后持续很长一段时间，因此在清醒的轻度镇静动物中研究了缺血后心肌中心肌功能障碍的消退和核苷酸池的补充之间的时间关系。在第二个实验中，输注5-氨基-4-咪唑甲酰胺核苷（AICA核苷），试图通过改变腺嘌呤核苷酸合成速率来影响心肌功能。清醒的狗轻度镇静吗啡进行冠状动脉闭塞15分钟，然后再灌注30分钟或12小时，在这个时候获得的心肌样品进行核苷酸分析。再灌注15 min时节段缩短平均为对照值的62%，再灌注12 h时增加至对照值的81%（p<0.05）。再灌注30分钟后，腺嘌呤核苷酸含量为对照组的75（5）%，在接下来的12小时再灌注中没有显著变化。因此，收缩功能的早期恢复并不伴随着总腺嘌呤核苷酸含量的可检测到的增加。在第二个实验中，近端嘌呤核苷酸合成途径的显著刺激发生，如通过肌苷一磷酸含量增加13倍至25倍所证明的。鸟嘌呤核苷酸库完全补充证明，远端嘌呤途径的一个分支也受到刺激，但另一个分支的产物（腺嘌呤核苷酸）没有显著增加。这些结果表明，在缺血后心肌的远端腺嘌呤核苷酸合成途径的选择性限制。研究结果表明，为了实现腺嘌呤核苷酸库的快速补充，刺激一磷酸肌苷远端嘌呤合成途径的药物可能是最成功的。
Since abnormalities in regional myocardial function and nucleotide metabolism persist for a prolonged period after a brief coronary occlusion the temporal relation between the resolution of myocardial dysfunction and repletion of nucleotide pools in postischaemic myocardium was studied in conscious mildly sedated animals. In a second experiment 5-amino-4-imidazolecarboxamide riboside (AICAriboside) was infused in an attempt to influence myocardial function by altering the rate of adenine nucleotide synthesis. Conscious dogs mildly sedated with morphine underwent coronary occlusion for 15 min followed by reperfusion for 30 min or 12 h, at which time a myocardial sample was obtained for nucleotide analysis. Segment shortening averaged 62% of control values at 15 min of reperfusion and increased to 81% of control by 12 h of reperfusion (p<0.05). Adenine nucleotide content was 75(5)% of control after 30 min of reperfusion and did not change significantly over the next 12 h of reperfusion. Thus the early return of systolic function was not accompanied by a detectable increase in total adenine nucleotide content. In the second experiment a pronounced stimulation of the proximal purine nucleotide synthetic pathway occurred as evidenced by a 13-fold to 25-fold increase in inosine monophosphate content. One branch of the distal purine pathway was also stimulated as evidenced by complete repletion of guanine nucleotide pools, but the product of the other branch (adenine nucleotides) did not increase significantly. These results indicate a selective limitation of the distal adenine nucleotide synthetic pathway in postischaemic myocardium. The findings suggest that to achieve rapid repletion of adenine nucleotide pools agents that stimulate the purine synthetic pathway distal to inosine monophosphate may be most successful.