INCREASED ADENOSINE CONCENTRATION IN BLOOD FROM ISCHEMIC MYOCARDIUM BY AICA RIBOSIDE - EFFECTS ON FLOW, GRANULOCYTES, AND INJURY
INCREASED ADENOSINE CONCENTRATION IN BLOOD FROM ISCHEMIC MYOCARDIUM BY AICA RIBOSIDE - EFFECTS ON FLOW, GRANULOCYTES, AND INJURY
复制标题
DOI：
10.1161/01.cir.80.5.1400
复制
发表时间：
1989-11-01
期刊：
影响因子：
37.8
通讯作者：
ENGLER, RL
中科院分区：
文献类型：
--
作者：
GRUBER, HE;HOFFER, ME;ENGLER, RL
如果局部心肌腺苷浓度增加，则急性冠状动脉闭塞的发病率和死亡率可以降低，因为1）缺血期间冠状动脉侧支血流量随着腺苷输注而增加，和2）缺血期间微循环中积聚的粒细胞在很大程度上被腺苷抑制产生超氧阴离子自由基，抑制粘附到血管内皮，以及损伤培养中的内皮细胞。利用培养的淋巴母细胞模型系统，我们发现5-氨基-4-咪唑甲酰胺（AICA）核苷增强ATP催化过程中腺苷的积累。因此，在犬心肌中使用AICA核苷预处理以在1小时缺血期间选择性地增加缺血区域中的腺苷浓度。在缺血5分钟时，盐水处理的和AICA核苷处理的狗中缺血心肌的内皮素流量为0.06 ± 0.05。0.03和0.34 ±。0.11 ml/min/g（P < 0.01），对非缺血心肌的血流无影响。在AICA核苷治疗的狗中，室性心动过速和室性早搏去极化显著减弱。AICA核苷对血压和心率没有影响。在来自缺血组织的静脉血中，腺苷从检测不到的水平（< 0.01 μ M）增加到0.22 ± 0.01 μ M。0.08生理盐水中的1.79 μ M和1.79 μ M ± 0.05 μ M。0.06在AICA核苷处理的狗中分别为μ M（p < 0.001）。冠状静脉肌苷浓度在生理盐水中比在AICA核苷治疗的狗。在单独的体外研究中，AICA核苷没有改变犬血液中腺苷的去除率，与盐水治疗的犬相比，AICA核苷治疗的犬缺血心肌中铟标记的粒细胞积聚显著减少。此外，腺苷，但不是AICA核苷，抑制体外犬粒细胞超氧化物的产生。我们的结论是，心肌缺血前给予AICA核苷增加腺苷浓度，减少心律失常，减少粒细胞聚集，并改善缺血心肌的侧支血流。其中一个有益的机制可能是ATP催化剂产生的腺苷而不是肌苷的增加，从而导致血管舒张和粒细胞抑制。我们提出了一个新的假说，关于调节炎症反应缺血微循环。腺苷，除了它的血管扩张作用，是一种抗损伤的autacoid，连接ATP catalysts抑制粒细胞粘附，微血管阻塞，和超氧阴离子的形成。
Morbidity and mortality from acute coronary artery occlusion may be reduced if local myocardial adenosine concentration is augmented because 1) coronary collateral blood flow during ischemia increases with adenosine infusion, and 2) granulocytes that accumulate in the microcirculation during ischemia are, to a large extent, inhibited by adenosine from generating superoxide anion free radicals, from adhering to vascular endothelium, and from damaging endothelial cells in culture. Using a cultured lymphoblast model system, we found that 5-amino-4-imidazole carboxamide (AICA) riboside enhanced adenosine accumulation during ATP catabolism. Therefore, AICA riboside pretreatment was used in canine myocardium to selectively increase adenosine concentration in the ischemic area during 1 hour of ischemia. At 5 minutes of ischemia, endocardial flow to ischemic myocardium in saline-treated and AICA riboside-treated dogs was 0.06 .+-. 0.03 and 0.34 .+-. 0.11 ml/ming/g, respectively (p < 0.01); flow to nonischemic myocardium was not affected. Ventricular tachycardia and premature ventricular depolarizations were significantly attenuated in the AICA riboside-treated dogs. Blood pressure and heart rate were not affected by AICA riboside. In venous blood from ischemic tissue, adenosine increased from undetectable levels (< 0.01 .mu.M) to 0.22 .+-. 0.08 .mu.M in saline and 1.79 .+-. 0.06 .mu.M in AICA riboside-treated dogs, respectively (p < 0.001). Coronary vein inosine concentrations were greater in saline than in AICA riboside-treated dogs. In separate in vitro studies, AICA riboside did not alter the removal rate of adenosine from canine blood, Indium-labeled granulocyte accumulation was significantly less in ischemic myocardium in AICA riboside-treated compared with saline-treated dogs. In addition, adenosine, but not AICA riboside, inhibited in vitro canine granulocyte superoxide production. We conclude that AICA riboside given before myocardial ischemia augments adenosine concentration, decreases arrhythmias, decreases granulocyte accumulation, and improves collateral flow to ischemic myocardium. One of the beneficial mechanisms could be an increased production of adenosine rather than inosine from ATP catabolism that causes vasodilation and inhibition of granulocytes. We propose a new hypothesis regarding regulation of the inflammatory reaction to ischemia in the microcirculation. Adenosine, in addition to its vasodilator action, is an anti-injury autacoid that links ATP catabolism to inhibition of granulocyte adherence, microvascular obstruction, and superoxide anion formation.