Gewirtz H, Brautigan D L, Olsson R A, Brown P, Most A S
Circ Res. 1983 Jul;53(1):42-51. doi: 10.1161/01.res.53.1.42.
The purpose of this study was to test the hypothesis that adenosine is required to maintain arteriolar vasodilation distal to a severe coronary stenosis. Eight closed-chest conscious pigs were prepared by placing a 7.5-mm long stenosis (82% lumenal diameter reduction) in the proximal left anterior descending coronary artery. Regional myocardial blood flow (microsphere technique) was measured at control 1, after 10 minutes of intracoronary infusion of adenosine deaminase (7-10 U/kg per min) distal to the stenosis, and 20-30 minutes after stopping adenosine deaminase infusion. Studies with 125I-labeled adenosine deaminase were conducted in six additional pigs to document the extent to which infused adenosine deaminase penetrated the interstitial space. 125I-labeled adenosine deaminase was infused for 10 minutes (10-11 U/kg per min) into the left anterior descending coronary artery. Calculated interstitial fluid concentrations of adenosine deaminase ranged between 71 and 272 U/ml and were at least one order of magnitude greater than that required to deaminate all the adenosine which would be released into the interstitium in response to 15-30 seconds of coronary occlusion. In the primary group of animals (n = 8), endocardial flow (ml/min per g) distal to stenosis at control 1 (1.15 +/- 0.33) was reduced vs. endocardial flow in the nonobstructed circumflex zone (1.59 +/- 0.38, P less than 0.05). Flows in epicardial layers were comparable at control 1 (distal zone = 1.40 +/- 0.36 vs. circumflex zone = 1.45 +/- 0.41). Distal zone endocardial and epicardial flows did not change vs. control 1 in response to infusion of adenosine deaminase. However, the distal: circumflex epicardial flow ratio declined vs. control 1 (0.98 +/- 0.14) during adenosine deaminase infusion (0.87 +/- 0.17, P less than 0.05). The distal:circumflex endocardial flow ratio during adenosine deaminase (0.72 +/- 0.20) was unchanged vs. control 1 (0.76 +/- 0.22) but was less than control 2 (0.80 +/- 0.18, P less than 0.05). Thus, destruction of all or most interstitial adenosine caused only slight relative reduction in regional myocardial blood flow distal to a severe coronary artery stenosis. Accordingly, adenosine contributes only modestly to maintenance of arteriolar vasodilation in this setting or else its absence is almost fully compensated for by another mechanism(s).
腺苷是维持严重冠状动脉狭窄远端小动脉血管舒张所必需的。通过在左前降支冠状动脉近端放置一个7.5毫米长的狭窄（管腔直径减少82%），制备了八只闭胸清醒猪。在对照1时、在狭窄远端冠状动脉内输注腺苷脱氨酶（7 - 10 U/kg每分钟）10分钟后以及停止腺苷脱氨酶输注20 - 30分钟后，测量局部心肌血流量（微球技术）。在另外六只猪中进行了用125I标记的腺苷脱氨酶的研究，以记录输注的腺苷脱氨酶渗透到间质空间的程度。将125I标记的腺苷脱氨酶以10分钟（10 - 11 U/kg每分钟）的时间输注到左前降支冠状动脉中。计算出的腺苷脱氨酶间质液浓度在71至272 U/ml之间，并且比使因冠状动脉闭塞15 - 30秒而释放到间质中的所有腺苷脱氨所需的浓度至少高一个数量级。在第一组动物（n = 8）中，对照1时狭窄远端的心内膜血流量（毫升/分钟每克）（1.15±0.33）与无阻塞的回旋支区域的心内膜血流量（1.59±0.38，P<0.05）相比降低。在对照1时，心外膜层的血流量相当（远端区域 = 1.40±0.36与回旋支区域 = 1.45±0.41）。在输注腺苷脱氨酶期间，远端区域的心内膜和心外膜血流量与对照1相比没有变化。然而，在腺苷脱氨酶输注期间，远端:回旋支心外膜血流量比值与对照1相比下降（0.98±0.14）（0.87±0.17，P<0.05）。腺苷脱氨酶期间的远端:回旋支心内膜血流量比值（0.72±0.20）与对照1（0.76±0.22）相比没有变化，但低于对照2（0.80±0.18，P<0.05）。因此，全部或大部分间质腺苷的破坏仅导致严重冠状动脉狭窄远端局部心肌血流量出现轻微的相对减少。因此，在这种情况下，腺苷对维持小动脉血管舒张的贡献不大，或者其缺失几乎完全由另一种机制补偿。
