Wesley R C, Belardinelli L
Circ Res. 1985 Oct;57(4):517-31. doi: 10.1161/01.res.57.4.517.
The present study was undertaken to demonstrate and characterize potentiation of ventricular overdrive suppression by adenosine. To substantiate that adenosine has an enhanced effect on overdrive suppression, it would be necessary to demonstrate that adenosine increases pause duration independent of slowing spontaneous pre-drive rate. In isolated perfused guinea pig hearts with surgically induced complete atrioventricular block, the effect of adenosine (2-20 microM) on pause duration was compared to two alternative means of slowing the pre-drive rate, i.e., hypothermia (28.0 degrees C to 34.0 degrees C) and cesium chloride (0.3-1.0 mM). The slope value of the linear regression line describing the relationship between pre-drive cycle length and pause duration for adenosine (15.8) was significantly greater than control (1.7), hypothermia (1.7), and cesium chloride (5.4). The competitive adenosine antagonist, aminophylline (60 microM), when infused at the initiation of overdrive during adenosine administration, significantly reduced the effect of adenosine on pause duration by 72.9 +/- 4.2% (mean +/- SEM). The reduction in pause duration by aminophylline was specific for adenosine and did not occur under control conditions or during cesium chloride administration. During hypoxia, aminophylline and adenosine deaminase, when infused at the initiation of overdrive, caused 72.3 +/- 5.6 and 63.3 +/- 6.1% reductions in pause duration, respectively. Endogenous adenosine levels rose significantly with hypoxia (1,687 +/- 202 vs. 36 +/- 4 pmol/min per g during normoxia) and increased significantly further during hypoxic overdrive (3,004 +/- 323 pmol/min per g). In isolated guinea pig Purkinje fibers (n = 4), adenosine (20 microM) increased pause duration by 73.6 +/- 9.9% while only minimally affecting the pre-drive cycle length (7.6 +/- 3.8%). These fibers, when stimulated at 1.5 Hz, also displayed an adenosine-induced reduction in action potential duration at 90% repolarization (16 +/- 2 msec). In addition, we demonstrated that adenosine had an enhanced effect on pause duration in the presence of ouabain (1 microM)-induced attenuation of overdrive suppression. Thus, in isolated Purkinje fibers, it is unlikely that the potentiating effect of adenosine on pause duration, which is independent of its chronotropic effect, is mediated via an enhancement of sodium potassium adenosine triphosphatase pump activity. The effect of adenosine is likely to be secondary to a direct action on outward potassium conductance.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究旨在证明并描述腺苷对心室超速抑制的增强作用及特征。为证实腺苷对超速抑制有增强作用，有必要证明腺苷能增加停顿持续时间，且与减慢自发驱动前速率无关。在手术诱导完全性房室传导阻滞的离体灌注豚鼠心脏中，将腺苷（2 - 20微摩尔）对停顿持续时间的影响与另外两种减慢驱动前速率的方法进行比较，即低温（28.0℃至34.0℃）和氯化铯（0.3 - 1.0毫摩尔）。描述腺苷（15.8）驱动前周期长度与停顿持续时间关系的线性回归线斜率值显著大于对照组（1.7）、低温组（1.7）和氯化铯组（5.4）。竞争性腺苷拮抗剂氨茶碱（60微摩尔）在腺苷给药期间超速驱动开始时注入，可使腺苷对停顿持续时间的影响显著降低72.9±4.2%（平均值±标准误）。氨茶碱使停顿持续时间缩短对腺苷具有特异性，在对照条件下或氯化铯给药期间未出现。在缺氧期间，氨茶碱和腺苷脱氨酶在超速驱动开始时注入，分别使停顿持续时间缩短72.3±5.6%和63.3±6.1%。内源性腺苷水平在缺氧时显著升高（1687±202对常氧时的36±4皮摩尔/分钟每克），在缺氧超速驱动期间进一步显著升高（3004±323皮摩尔/分钟每克）。在离体豚鼠浦肯野纤维（n = 4）中，腺苷（20微摩尔）使停顿持续时间增加73.6±9.9%，而对驱动前周期长度影响极小（7.6±3.8%）。这些纤维在1.5赫兹刺激时，在90%复极化时也表现出腺苷诱导的动作电位持续时间缩短（16±2毫秒）。此外，我们证明在哇巴因（1微摩尔）诱导超速抑制减弱的情况下，腺苷对停顿持续时间仍有增强作用。因此，在离体浦肯野纤维中，腺苷对停顿持续时间的增强作用与其变时作用无关，不太可能是通过增强钠钾腺苷三磷酸酶泵活性介导的。腺苷的作用可能是对外向钾电导直接作用的结果。（摘要截短至400字）
