Headrick J, Willis R J
Division of Science and Technology, Griffith University, Queensland, Australia.
Pflugers Arch. 1988 Oct;412(6):618-23. doi: 10.1007/BF00583763.
The role of adenosine as a mediator of the bradycardia associated with graded global ischaemia in rat heart was examined. Hearts were perfused at 37 degrees C in the isovolumic mode with Krebs-bicarbonate medium at 12.0 ml/min/g. After equilibration, the coronary flow was reduced to 0.5, 2.5, or 5.0 ml/min/g for 20 min. Effluent was collected and assayed for adenosine and inosine by HPLC. Heart rate was measured and bipolar electrograms were obtained in severely ischaemic hearts. Basal adenosine release was 124 +/- 15 pmol/min/g. Adenosine release increased by approximately 50% in hearts perfused at 5.0 ml/min/g. In hearts perfused at 2.5 and 0.5 ml/min/g, adenosine release increased by approximately 1300 and 2300% respectively. The pattern of adenosine release at 0.5 and 2.5 ml/min/g was phasic, with adenosine release rate increasing to a maximum after about 10 min then dropping to values slightly higher than initial values. Ischaemia produced significant bradycardia and first degree AV block. Adenosine antagonism with 5 micron 8-phenyltheophylline blocked up to 25% of this bradycardia and significantly reduced the conduction delay. Adenosine release rate correlated closely with that component of heart rate slowing which was inhibited by 8-phenyltheophylline. It is concluded that adenosine released during graded global ischaemia mediates up to a quarter of the associated bradycardia. The effect of adenosine is phasic. Adenosine acts primarily to depress the sinus pacemaker. First degree AV block also occurs. These effects were only apparent at coronary flow rates below 5.0 ml/min/g.
研究了腺苷在大鼠心脏分级全心缺血相关心动过缓中的介导作用。心脏在37℃下以等容模式用碳酸氢盐 Krebs 培养基以12.0 ml/min/g 的速度进行灌注。平衡后，冠状动脉血流量分别降至0.5、2.5或5.0 ml/min/g 并持续20分钟。收集流出液，通过高效液相色谱法测定腺苷和肌苷。测量心率并在严重缺血的心脏中获取双极心电图。基础腺苷释放量为124±15 pmol/min/g。在以5.0 ml/min/g 灌注的心脏中，腺苷释放量增加了约50%。在以2.5和0.5 ml/min/g 灌注的心脏中，腺苷释放量分别增加了约1300%和2300%。在0.5和2.5 ml/min/g 时腺苷释放模式呈阶段性，腺苷释放速率在约10分钟后增加至最大值，然后降至略高于初始值的值。缺血导致显著的心动过缓和一度房室传导阻滞。用5微米8-苯基茶碱进行腺苷拮抗可阻断高达25%的这种心动过缓，并显著减少传导延迟。腺苷释放速率与被8-苯基茶碱抑制的心率减慢成分密切相关。得出的结论是，分级全心缺血期间释放的腺苷介导了高达四分之一的相关心动过缓。腺苷的作用是阶段性的。腺苷主要作用于抑制窦房结起搏器。也会发生一度房室传导阻滞。这些效应仅在冠状动脉血流量低于5.0 ml/min/g 时才明显。
