Wainwright C L, Parratt J R
Department of Physiology and Pharmacology, University of Strathclyde, Royal College, Glasgow, United Kingdom.
Cardiovasc Res. 1993 Jan;27(1):84-9. doi: 10.1093/cvr/27.1.84.
Adenosine has previously been shown to protect against ischaemia induced ventricular arrhythmias. The aim of this study was to determine whether stimulation of A1 adenosine receptors with a selective agonist also protects against arrhythmias, and to attempt to elucidate the underlying mechanisms.
Large White/Welsh Landrace cross breed domestic pigs (25-40 kg) subjected to left anterior descending coronary artery occlusion were used. R-PIA [R(-)N6-(2-phenylisopropyl) adenosine; 5 micrograms.kg-1] was given prior to coronary artery occlusion and the effects on haemodynamic variables and early ischaemic arrhythmias in the absence and presence of right atrial pacing were studied. The three experimental groups were: solvent controls, n = 10; R-PIA without pacing, n = 10; R-PIA with atrial pacing, n = 10. Ex vivo assessment of platelet aggregation was also performed to determine any inhibitory effects of R-PIA on platelets.
Administration of R-PIA without atrial pacing reduced the total number of ventricular ectopic beats induced by coronary occlusion, from 326(SEM 71) in controls to 121(30) (p < 0.05) and the incidence of ventricular fibrillation from 70% to 20% (p < 0.05). At the dose used, R-PIA reduced heart rate from 102(7) to 74(3) beats.min-1, with a consequent reduction in mean arterial blood pressure from 95(4) to 81(3) mm Hg. Atrial pacing following drug administration, at a rate of 109(5) beats.min-1, restored blood pressure and abolished the antiarrhythmic effects of R-PIA. Drug intervention had no effect on either ex-vivo platelet aggregation or coronary sinus oxygen content, suggesting a lack of activity at A2 adenosine receptors.
An A1 adenosine receptor agonist exerts a marked protection against ischaemia induced ventricular arrhythmias and fibrillation in pigs. The reversal of this effect by restoring heart rate suggests that the drug induced bradycardia may be important in the antiarrhythmic action of R-PIA, possibly via an anti-ischaemic effect.
先前已证明腺苷可预防缺血诱导的室性心律失常。本研究的目的是确定用选择性激动剂刺激A1腺苷受体是否也能预防心律失常，并试图阐明其潜在机制。
使用大白猪/威尔士长白猪杂交的家猪（25 - 40千克），使其左前降支冠状动脉闭塞。在冠状动脉闭塞前给予R - PIA [R(-)N6-(2-苯异丙基)腺苷；5微克·千克-1]，并研究其在有无右心房起搏情况下对血流动力学变量和早期缺血性心律失常的影响。三个实验组分别为：溶剂对照组，n = 10；未起搏的R - PIA组，n = 10；起搏的R - PIA组，n = 10。还进行了体外血小板聚集评估，以确定R - PIA对血小板的任何抑制作用。
未进行心房起搏时给予R - PIA可使冠状动脉闭塞诱导的室性早搏总数从对照组的326（标准误71）减少至121（30）（p < 0.05），室颤发生率从70%降至20%（p < 0.05）。在所使用的剂量下，R - PIA使心率从102（7）降至74（3）次·分钟-1，平均动脉血压随之从95（4）降至81（3）毫米汞柱。给药后以109（5）次·分钟-1的速率进行心房起搏可恢复血压并消除R - PIA的抗心律失常作用。药物干预对体外血小板聚集或冠状窦氧含量均无影响，表明在A2腺苷受体处缺乏活性。
A1腺苷受体激动剂对猪缺血诱导的室性心律失常和颤动具有显著的保护作用。通过恢复心率使这种作用逆转表明，药物诱导的心动过缓可能在R - PIA的抗心律失常作用中起重要作用，可能是通过抗缺血作用实现的。
