Daugherty A, Frayn K N, Redfern W S, Woodward B
Br J Pharmacol. 1986 Jan;87(1):265-77. doi: 10.1111/j.1476-5381.1986.tb10180.x.
The role of catecholamines in the production of ischaemia-induced ventricular arrhythmias in vivo and in vitro was studied using coronary artery ligation in the rat. Increases in plasma catecholamine concentrations during coronary artery ligation in pentobarbitone-anaesthetized animals were prevented by either acute adrenalectomy or chronic adrenal demedullation, but these procedures did not protect against the occurrence of ventricular arrhythmias. Thus plasma catecholamines were not obligatory mediators of arrhythmogenesis. Three protocols were used in vitro to evaluate the possible influence of intramyocardial release of noradrenaline, produced by the local conditions of ischaemia, on the production of ventricular arrhythmias. During coronary artery ligation in isolated perfused hearts, no enhanced output of 3H could be detected from [3H]-noradrenaline loaded hearts, even in the presence of inhibitors of catecholamine uptake processes, although washout of lactate from ischaemic regions was readily demonstrable. Both optical isomers of propranolol were equally effective in reducing the incidence of arrhythmias, implying a non-specific effect, since the (+)-isomer possesses considerably less beta-adrenoceptor blocking activity. The equipotency of optical isomers of propranolol combined with a lack of effect of atenolol suggested that arrhythmia production was not a consequence of beta-adrenoceptor stimulation. The alpha-adrenoceptor blockers phentolamine and prazosin, both exerted antiarrhythmic actions of similar potency, but phenoxybenzamine and trimazosin had no significant effects. An evaluation of the pharmacological properties of the alpha-adrenoceptor blockers showed that those drugs which had demonstrable local anaesthetic properties also exerted significant antiarrhythmic effects. No relationship was found between potency of alpha-adrenoceptor blockade and antiarrhythmic efficacy. The overall conclusion from these multifaceted approaches was that catecholamines were not necessary mediators of the early phase of ventricular arrhythmias in the rat.
利用大鼠冠状动脉结扎术，研究了儿茶酚胺在体内和体外缺血诱导的室性心律失常产生中的作用。在戊巴比妥麻醉的动物中进行冠状动脉结扎时，急性肾上腺切除术或慢性肾上腺髓质剥脱术可防止血浆儿茶酚胺浓度升高，但这些操作并不能预防室性心律失常的发生。因此，血浆儿茶酚胺不是心律失常发生的必需介质。采用三种体外实验方案来评估局部缺血条件下心肌内去甲肾上腺素释放对室性心律失常产生的可能影响。在离体灌注心脏的冠状动脉结扎过程中，即使存在儿茶酚胺摄取过程抑制剂，从[3H] - 去甲肾上腺素加载的心脏中也检测不到3H的输出增加，尽管缺血区域乳酸的洗脱很容易证明。普萘洛尔的两种光学异构体在降低心律失常发生率方面同样有效，这意味着是非特异性作用，因为(+) - 异构体的β - 肾上腺素受体阻断活性要低得多。普萘洛尔光学异构体的等效性以及阿替洛尔缺乏作用表明心律失常的产生不是β - 肾上腺素受体刺激的结果。α - 肾上腺素受体阻滞剂酚妥拉明和哌唑嗪都发挥了相似效力的抗心律失常作用，但酚苄明和曲马唑嗪没有显著作用。对α - 肾上腺素受体阻滞剂药理特性的评估表明，那些具有明显局部麻醉特性的药物也发挥了显著的抗心律失常作用。未发现α - 肾上腺素受体阻断效力与抗心律失常疗效之间的关系。这些多方面研究方法得出的总体结论是，儿茶酚胺不是大鼠室性心律失常早期阶段的必需介质。
