Hayashi Y, Kamibayashi T, Maze M, Yamatodani A, Sumikawa K, Kuro M, Yoshiya I
Department of Anesthesiology, National Cardiovascular Center, Osaka, Japan.
Anesthesiology. 1993 Mar;78(3):524-30. doi: 10.1097/00000542-199303000-00016.
Drugs with a central alpha 2-adrenergic action can increase the threshold for halothane-epinephrine-induced arrhythmias. Recently, imidazoline-preferring receptors were shown to play a significant role in the hypotensive effect of alpha 2-adrenergic agonists containing an imidazole ring in their structure. To address the question of whether the antiarrhythmic property of the alpha 2-adrenergic agonists was caused by activation of alpha 2-adrenoceptors or imidazoline-preferring receptors in the central nervous system, the effect of an imidazoline (atipamezole) and a nonimidazoline (L-659,066 and yohimbine) alpha 2-adrenergic antagonist were examined as etiologic factors in the genesis of halothane-epinephrine-induced arrhythmias in dogs.
Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and for premature ventricular contractions. The arrhythmogenic dose (AD) of epinephrine, defined as the smallest dose producing four or more premature ventricular contractions within a 15-s period, was determined in the presence of atipamezole (an imidazoline compound that acrosses the blood-brain barrier), L-659,066 (a nonimidazoline compound that does not penetrate the blood-brain barrier), and yohimbine (a nonimidazoline compound that passes the blood-brain barrier). These drugs were administered either intravenously or into the cisterna magna to assess the site of action for changes in responsiveness.
Intravenous atipamezole decreased the AD of epinephrine in the dose-dependent fashion. However, neither L-659,066 nor yohimbine, administered peripherally, decreased the AD of epinephrine. Central administration of atipamezole also decreased the AD of epinephrine, while L-659,066, even if administered centrally, did not affect the AD of epinephrine in the presence of halothane.
Because the imidazoline ring-containing alpha 2-adrenergic antagonist (atipamezole) potentiated the halothane-epinephrine-induced arrhythmias and the nonimidazole alpha 2-adrenergic antagonist (L-659,066 and yohimbine) did not, it is possible that the imidazoline-preferring, rather than the alpha 2-adrenergic, receptor is responsible for the antiarrhythmic property of alpha 2-adrenergic agonists.
具有中枢α2 - 肾上腺素能作用的药物可提高氟烷 - 肾上腺素诱导的心律失常阈值。最近研究表明，咪唑啉优先受体在结构中含有咪唑环的α2 - 肾上腺素能激动剂的降压作用中起重要作用。为探讨α2 - 肾上腺素能激动剂的抗心律失常特性是由中枢神经系统中α2 - 肾上腺素能受体还是咪唑啉优先受体的激活所致，研究了一种咪唑啉（阿替美唑）和两种非咪唑啉（L - 659,066和育亨宾）α2 - 肾上腺素能拮抗剂作为犬氟烷 - 肾上腺素诱导心律失常发生的病因因素的作用。
成年杂种犬用氟烷（1.3%）麻醉，连续监测体动脉压和室性早搏。在存在阿替美唑（一种能透过血脑屏障的咪唑啉化合物）、L - 659,066（一种不能穿透血脑屏障的非咪唑啉化合物）和育亨宾（一种能透过血脑屏障的非咪唑啉化合物）的情况下，确定肾上腺素的致心律失常剂量（AD），即15秒内产生四次或更多次室性早搏的最小剂量。这些药物通过静脉注射或注入小脑延髓池，以评估反应性变化的作用部位。
静脉注射阿替美唑以剂量依赖方式降低肾上腺素的AD。然而，外周给予L - 659,066和育亨宾均未降低肾上腺素的AD。中枢给予阿替美唑也降低肾上腺素的AD，而L - 659,066即使中枢给药，在氟烷存在时也不影响肾上腺素的AD。
由于含咪唑啉环的α2 - 肾上腺素能拮抗剂（阿替美唑）增强氟烷 - 肾上腺素诱导的心律失常，而非咪唑啉α2 - 肾上腺素能拮抗剂（L - 659,066和育亨宾）则无此作用，因此可能是咪唑啉优先受体而非α2 - 肾上腺素能受体介导了α2 - 肾上腺素能激动剂的抗心律失常特性。
