Cai John J, Morgan Donald A, Haynes William G, Martins James B, Lee Hon-Chi
Department of Internal Medicine, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City 52242, USA.
Am J Physiol Heart Circ Physiol. 2002 Dec;283(6):H2606-11. doi: 10.1152/ajpheart.00156.2002.
We previously reported that alpha(2)-adrenergic receptor (alpha(2)-AR) stimulation in Purkinje fibers in vitro prolongs action potential duration and suppresses beta-adrenergic-induced delayed afterdepolarizations and sustained triggered activities. We examined the effects of alpha(2)-AR stimulation on reperfusion-induced ventricular arrhythmias [ventricular tachycardia/ventricular fibrillation (VT/VF)] in vivo. Arterial blood pressure, heart rate, surface electrocardiogram, and renal sympathetic nerve activities were recorded simultaneously in Sprague-Dawley rats. The incidence of VT/VF was 87.5% for controls, 50% for the beta-blocker group, 72% for the alpha(1)-blocker group, and 12.5% for the alpha(1) + beta-blockers group (unopposed alpha(2)-adrenergic activation). Direct alpha(2)-AR stimulation with UK-14304 also prevented VT/VF. These effects were reversed by the alpha(2)-adrenergic antagonist yohimbine. Increases in renal sympathetic nerve activity were associated with left anterior descending coronary artery ligation and reperfusion (33 +/- 1.5 and 62 +/- 1.7% over baseline, respectively) in controls. Similar patterns were observed among all experimental groups irrespective of the incidence of VT/VF on reperfusion. We conclude that alpha(2)-AR stimulation has a potent antiarrhythmic effect on ischemia-reperfusion-induced VT/VF in vivo and that this effect is not centrally mediated.
我们之前报道过，体外刺激浦肯野纤维中的α₂ - 肾上腺素能受体（α₂ - AR）可延长动作电位时程，并抑制β - 肾上腺素能诱导的延迟后去极化和持续性触发活动。我们研究了α₂ - AR刺激对体内再灌注诱导的室性心律失常[室性心动过速/心室颤动（VT/VF）]的影响。在Sprague - Dawley大鼠中同时记录动脉血压、心率、体表心电图和肾交感神经活动。对照组VT/VF的发生率为87.5%，β - 阻滞剂组为50%，α₁ - 阻滞剂组为72%，α₁ + β - 阻滞剂组（α₂ - 肾上腺素能无对抗激活）为12.5%。用UK - 14304直接刺激α₂ - AR也可预防VT/VF。这些作用可被α₂ - 肾上腺素能拮抗剂育亨宾逆转。在对照组中，肾交感神经活动的增加与左前降支冠状动脉结扎和再灌注有关（分别比基线升高33±1.5%和62±1.7%）。在所有实验组中均观察到类似模式，与再灌注时VT/VF的发生率无关。我们得出结论，α₂ - AR刺激对体内缺血 - 再灌注诱导的VT/VF具有强大的抗心律失常作用，且该作用并非由中枢介导。
