Vatner D E, Vatner S F
Cardiovascular and Pulmonary Research Institute, Allegheny University of the Health Sciences, Pittsburgh, PA 15212, USA.
Mol Cell Biochem. 1998 Sep;186(1-2):131-7.
A dual approach was employed to study beta-adrenergic receptor signal transduction in post ischemic (stunned) myocardium, examining physiological interventions in awake, chronically instrumented pigs and biochemical, cellular mechanisms in sarcolemmal preparations from the stunned hearts using the contralateral non-ischemic zone as a control. Ten min of coronary artery occlusion (CAO) and 30 min coronary artery reperfusion (CAR) resulted in depressed posterior wall-thickening (myocardial stunning). Isoproterenol increased transmural wall thickening more in stunned myocardium than in non-ischemic myocardium. In contrast, the responses of wall thickening to forskolin, actually decreased during stunning compared with control. NKH 477, a water soluble forskolin derivative, that does not activate cardiac nerves, increased wall thickening in non-ischemic tissue similarly to the effects on stunned myocardium. Increasing cardiac neural tone reflexly with inferior venal caval occlusion (IVCO) elicited similar results to forskolin, i.e., stunned myocardium responded with less of an increase in wall thickening as compared with non-ischemic myocardium. Beta-adrenergic receptor density, as determined with 125I-cyanopindolol binding, was significantly increased in stunned subendocardium and subepicardium compared with respective values in non-ischemic myocardium. There were no differences in the response of adenylyl cyclase to isoproterenol in stunned and non-ischemic myocardium. The enhanced responsiveness of the beta-adrenergic receptor to isoproterenol stimulation in stunned myocardium corresponded to the increase in beta-adrenergic receptor density. The combination of enhanced responses to isoproterenol, and decreased responses to forskolin and to IVCO and preserved responsiveness to NKH 477, suggest that stunned myocardium is characterized by transient sympathetic neural stunning. The enhanced sensitivity to beta-adrenergic receptor stimulation has important clinical implications, both in terms of therapy of stunned myocardium and detection of stunned and/or hibernating myocardium, i.e., low dose dobutamine echocardiography.
采用了一种双重方法来研究缺血后（顿抑）心肌中的β-肾上腺素能受体信号转导，即对清醒的、长期植入仪器的猪进行生理干预，并以对侧非缺血区作为对照，研究顿抑心脏肌膜制剂中的生化和细胞机制。冠状动脉闭塞（CAO）10分钟和冠状动脉再灌注（CAR）30分钟导致后壁增厚降低（心肌顿抑）。异丙肾上腺素在顿抑心肌中比在非缺血心肌中更能增加透壁增厚。相比之下，与对照组相比，在顿抑期间壁增厚对福斯可林的反应实际上降低了。NKH 477是一种不激活心脏神经的水溶性福斯可林衍生物，它在非缺血组织中增加壁增厚的效果与对顿抑心肌的作用相似。通过下腔静脉闭塞（IVCO）反射性增加心脏神经张力产生了与福斯可林相似的结果，即与非缺血心肌相比，顿抑心肌壁增厚的增加较少。用125I-氰吲哚洛尔结合法测定的β-肾上腺素能受体密度，与非缺血心肌中的相应值相比，在顿抑的心内膜下和心外膜下显著增加。在顿抑和非缺血心肌中，腺苷酸环化酶对异丙肾上腺素的反应没有差异。顿抑心肌中β-肾上腺素能受体对异丙肾上腺素刺激的反应增强与β-肾上腺素能受体密度的增加相对应。对异丙肾上腺素反应增强、对福斯可林和IVCO反应降低以及对NKH 477反应保持不变，这些因素共同表明顿抑心肌的特征是短暂的交感神经顿抑。对β-肾上腺素能受体刺激的敏感性增强具有重要的临床意义，无论是在顿抑心肌的治疗方面，还是在顿抑和/或冬眠心肌的检测方面，即低剂量多巴酚丁胺超声心动图检查。
