Contribution of protein kinases in the ischemic-induced dysfunction of cardiac sympathic innervation

蛋白激酶在缺血引起的心脏交感神经支配功能障碍中的作用

• 批准号: 08670755
• 负责人: ABE Toyohiko
• 金额: $ 1.47万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670755/
• 关键词: TNF-alpha; neural stunning; 心臓交感神経; 心筋虚血; hydrocortisone; nerve growth factor; tumor necrosis factor-α; 副腎皮質ステロイド

A brief period of myocardial ischemia is capable of producing transient dysfunction of cardiac sympathetic innervation. Tumor necrotizing facter-a (TNF-a) is a multifunctional cytokine that is also produced during myocardial ischemia and reperfusion. While TNF-a is reported to be a neurotrophic factor in the central nervous system, the protective role of TNF-a in cardiac neural stunning has not been determined. We examined the hypothesis that TNF-a attenuates post-ischemic reductions in sympathetic coronary constriction. Mongreldogs were anesthetized with a-chloralose and instrumented for recordings of heart rate (HR), arterial pressure (AP), LV dP dt, % segment length (%SL) and LAD and LCX coronary flow velocities (Doppler). After bilateral vagotomy and b-adrenergic blockade by propranolol, LAD was occluded for 15 min followed by reperfusion. Bilateral electrical stimulation of ansa subclavia was performed to evaluate % change in coronary resistance to sympathetic stimulation (D%CVR) … More before and after release of 15 min LAD occlusion. Intracoronary administration of TNF-a (6 ug/kg/min, n=6) or vehicle (n=5) was started 15 min before coronary occlusion to 5 min after reperfusion, In another dogs with intracoronary administration of anti-TNF-a antibody (60 nl/kg/mm, n=6) or vehicle (n=5), *%CVR was also estimated before and after release of 7 min LAD occlusion.Results : 1) Sympathetic stimulation produced transient increase in coronary resistance in both LAD and LCX beds. *%CVR in the LAD bed before (40*8%, MSE) and 15 min after reperfusion (38*8%) was not different in dogs treated with TNF-a . This contrasts with the change in LAD resistance from dogs with vehicle (38*5% before and 162% after reperfusion ; p<0.05). 2) *%CVR in the LAD bed after release of 7 min LAD occlusion was not affected in dogs with vehicle, while it was decreased with anti-TNF-a antibody(38*5% before and 19* 8% after reperfusion ; p<0.05).We conclude that TNF-a protects against post-ischemic neural stunning of sympathetic coronary innervation. Less

短暂的心肌缺血能够产生短暂的心脏交感神经支配功能障碍。肿瘤坏死因子-a (TNF-a) 是一种多功能细胞因子，在心肌缺血和再灌注期间也会产生。 TNF-a 是中枢神经系统中的神经营养因子，但 TNF-a 在心脏神经击晕中的保护作用尚未确定，我们检验了 TNF-a 减弱缺血后的假设。用α-氯醛糖麻醉杂种狗，并用仪器记录心率（HR）、动脉压（AP）、LV dP dt、%节段长度（%SL）以及LAD和LCX冠状动脉血流速度（多普勒）。双侧迷走神经切断术和普萘洛尔β-肾上腺素能阻断后，闭塞LAD 15分钟，然后进行双侧锁骨下电刺激，以评估冠状动脉对交感神经刺激的抵抗力 (D%CVR) 的变化百分比……更多 在冠状动脉内给予 TNF-a（6 ug/kg/min）之前和之后。 ，n = 6)或媒介物(n = 5)在冠状动脉闭塞前15分钟至再灌注后5分钟开始，在另一只冠状动脉内施用抗TNF-α抗体的狗中(60 nl/kg/mm, n=6) 或媒介物 (n=5)，*%CVR 也在释放 7 分钟 LAD 闭塞之前和之后进行估计。结果：1) 交感神经刺激使两者的冠状动脉阻力短暂增加* 在用 TNF-α 治疗的狗中，LAD 床在再灌注前 (40*8%，MSE) 和 15 分钟后 (38*8%) 的 CVR 没有差异。这与使用载体的狗的 LAD 抵抗力的变化形成对比（再灌注前为 38*5%，再灌注后为 162%；p<0.05）*释放 7 分钟 LAD 闭塞后，LAD 床中的 CVR 不受影响。使用媒介物的狗，而使用抗TNF-a抗体则降低（再灌注前38*5%，再灌注后19*8%；p<0.05）。我们得出结论： TNF-a 可防止交感冠状动脉神经支配的缺血后神经震颤。

项目成果

Toyohiko Abe: "Protective role of nerve growth factor against postischemic dysfunction of sympathetic coronary innervation" Circulation. 95(1). 213-220 (1997)

Toyohiko Abe：“神经生长因子对交感冠状动脉神经支配缺血后功能障碍的保护作用”循环。

Toyohiko Abe: "Role of adenosine receptor subtypes in neural stunning of sympathefic coronary innervation" Am.J.Physiol.272(Jan). H25-H34 (1997)

Toyohiko Abe：“腺苷受体亚型在交感冠状动脉神经支配的神经震慑中的作用”Am.J.Physiol.272（一月）。

Toyohiko Abe: "Role of adenosine receptor subtypes in neural stunning of sympathetic coronary innervation" Am.J.Physiol. 272(Jan). H25-H34 (1997)

Toyohiko Abe：“腺苷受体亚型在交感冠状动脉神经支配的神经震慑中的作用”Am.J.Physiol。

Toyohiko Abe: "Proteetive role of nerve growth factor against postischemic dysfunction of sympathetic coronary innervation" Circulation. 95(1). 213-220 (1997)

Toyohiko Abe：“神经生长因子对交感冠状动脉神经支配缺血后功能障碍的保护作用”循环。