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

短暂的心肌缺血可引起心脏交感神经的一过性功能障碍。肿瘤坏死因子-a （Tumor necrotizing factor -a, TNF-a）是一种多功能细胞因子，在心肌缺血和再灌注过程中也会产生。虽然据报道TNF-a是中枢神经系统的一种神经营养因子，但TNF-a在心脏神经昏迷中的保护作用尚未确定。我们检验了TNF-a减轻交感冠状动脉收缩缺血后减少的假设。用a-氯氯蔗糖麻醉杂种狗，记录心率（HR）、动脉压（AP）、左室dP / dt、%节段长度（%SL）、LAD和LCX冠状动脉血流速度（多普勒）。双侧迷走神经切开术和心得安阻断b-肾上腺素能后，LAD闭塞15分钟后再灌注。对双侧锁骨下ansa进行电刺激，评估冠脉对交感刺激阻力的百分比变化（D%CVR）。冠脉闭塞前15分钟至再灌注后5分钟开始冠脉内注射TNF-a （6 ug/kg/min, n=6）或载药（n=5），另一只冠脉内注射抗TNF-a抗体（60 nl/kg/mm, n=6）或载药（n=5）的狗，在LAD闭塞解除7分钟前后也估计了*%CVR。结果：1)交感刺激在LAD和LCX床均引起冠脉阻力一过性升高。TNF-a治疗犬LAD床前（40*8%，MSE）和再灌注后15 min（38*8%）的CVR *%无显著差异。这与载药犬的LAD阻力变化（再灌注前38*5%，再灌注后162%，p<0.05）形成对比。2)溶栓7 min后LAD床*%CVR不受影响，抗tnf -a抗体降低（再灌注前38*5%，再灌注后19* 8%，p<0.05）。我们得出结论，TNF-a保护交感冠状神经支配的缺血性神经休克。少

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