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

短暂的心肌缺血可导致心脏交感神经一过性功能障碍。肿瘤坏死因子-a是一种多功能细胞因子，在心肌缺血和再灌流过程中也会产生。虽然肿瘤坏死因子-α被认为是中枢神经系统中的一种神经营养因子，但其在心脏神经顿抑中的保护作用尚未确定。我们检验了一种假说，即肿瘤坏死因子-a可减轻交感神经冠状动脉收缩的缺血后减少。用α-氯醛糖麻醉蒙古犬，记录心率(HR)、动脉压(AP)、LV-DP-dt、节段长度百分比(%SL)、LAD和Lcx冠脉血流速度(CDV)。双侧迷走神经切断，心得安阻断b-肾上腺素能，阻断LAD 15min后再灌流。采用双侧锁骨下动脉窦电刺激方法，评价交感神经刺激对冠脉阻力(D%CVR)…的影响比较15分钟LAD封堵术松解前后的变化。在冠状动脉结扎前15min开始冠脉内注射肿瘤坏死因子-α(6ug/kg/min，n=6)或赋形剂(n=5)，再灌流后5min开始给药。另一组冠脉内注射抗肿瘤坏死因子-α抗体(60nl/kg/mm，n=6)或赋形剂(n=5)，在LAD结扎7min前和结扎7min后，也计算出*%CVR。结果：1)交感神经刺激使LAD和Lcx床冠脉阻力一过性增加。再灌流前(40±8%，MSE)和再灌流后15分钟(38±8%)，应用肿瘤坏死因子-α的犬LAD床上的CVR差异无统计学意义。这与使用Vehicle的犬LAD抵抗的变化形成对比(再灌流前为38×5%，再灌流后为162%；p&lt；0.05)。2)左前降支结扎7min对犬LAD床区CVR无明显影响，而抗肿瘤坏死因子-α抗体可使其降低(再灌流前为38±5%，再灌流后为19×8%；P<0.05)，提示肿瘤坏死因子-α对交感神经支配所致的缺血后神经顿抑有保护作用。较少

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