心脏交感神经顿抑机制的初步研究

The pilot study on the mechanism of neuronal stunning in the postischemic rat heart

目的 :探讨缺血后大鼠心脏交感神经顿抑现象及其内在机制。方法 :运用电场刺激 (频率 6Hz,电压 5V ,脉宽 2ms,持续 1min)诱导离体灌注鼠心去甲肾上腺素 (NA)胞裂释放 ,并通过自身前后两次刺激比较(S2 ∶S1)以判断心脏交感神经末梢NA的释放状况。结果 :①大鼠心脏缺血 30min后恢复灌注其交感神经末梢NA的释放受到明显抑制 (neuronalstunning ,神经顿抑 ) ,并随复灌时间的延长 (第 1、5、30分钟 ) ,交感神经顿抑得到逐渐恢复 (S2 /S1:0 .2 3± 0 .0 31,0 .4 1± 0 .0 4 3和 0 .6 2± 0 .0 5 ,均P <0 .0 1) ;②腺苷受体阻滞剂 8 苯基茶碱使缺血后大鼠心脏交感神经末梢NA的释放得到恢复 [(12 8.30± 8.2 9)∶(12 6 .4 0± 8.0 9) pmol/L ,P >0 .0 5 ],而浕2 肾上腺素能受体阻滞剂育亨宾则对其无明显影响 [(5 4 .70± 10 .2 7)∶(12 7.5 0± 7.87)pmol/L ,P <0 .0 1];③腺苷受体激动剂 2 苯异丙基腺苷使非缺血大鼠心脏交感神经末梢NA的释放受到明显抑制 (6 1.70± 10 .6 5∶12 6 .30±14 .18,P <0 .0 1) ,而α2 肾上腺素能激动剂可乐定则对其无明显影响 [(130 .0 0± 9.90 )∶(130 .4± 10 .33)pmol/L ,P >0 .0 5 ]。结论 :心脏较长时间的缺血可引起交感神经顿抑 ,且内源性腺苷起重要作用。

Objective:The aim of this study was to support the concept of the postischemic neuronal dysfunction(neuronal stunning) and to assess the role of presynaptic adenosine receptors and α 2 adrenoceptors in neuronal stunning.Methods:Exocytotic noradrenaline(NA) release was induced by two electrical field stimulations(S 1 & S 2) in isolated perfused rat hearts. S1 was performed under baseline conditions and S2 either during or following intervension.Results:①Global ischemia for 30 min induced a suppression of NA release in the posteschemic heart, which was reversible during reperfusion though difficult(S 2/S 1: 0.23 ± 0.031 , 0.41 ± 0.043 & 0.62 ± 0.053 , respectively; all P< 0.01 );②The adenosine receptor antagonist 8 phenyltheophylline significantly increased NA release after 30-min ischemia and 5 min reperfusion [( 128.30 ± 8.29 ) vs ( 126.40 ± 8.09 ) pmol/L, P> 0.05 ], while in the same experimental protocol blockade of α 2 adrenoceptor by yohimbine failed to restore the postischemic release [( 54.70 ± 10.27 ) vs ( 127.50 ± 7.87 ) pmol/L, P< 0.01 ]; ③ In non ischemic hearts the adenosine analogue 2 phenylisopropyl adenosine resulted in a marked suppression of NA release [( 61.70 ± 10.65 ) vs ( 126.30 ± 14.18 ) pmol/L, P< 0.01 ], while activation of α 2 adrenoceptor by clonidine did not cause a reduction of NA release( 130.00 ± 9.90 ) vs ( 130.40 ± 10.33 ) pmol/L, P> 0.05 ]..Conclusion:The phenomenon of neuronal stunning in terms of a postischemic suppression of exocytotic NA release is established and may be mediated by endogenous adenosine.