Du X J, Riemersma R A
Department of Medicine (RIE), University of Edinburgh, United Kingdom.
Basic Res Cardiol. 1991 Jan-Feb;86(1):11-20. doi: 10.1007/BF02193867.
The effects of severity and duration of acute myocardial ischaemia on left stellate ganglion stimulation-induced noradrenaline (NA) overflow were studied in the retrogradely perfused, innervated rat heart. A 10-min period of ischaemia induced by a coronary flow reduction of 100% (0 ml/g/min), 95% (0.24 ml/g/min) and 90% (0.48 ml/g/min) reduced neuronal NA overflow to 24 +/- 4% (p less than 0.01), 62 +/- 6% (p less than 0.05) and 70 +/- 6% (p less than 0.05) of the normoxic control values, respectively. During low-flow ischaemia, a progressive decline in neuronal NA overflow was found in hearts subjected to 95% flow reduction, but not to 90% flow reduction. The effect of ischaemia on presynaptic control of NA release was also examined. After 10 min of stop-flow ischaemia, the alpha-adrenergic antagonist phentolamine (1 microM) and the adenosine receptor antagonist 8-phenyltheophylline (10 microM) failed to restore neuronal NA overflow to pre-ischaemic levels (from 24 +/- 4% without drug to 23 +/- 4% or 41 +/- 10%, respectively, NS). In contrast, after 60 min of low-flow ischaemia (95% flow reduction), phentolamine and 8-phenyltheophylline largely restored neuronal NA overflow to normoxic control values (from 32 +/- 3% without drug to 61 +/- 11% (p less than 0.05) or 79 +/- 11% (p less than 0.01), respectively). During prolonged low-flow ischaemia (95%), the neuronal NA reuptake inhibitor desipramine (0.1 microM) doubled NA overflow induced by nerve stimulation, suggesting an effective neuronal reuptake during these conditions. In conclusion, the severity of ischaemia critically affects neuronal NA release and its controlling mechanisms. Thus, heterogeneity of myocardial ischaemia may lead to gradients in NA release and myocardial adrenergic stimulation.
在逆行灌注、有神经支配的大鼠心脏中，研究了急性心肌缺血的严重程度和持续时间对左星状神经节刺激诱导的去甲肾上腺素（NA）溢出的影响。通过将冠状动脉血流量分别减少100%（0毫升/克/分钟）、95%（0.24毫升/克/分钟）和90%（0.48毫升/克/分钟）诱导10分钟的缺血，使神经元NA溢出分别降至正常氧合对照值的24±4%（p<0.01）、62±6%（p<0.05）和70±6%（p<0.05）。在低流量缺血期间，在血流量减少95%的心脏中发现神经元NA溢出逐渐下降，但在血流量减少90%的心脏中未发现。还研究了缺血对NA释放的突触前控制的影响。在停止血流缺血10分钟后，α-肾上腺素能拮抗剂酚妥拉明（1微摩尔）和腺苷受体拮抗剂8-苯基茶碱（10微摩尔）未能将神经元NA溢出恢复到缺血前水平（分别从无药物时的24±4%降至23±4%或41±10%，无统计学意义）。相反，在低流量缺血60分钟（血流量减少95%）后，酚妥拉明和8-苯基茶碱将神经元NA溢出大部分恢复到正常氧合对照值（分别从无药物时的32±3%升至61±11%（p<0.05）或79±11%（p<0.01））。在长时间低流量缺血（95%）期间，神经元NA再摄取抑制剂地昔帕明（0.1微摩尔）使神经刺激诱导的NA溢出增加一倍，表明在这些情况下存在有效的神经元再摄取。总之，缺血的严重程度严重影响神经元NA释放及其控制机制。因此，心肌缺血的异质性可能导致NA释放和心肌肾上腺素能刺激的梯度变化。
