Dart A M, Riemersma R A, Schömig A, Ungar A
Br J Pharmacol. 1987 Jan;90(1):43-50. doi: 10.1111/j.1476-5381.1987.tb16823.x.
The metabolic conditions required for noradrenaline (NA) release from ischaemic and anoxic perfused hearts of the rat were studied. Forty minutes of flow reduction to approximately 0.25 ml g-1 min-1 did not elicit enhanced noradrenaline overflow from the isolated heart perfused with normoxic perfusate even in the absence of added substrate. Enhanced overflow did occur when substrate-free ischaemia was induced after a 60 min period of substrate-free perfusion. Noradrenaline overflow was enhanced by perfusion at normal flow rates with an anoxic (Po2 less than or equal to 1 mmHg) perfusate containing no substrate. Such enhanced overflow occurred in the absence of calcium in the perfusate and was almost completely abolished by the addition of 11 mM glucose. Enhanced noradrenaline overflow occurring either during low flow ischaemia after substrate deprivation or during anoxic substrate-free perfusion at normal flow rates was markedly suppressed by desipramine. Exocytotic noradrenaline overflow induced by electrical stimulation of the left cervico-thoracic ganglion continued unchanged during 60 min of anoxia if the perfusate contained 11 mM glucose. In the absence of added substrate there was a decline in the overflow induced by such stimulation which was more rapid with anoxic than normoxic perfusate. Re-introduction of calcium, oxygen and substrate after 10, 20 or 30 min of calcium-free, substrate-free, anoxic perfusion was associated with a massive overflow of the intracellular enzyme lactate dehydrogenase. At 10 min there was an associated transient minor increase in NA overflow but at 20 and 30 min the overflow of NA, elevated as a result of anoxic perfusion, returned to pre-anoxic levels on the re-introduction of substrate and oxygen. 7 These studies demonstrate a central role for the metabolic status of the sympathetic nerve terminal in determining the magnitude ofexocytotic and nerve-impulse independent noradrenaline release from the heart. During the course of myocardial ischaemia in vivo nerve-impulse independent release would be expected to occur only in regions of severe flow reduction. This may produce heterogeneous stimulation of the myocardium.
研究了大鼠缺血和缺氧灌注心脏释放去甲肾上腺素（NA）所需的代谢条件。即使在不添加底物的情况下，将流量降低至约0.25 ml g-1 min-1持续40分钟，也不会引起用常氧灌注液灌注的离体心脏中去甲肾上腺素溢出增加。在无底物灌注60分钟后诱导无底物缺血时，确实发生了溢出增加。用不含底物的缺氧（Po2小于或等于1 mmHg）灌注液以正常流速灌注可增强去甲肾上腺素溢出。这种增强的溢出发生在灌注液中无钙的情况下，加入11 mM葡萄糖后几乎完全消除。地昔帕明可显著抑制在底物剥夺后的低流量缺血期间或正常流速下的缺氧无底物灌注期间发生的去甲肾上腺素溢出增强。如果灌注液含有11 mM葡萄糖，在缺氧60分钟期间，通过电刺激左颈胸神经节诱导的胞吐性去甲肾上腺素溢出保持不变。在不添加底物的情况下，这种刺激诱导的溢出会下降，缺氧灌注液比常氧灌注液下降得更快。在无钙、无底物、缺氧灌注10、20或30分钟后重新引入钙、氧和底物，与细胞内酶乳酸脱氢酶的大量溢出有关。在10分钟时，NA溢出有相关的短暂轻微增加，但在20和30分钟时，由于缺氧灌注而升高的NA溢出在重新引入底物和氧后恢复到缺氧前水平。这些研究表明，交感神经末梢的代谢状态在决定心脏中胞吐性和神经冲动非依赖性去甲肾上腺素释放的程度方面起着核心作用。在体内心肌缺血过程中，预计仅在严重血流减少的区域会发生神经冲动非依赖性释放。这可能会对心肌产生异质性刺激。
