Gao F, Christopher T A, Lopez B L, Friedman E, Cai G, Ma X L
Department of Surgery, Thomas Jefferson University, Philadelphia 19107, Pennsylvania, USA.
Am J Physiol Heart Circ Physiol. 2000 Jul;279(1):H329-38. doi: 10.1152/ajpheart.2000.279.1.H329.
The purpose of this study was to determine whether the protective effects of adenosine on myocardial ischemia-reperfusion injury are altered with age, and if so, to clarify the mechanisms that underlie this change related to nitric oxide (NO) derived from the vascular endothelium. Isolated perfused rat hearts were exposed to 30 min of ischemia and 60 min of reperfusion. In the adult hearts, administration of adenosine (5 micromol/l) stimulated NO release (1. 06 +/- 0.19 nmol. min(-1). g(-1), P < 0.01 vs. vehicle), increased coronary flow, improved cardiac functional recovery (left ventricular developed pressure 79 +/- 3.8 vs. 57 +/- 3.1 mmHg in vehicle, P < 0.001; maximal rate of left ventricular pressure development 2,385 +/- 103 vs. 1,780 +/- 96 in vehicle, P < 0.001), and reduced myocardial creatine kinase loss (95 +/- 3.9 vs. 159 +/- 4.6 U/100 mg protein, P < 0.01). In aged hearts, adenosine-stimulated NO release was markedly reduced (+0.42 +/- 0.12 nmol. min(-1). g(-1) vs. vehicle), and the cardioprotective effects of adenosine were also attenuated. Inhibition of NO production in the adult hearts significantly decreased the cardioprotective effects of adenosine, whereas supplementation of NO in the aged hearts significantly enhanced the cardioprotective effects of adenosine. The results show that the protective effects of adenosine on myocardial ischemia-reperfusion injury are markedly diminished in aged animals, and that the loss in NO release in response to adenosine may be at least partially responsible for this age-related alteration.
本研究旨在确定腺苷对心肌缺血-再灌注损伤的保护作用是否随年龄而改变，若有改变，则阐明与血管内皮衍生的一氧化氮（NO）相关的这种变化的潜在机制。将离体灌注的大鼠心脏暴露于30分钟的缺血和60分钟的再灌注。在成年心脏中，给予腺苷（5微摩尔/升）刺激NO释放（1.06±0.19纳摩尔·分钟-1·克-1，与溶剂相比P<0.01），增加冠脉流量，改善心脏功能恢复（左心室舒张末压在溶剂组为79±3.8，腺苷组为57±3.1毫米汞柱，P<0.001；左心室压力最大上升速率在溶剂组为2385±103，腺苷组为1780±96，P<0.001），并减少心肌肌酸激酶损失（95±3.9与159±4.6单位/100毫克蛋白质，P<0.01）。在老年心脏中，腺苷刺激的NO释放明显减少（与溶剂相比为+0.42±0.12纳摩尔·分钟-1·克-1），腺苷的心脏保护作用也减弱。抑制成年心脏中的NO生成显著降低了腺苷的心脏保护作用，而在老年心脏中补充NO则显著增强了腺苷的心脏保护作用。结果表明，腺苷对心肌缺血-再灌注损伤的保护作用在老年动物中明显减弱，并且腺苷诱导的NO释放减少可能至少部分导致了这种与年龄相关的改变。
