Wanna F S, Obayashi D Y, Young J N, DeCampli W M
Children's Hospital Oakland Research Institute, Calif., USA.
J Thorac Cardiovasc Surg. 1995 Oct;110(4 Pt 1):1054-62. doi: 10.1016/s0022-5223(05)80174-6.
The effects of aspirin and L-arginine (biological precursor of nitric oxide) on the production of hydroxyl radicals, cyclic guanosine monophosphate levels, vascular tone, and the recovery of the ischemic myocardium were investigated in isolated rat hearts subjected to ischemia and reperfusion. After 30 minutes of perfusion, hearts were arrested with St. Thomas' Hospital cardioplegic solution, global ischemia was induced at 37 degrees C for 45 minutes, and the hearts were then reperfused at 37 degrees C for 30 minutes. The percent change in recovery of pulse pressure and maximal change of this pressure with time were better in the group perfused with Krebs-Henseleit solution containing aspirin plus L-arginine (17% +/- 23%, p = 0.001, and 10% +/- 25%, p = 0.002, respectively) compared with these values in the control group perfused with Krebs-Henseleit solution alone (-7% +/- 14% and -11% +/- 16%, respectively). Coronary vascular resistance before and after ischemia were lower in the aspirin plus L-arginine group (0.19 +/- 0.03 dynes.sec/cm5, p = 0.001, and 0.23 +/- 0.04 dynes.sec/cm5, p = 0.01, respectively) compared with those of the control group (0.24 +/- 0.02 and 0.28 +/- 0.07 dynes.sec/cm5, respectively). Cyclic guanosine monophosphate levels increased from 22.5 +/- 6 pmol/100 mg of tissue in the control group to 37.1 +/- 8.9 pmol/100 mg (p = 0.002) in the aspirin plus L-arginine group. Adding N omega-nitro-L-arginine methyl ester to the perfusion medium caused a deterioration in pulse pressure and maximal change of this pressure with time, a decrease in cyclic guanosine monophosphate, and a rise in coronary vascular resistance. The addition of L-arginine to the solution in the Krebs-Henseleit solution plus aspirin group increased the production of hydroxyl radicals from 0.32 +/- 0.18 nmol/gm per 3 minutes to 0.75 +/- 0.33 nmol/gm per 3 minutes (p = 0.03). Despite the association of nitric oxide with increased hydroxyl radical production, it appears that nitric oxide has an overall beneficial effect on the recovery of the ischemic myocardium. The synergism between aspirin and arginine may be caused in part by the scavenging of hydroxyl radicals. Alternatively, by inhibiting the prostaglandin pathway, aspirin may reduce the generation of superoxide anion, a free radical that inactivates nitric oxide. The prolonged half-life of nitric oxide may explain the increased levels of cyclic guanosine monophosphate seen in the group perfused with Krebs-Henseleit solution plus aspirin plus L-arginine. Aspirin and L-arginine, both readily available, may be useful adjuncts to clinical cardioplegia strategy.
在经历缺血再灌注的离体大鼠心脏中，研究了阿司匹林和L-精氨酸（一氧化氮的生物前体）对羟自由基生成、环磷酸鸟苷水平、血管张力以及缺血心肌恢复的影响。灌注30分钟后，用圣托马斯医院心脏停搏液使心脏停搏，在37℃诱导全心缺血45分钟，然后在37℃再灌注30分钟。与单独用克雷布斯-亨泽莱特溶液灌注的对照组相比，用含阿司匹林加L-精氨酸的克雷布斯-亨泽莱特溶液灌注的组中，脉压恢复的百分比变化以及该压力随时间的最大变化更好（分别为17%±23%，p = 0.001，和10%±25%，p = 0.002），而对照组的这些值分别为-7%±14%和-11%±16%。缺血前后阿司匹林加L-精氨酸组的冠状动脉血管阻力低于对照组（分别为0.19±0.03达因·秒/厘米⁵，p = 0.001，和0.23±0.04达因·秒/厘米⁵，p = 0.01），对照组分别为0.24±0.02和0.28±0.07达因·秒/厘米⁵。环磷酸鸟苷水平从对照组的22.5±6皮摩尔/100毫克组织增加到阿司匹林加L-精氨酸组的37.1±8.9皮摩尔/100毫克（p = 0.002）。向灌注液中添加Nω-硝基-L-精氨酸甲酯会导致脉压及其随时间的最大变化恶化、环磷酸鸟苷减少以及冠状动脉血管阻力升高。在克雷布斯-亨泽莱特溶液加阿司匹林组的溶液中添加L-精氨酸，使羟自由基生成从每3分钟0.32±0.18纳摩尔/克增加到每3分钟0.75±0.33纳摩尔/克（p = 0.03）。尽管一氧化氮与羟自由基生成增加有关，但一氧化氮似乎对缺血心肌的恢复具有总体有益作用。阿司匹林和精氨酸之间的协同作用可能部分是由于羟自由基的清除。或者，通过抑制前列腺素途径，阿司匹林可能减少超氧阴离子的生成，超氧阴离子是一种使一氧化氮失活的自由基。一氧化氮延长的半衰期可能解释了在灌注克雷布斯-亨泽莱特溶液加阿司匹林加L-精氨酸组中看到的环磷酸鸟苷水平升高。阿司匹林和L-精氨酸都易于获得，可能是临床心脏停搏策略的有用辅助药物。
