Leung Felix W, Chan Chi Chung
Research and Medical Services, Sepulveda Ambulatory Care Center, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, Los Angeles, California 91343, USA.
Dig Dis Sci. 2007 Sep;52(9):2229-35. doi: 10.1007/s10620-006-9266-2. Epub 2007 Apr 10.
Clinical studies reveal that aspirin intake to prevent myocardial and cerebral ischemia is associated with a significant increase in upper gastrointestinal hemorrhage requiring hospitalization and that nitroglycerin or long-acting nitrates significantly lower this risk. Nitroglycerin can increase gastric blood flow and slow gastric emptying. We hypothesized that both features contribute to its gastroprotective property. Fasted anesthetized rats (Study 1) and conscious mice (Studies 2 to 4) received intragastric nitroglycerin or vehicle. The effects of these two treatments on various parameters were assessed in Study 1, on blood pressure and gastric blood flow; Study 2, on acidified aspirin-induced gastric mucosal lesions; and Study 3, on the weight of gastric content. In Study 4, the effect of nitroglycerin, vehicle, or vehicle plus saline, on acidified aspirin-induced gastric mucosal lesion was assessed. Compared with vehicle, nitroglycerin decreased blood pressure and produced a mild but significant increase in gastric vascular conductance, blood flow, and volume of gastric content. The number and length of gastric mucosal lesions induced by acidified aspirin were significantly attenuated by intragastric nitroglycerin in a vasodilatory dose. Exogenous saline in a volume equivalent to the increase produced by nitroglycerin, however, did not attenuate the lesions. These experimental data are consistent with the clinical observation that nitrates lower the risk of aspirin-induced gastrointestinal complications. Confirmation of the efficacy of nitroglycerin and nitrates in preventing such aspirin-induced complications in controlled trials is worthy of consideration by clinical investigators.
临床研究表明，服用阿司匹林预防心肌和脑缺血与需要住院治疗的上消化道出血显著增加有关，而硝酸甘油或长效硝酸盐可显著降低这种风险。硝酸甘油可增加胃血流量并减缓胃排空。我们推测这两个特性都有助于其胃保护作用。禁食麻醉大鼠（研究1）和清醒小鼠（研究2至4）接受胃内给予硝酸甘油或赋形剂。在研究1中评估了这两种处理对各种参数的影响，包括血压和胃血流量；在研究2中评估了对酸化阿司匹林诱导的胃黏膜损伤的影响；在研究3中评估了对胃内容物重量的影响。在研究4中，评估了硝酸甘油、赋形剂或赋形剂加生理盐水对酸化阿司匹林诱导的胃黏膜损伤的影响。与赋形剂相比，硝酸甘油降低了血压，并使胃血管传导性、血流量和胃内容物体积有轻度但显著的增加。胃内给予血管舒张剂量的硝酸甘油可显著减轻酸化阿司匹林诱导的胃黏膜损伤的数量和长度。然而，与硝酸甘油增加的量相当的外源性生理盐水并没有减轻损伤。这些实验数据与临床观察结果一致，即硝酸盐可降低阿司匹林诱导的胃肠道并发症的风险。临床研究人员值得考虑在对照试验中证实硝酸甘油和硝酸盐预防此类阿司匹林诱导并发症的疗效。
