Minamino T, Kitakaze M, Sanada S, Asanuama H, Kurotobi T, Koretsune Y, Fukunami M, Kuzuya T, Hoki N, Hori M
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Circulation. 1998 Oct 27;98(17):1721-7. doi: 10.1161/01.cir.98.17.1721.
Platelet activation and decreased levels of nitrite and nitrate (NOx), stable end products of nitric oxide (NO), are reported in patients with atrial fibrillation (AF). We examined the time-course changes in plasma NOx levels and the expression of P-selectin on platelets after the onset of AF in a canine model and determined whether these parameters could be risk factors for silent cerebral infarction in patients with AF.
AF was induced by rapid atrial pacing in the canine model of AF. Plasma NOx levels were significantly decreased and the levels of P-selectin on platelets and of neutrophil/platelet conjugates were significantly increased after the onset of AF in this model. The in vitro experiments demonstrated that the inhibition of NO synthesis increased the expression of P-selectin on platelets. Plasma NOx levels (19.7+/-2.4 versus 27.5+/-2.8 micromol/L) were significantly lower in 25 patients with AF compared with age- (+/-2 years) and sex-matched control subjects. Conversely, the levels of P-selectin on platelets (7.6+/-0.8% versus 4.8+/-0.7%) and of neutrophil/platelet conjugates (14.8+/-0.9% versus 8.1+/-0.6%) were significantly higher in patients with AF. Multiple regression analysis revealed that increased P-selectin on platelets and advanced age were associated with the number of foci of silent cerebral infarction.
An irregular heart rate that is characteristic of AF appeared to blunt NO synthesis. The increased expression of P-selectin on platelets associated with the reduced NO levels was a risk factor for silent cerebral infarction in patients with AF.
心房颤动（AF）患者存在血小板活化以及亚硝酸盐和硝酸盐（NOx）水平降低的情况，NOx是一氧化氮（NO）的稳定终产物。我们在犬类模型中研究了房颤发作后血浆NOx水平的时间进程变化以及血小板上P-选择素的表达，并确定这些参数是否可能是房颤患者无症状性脑梗死的危险因素。
在犬类房颤模型中通过快速心房起搏诱发房颤。在此模型中，房颤发作后血浆NOx水平显著降低，血小板上P-选择素水平以及中性粒细胞/血小板结合物水平显著升高。体外实验表明，抑制NO合成可增加血小板上P-选择素的表达。与年龄（±2岁）和性别匹配的对照受试者相比，25例房颤患者的血浆NOx水平（19.7±2.4对27.5±2.8 μmol/L）显著较低。相反，房颤患者血小板上P-选择素水平（7.6±0.8%对4.8±0.7%）以及中性粒细胞/血小板结合物水平（14.8±0.9%对8.1±0.6%）显著较高。多元回归分析显示，血小板上P-选择素增加和高龄与无症状性脑梗死灶数量相关。
房颤特有的心率不齐似乎会抑制NO合成。与NO水平降低相关的血小板上P-选择素表达增加是房颤患者无症状性脑梗死的危险因素。
