Toyosaki N, Katsuki T, Fujii M, Kawada Y, Komaba A, Watabiki H, Hasegawa H, Suzuki S, Natsume T, Yaginuma T
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Jpn Circ J. 1989 May;53(5):395-405. doi: 10.1253/jcj.53.395.
The development and reversal of tolerance to the hemodynamic and anti-anginal effects of isosorbide dinitrate in a sustained release form (ISDN-SR) were investigated in 11 male patients (mean age 58.9 y.o.) with stable effort angina. Treadmill exercise test, evaluation of hemodynamic parameters and measurement of plasma ISDN concentrations were performed during the control period, on the 1st, 7th and 14th days of therapy with 40 mg of ISDN-SR orally every 8 h and, subsequently, on the day when ISDN-SR was re-administered after a 72 h placebo period (17th day). Initially, exercise tolerance time (ETT) was prolonged significantly (p less than 0.001) by ISDN-SR from 257 +/- 50 sec in the control period to 434 +/- 55 sec on day 1. This prolongation was significantly reduced with sustained therapy and ETT was shortened to 332 +/- 69 sec on the 7th day (p less than 0.01 vs day 1) and 326 +/- 73 sec on the 14th day (p less than 0.01 vs day 1). The effects of ISDN-SR initially observed were restored after a 72 h placebo period and ETT was prolonged to 432 +/- 57 sec on the 17th day. The resting heart rate was increased significantly (p less than 0.01 vs control) and systolic blood pressure was decreased (p less than 0.001 vs control) by ISDN-SR on day 1. These changes were also diminished significantly (p less than 0.01 vs day 1) with sustained therapy and were restored after a 72 h nitrate-free interval.(ABSTRACT TRUNCATED AT 250 WORDS)
在11名患有稳定劳力性心绞痛的男性患者（平均年龄58.9岁）中，研究了对缓释型硝酸异山梨酯（ISDN-SR）血流动力学和抗心绞痛作用耐受性的发展及逆转情况。在对照期、每8小时口服40毫克ISDN-SR治疗的第1天、第7天和第14天，以及随后在72小时安慰剂期后重新给予ISDN-SR的当天（第17天），进行了平板运动试验、血流动力学参数评估和血浆ISDN浓度测量。最初，ISDN-SR使运动耐受时间（ETT）显著延长（p<0.001），从对照期的257±50秒延长至第1天的434±55秒。持续治疗后这种延长显著减少，ETT在第7天缩短至332±69秒（与第1天相比p<0.01），在第14天缩短至326±73秒（与第1天相比p<0.01）。72小时安慰剂期后，最初观察到的ISDN-SR的作用得以恢复，第17天ETT延长至432±57秒。第1天，ISDN-SR使静息心率显著增加（与对照相比p<0.01），收缩压降低（与对照相比p<0.001）。持续治疗后这些变化也显著减弱（与第1天相比p<0.01），并在72小时无硝酸盐间隔后恢复。（摘要截短于250字）
