Wortmann A, Bachmann K, Meinhold M
Medizinische Klinik II, Kardiologie, Medizinische Poliklinik, Erlangen, F.R.G.
Eur Heart J. 1988 Jan;9 Suppl A:119-24. doi: 10.1093/eurheartj/9.suppl_a.119.
One of the most promising concepts in nitrate therapy is interval therapy, a dosage scheme with marked changes of nitrate concentrations in the 24-h interval. In a single-blind, placebo-controlled study in patients with coronary heart disease we investigated the circadian anti-ischaemia and haemodynamic response to interval therapy with isosorbide dinitrate (120 mg sustained release 1 X 1). 10 male patients (46-75 years, mean 60 years) with chronic stable angina and ST-segment depression during exercise entered the trial. At the end of a 10-day placebo period (medication at 8 am) three exercise tests were performed (10 am, 2 pm, 6 pm), recording ST-segment changes, pulmonary capillary wedge pressure (PCP) and cardiac index (CI). Spontaneous ischaemic events were detected by Holter monitoring until 8 am the next day. After three weeks of therapy with isosorbide dinitrate, the protocol was repeated (statistics: paired t-test, P less than 0.05). PCP was reduced by 8.3 mmHg at 10 am, 8.0 mmHg at 2 pm, 2.9 mmHg (NS) at 6 pm with a concomitant increase of cardiac index (+0.8,* +0.7*, +0.3 NS l min-1 m-2). While the haemodynamic improvement was maximal in the morning the anti-ischaemia effect (reduction of ST-depression) was constant during the active day (-0.40*, -0.50*, -0.43* mm). Four transient ischaemia episdodes at night were recorded under placebo, none under isosorbide dinitrate. In conclusion, all parameters studied demonstrate the effectiveness of chronic interval therapy with isosorbide dinitrate.
硝酸盐疗法中最有前景的概念之一是间歇疗法，这是一种在24小时内硝酸盐浓度有显著变化的给药方案。在一项针对冠心病患者的单盲、安慰剂对照研究中，我们调查了二硝酸异山梨酯（120毫克缓释制剂，每日1次）间歇疗法的昼夜抗缺血和血流动力学反应。10名患有慢性稳定型心绞痛且运动时ST段压低的男性患者（46 - 75岁，平均60岁）进入试验。在为期10天的安慰剂期（上午8点服药）结束时，进行了三次运动试验（上午10点、下午2点、下午6点），记录ST段变化、肺毛细血管楔压（PCWP）和心脏指数（CI）。通过动态心电图监测直至次日上午8点，检测自发性缺血事件。在用二硝酸异山梨酯治疗三周后，重复该方案（统计学方法：配对t检验，P < 0.05）。上午10点时PCWP降低8.3 mmHg，下午2点时降低8.0 mmHg，下午6点时降低2.9 mmHg（无统计学意义），同时心脏指数增加（分别为+0.8*、+0.7*、+0.3，无统计学意义，升/分钟·平方米）。虽然血流动力学改善在早晨最大，但抗缺血作用（ST段压低的降低）在活动日期间是恒定的（分别为-0.40*、-0.50*、-0.43*毫米）。安慰剂组记录到夜间有4次短暂缺血发作，二硝酸异山梨酯组未记录到。总之，所有研究参数均表明二硝酸异山梨酯慢性间歇疗法是有效的。
