Parker J D, Testa M A, Jimenez A H, Tofler G H, Muller J E, Parker J O, Stone P H
Cardiovascular Division, Brigham and Women's Hospital, Boston.
Circulation. 1994 Feb;89(2):604-14. doi: 10.1161/01.cir.89.2.604.
The morning increase in asymptomatic ambulatory ischemia may be due to heightened coronary tone, increased physical activity, or both. If ambulatory ischemia is primarily due to physical activity, then alterations in the schedule of physical activity should be reflected in a corresponding alteration in the occurrence of ischemia. This study was designed to examine the relation between activity patterns and the frequency of ambulatory ischemic episodes and the effect of nadolol on these relations.
A double-blind, randomized, placebo-controlled, crossover trial of nadolol versus placebo was performed in 20 patients with stable coronary artery disease. At the end of each 2-week treatment phase, patients were hospitalized for 48 hours. In the hospital, there was a regular activity day (awaken and assume normal activities at 8:00 AM) and a delayed activity day (awaken at 8:00 AM, arise at 10:00 AM, and begin normal activity at noon). Ambulatory ECG monitoring was performed throughout the hospitalization. On the regular activity day, there was a morning increase in heart rate and in the number of ischemic episodes during therapy with placebo that began at 8:00 AM. In contrast, on the delayed activity day, there was a 4-hour phase shift of the increases in heart rate and the increase in ischemic episodes (ie, at noon) corresponding to the onset of physical activities. Therapy with nadolol caused a 50% reduction in the total number of ischemic episodes (129 versus 65, placebo versus nadolol; P < .02). During nadolol therapy, there was no discernible circadian peak in the number of ischemic episodes on either activity day. During placebo treatment, 87% of ischemic episodes were preceded by an increase in heart rate > or = 5 beats per minute. Although nadolol caused a significant reduction in the total number of episodes preceded by a heart rate increase compared with placebo (99 versus 38 episodes, P < .04), this therapy was associated with a significant increase in the number of episodes not associated with a heart rate increase (15 versus 21 episodes, P < .002).
The morning increase in ambulatory ischemic episodes is due to physical activity patterns. The majority of ischemic episodes are preceded by a heart rate increase, and it is these episodes that are primarily responsible for the morning increase in ischemia. Therapy with nadolol caused a reduction in the total number of ischemic episodes solely by reducing those episodes preceded by a heart rate increase. In contrast, nadolol caused a significant increase in the number of ischemic episodes not associated with a heart rate increase, perhaps in part because it potentiated coronary vasoconstriction.
无症状动态性心肌缺血在早晨的增加可能是由于冠状动脉张力升高、体力活动增加或两者兼而有之。如果动态性心肌缺血主要是由于体力活动引起的，那么体力活动时间表的改变应该会反映在缺血发生情况的相应改变上。本研究旨在探讨活动模式与动态性缺血发作频率之间的关系以及纳多洛尔对这些关系的影响。
对20例稳定型冠状动脉疾病患者进行了纳多洛尔与安慰剂的双盲、随机、安慰剂对照、交叉试验。在每个为期2周的治疗阶段结束时，患者住院48小时。在医院里，有一个常规活动日（上午8:00醒来并进行正常活动）和一个延迟活动日（上午8:00醒来，上午10:00起床，中午开始正常活动）。在整个住院期间进行动态心电图监测。在常规活动日，服用安慰剂治疗时，上午8:00开始心率和缺血发作次数会增加。相比之下，在延迟活动日，心率增加和缺血发作增加（即中午）出现了4小时的相位偏移，与体力活动开始时间相对应。纳多洛尔治疗使缺血发作总数减少了50%（安慰剂组129次，纳多洛尔组65次；P<.02）。在纳多洛尔治疗期间，在任何一个活动日缺血发作次数均无明显的昼夜高峰。在安慰剂治疗期间，87%的缺血发作之前心率增加≥5次/分钟。尽管与安慰剂相比，纳多洛尔使心率增加之前的发作总数显著减少（99次对38次，P<.04），但这种治疗与心率未增加的发作次数显著增加有关（15次对21次，P<.002）。
动态性缺血发作在早晨的增加是由于体力活动模式。大多数缺血发作之前心率会增加，正是这些发作主要导致了早晨缺血的增加。纳多洛尔治疗仅通过减少心率增加之前的发作次数使缺血发作总数减少。相比之下，纳多洛尔使与心率增加无关的缺血发作次数显著增加，这可能部分是因为它增强了冠状动脉血管收缩。
