Benhorin J, Banai S, Moriel M, Gavish A, Keren A, Stern S, Tzivoni D
Heiden Department of Cardiology, Bikur Cholim Hospital, Jerusalem, Israel.
Circulation. 1993 Mar;87(3):808-14. doi: 10.1161/01.cir.87.3.808.
The occurrence of ischemic episodes during daily activity has been reported to exhibit a bimodal circadian distribution, yet its relation to the ischemic threshold (heart rate at 1-mm ST segment depression) has not been explored.
To determine whether the ischemic threshold during daily activity exhibits a circadian pattern that might relate to the frequency of occurrence of ischemic episodes, we studied the time of occurrence and the heart rate at onset of ischemia in 1,371 ischemic episodes recorded in 41 patients with stable coronary disease, positive exercise testing, and repeated ischemic episodes during ambulatory ECG monitoring (AEM). All patients had 7 days of AEM; 23 were off any anti-ischemic therapy, while 18 were on low dose of beta-blockers. The occurrence of ischemic episodes exhibited the typical bimodal circadian distribution with a prominent peak between 7:00 and 11:00 AM and a second less prominent peak between 6:00 and 9:00 PM. The threshold of myocardial ischemia exhibited a different single-peaked circadian distribution; it was lowest between 1:00 and 3:00 AM and highest between 10 AM and 1 PM. Time series analyses indicated a strong hour-by-hour trend of each of the two circadian distributions, whereas the two series cross-correlated maximally at a lag of zero hours (p < 0.01), indicating a complex interplay between myocardial oxygen demand and supply in determining the occurrence of ischemic episodes during daily activity. The morning increase in the frequency of ischemic episodes could not be attributed to a reduced threshold but rather to an increase in demand. The low threshold at night-time might probably indicate that the mechanism of ischemia during these hours is reduced coronary flow due to increased coronary tone. Secondary analyses for several predefined patients' subsets gave similar results. Patients who received low-dose beta-blockers maintained the bimodal circadian distribution of the occurrence of ischemic episodes, whereas the ischemic threshold exhibited a constant pattern with no circadian changes.
Our results demonstrate that myocardial oxygen demand is a major determinant of daily ischemia, yet changes in the ischemic threshold that probably reflect dynamic changes in coronary tone play also an important role. The relative contribution of increased demand and decreased threshold to the genesis of ischemic episodes during daily activity can be assessed by AEM and may help to optimize medical therapy.
据报道，日常活动期间缺血发作的发生呈现双峰昼夜分布，但其与缺血阈值（ST段压低1毫米时的心率）的关系尚未得到探讨。
为了确定日常活动期间的缺血阈值是否呈现与缺血发作频率相关的昼夜模式，我们研究了41例冠心病稳定、运动试验阳性且动态心电图监测（AEM）期间反复出现缺血发作的患者记录的1371次缺血发作的发生时间和缺血发作开始时的心率。所有患者均进行了7天的AEM监测；23例未接受任何抗缺血治疗，18例接受低剂量β受体阻滞剂治疗。缺血发作的发生呈现典型的双峰昼夜分布，上午7:00至11:00之间有一个明显的峰值，下午6:00至9:00之间有第二个不太明显的峰值。心肌缺血阈值呈现不同的单峰昼夜分布；凌晨1:00至3:00之间最低，上午10:00至下午1:00之间最高。时间序列分析表明，这两种昼夜分布中的每一种都有很强的逐小时趋势，而这两个序列在零时滞时交叉相关性最大（p < 0.01），表明在日常活动中确定缺血发作的发生时，心肌氧需求和供应之间存在复杂的相互作用。上午缺血发作频率的增加不能归因于阈值降低，而应归因于需求增加。夜间较低的阈值可能表明这些时间段内缺血的机制是由于冠状动脉张力增加导致冠状动脉血流减少。对几个预先定义的患者亚组的二次分析得出了类似的结果。接受低剂量β受体阻滞剂治疗的患者缺血发作的发生保持双峰昼夜分布，而缺血阈值呈现恒定模式，无昼夜变化。
我们的结果表明，心肌氧需求是日常缺血的主要决定因素，但缺血阈值的变化可能反映冠状动脉张力的动态变化，也起着重要作用。通过AEM可以评估日常活动期间需求增加和阈值降低对缺血发作发生的相对贡献，这可能有助于优化药物治疗。
