Relations between heart rate, ischemia, and drug therapy during daily life in patients with coronary artery disease

BACKGROUND. Previous studies have shown that little if any increase in heart rate occurs 1 minute before the onset of ischemia in ambulant patients with coronary artery disease. This study tested the hypothesis that there are characteristic relations between heart rate and ischemia in ambulant patients with coronary artery disease. METHODS AND RESULTS. Twenty-one patients with proven coronary disease demonstrated 212 episodes of ischemia during 504 hours of continuous monitoring of the electrocardiogram. An important increase in heart rate (from 74 +/- 11 to 90 +/- 14 beats/min, p less than 0.001) occurred between 5 and 30 minutes (not 1 minute) before the onset of ischemia. A significantly higher heart rate at onset of ischemia was seen during Bruce protocol exercise testing than during daily life (117 +/- 12 versus 95 +/- 15 beats/min, p less than 0.01). However, when a less-strenuous, but more prolonged, exercise protocol was used in a subgroup of patients (n = 12), ischemia occurred at a heart rate that was significantly lower than during the Bruce protocol (88 +/- 14 versus 103 +/- 15 beats/min, p less than 0.05) and was not significantly different from the threshold heart rate at onset of ischemia during daily life (88 +/- 14 versus 84 +/- 12 beats/min, p = NS). As part of two placebo-controlled trials, treatment with both propranolol and nitroglycerin altered the distribution of ischemic events by heart rate but in opposite directions. Although propranolol largely eliminated events occurring at high (greater than 100 beats/min) and moderate (80-100 beats/min) heart rates, the number of events at low (less than 80 beats/min) heart rates was increased. In contrast, nitroglycerin reduced episodes at low and moderate heart rates only. CONCLUSIONS. Important increases in heart rate occur before the onset of ischemia during daily life, but this increase occurs much earlier than has been reported. Duration of heart rate increase appears to influence the heart rate threshold for ischemia, and this may contribute to the occurrence of ischemia at lower heart rates during daily life than during standard exercise testing. Last, different classes of drugs appear to have characteristic effects on ischemia occurring at different heart rates that may be useful in planning therapy.     

Long-term variation in myocardial ischemia during daily life in patients with stable coronary artery disease: its relation to changes in the ischemic threshold.

Long-term variation in the frequency of myocardial ischemia during daily activity in patients with coronary artery disease who do not experience symptomatic changes has not been documented. Because at one point in time, the magnitude of such ischemia is strongly related to the ischemic threshold measured during exercise testing, this study was undertaken to determine whether patients with stable coronary artery disease show long-term variations in the frequency and duration of myocardial ischemia and to establish whether such variability is related to parallel changes in the ischemic threshold during exercise testing. Forty consecutive patients (mean age 61 +/- 8 years) who showed a stable clinical course over greater than or equal to 12 months were studied with a repeat exercise treadmill test and ambulatory electrocardiographic (ECG) monitoring after withdrawal of antianginal medications. The ischemic threshold was determined as the exercise time at 1 mm of ST segment depression. The mean interval to both follow-up evaluations was 15 +/- 3 months. Among the 23 patients with myocardial ischemia on ambulatory ECG monitoring at initial evaluation, the number and duration of ischemic episodes at follow-up were increased in 5 patients (mean increase 3.6 +/- 2 episodes and 123 +/- 98 min), unchanged in 1 patient and decreased in 17 patients (mean decrease 2.6 +/- 2 episodes and 98 +/- 72 min). Of the 17 patients without ischemic episodes at initial evaluation, 3 had evidence of ischemia on follow-up ambulatory ECG monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)     

Active transient myocardial ischemia during daily life in asymptomatic patients with positive exercise tests and coronary artery disease

The management of asymptomatic patients with coronary artery disease (CAD) is controversial, and the level of "activity" of their CAD during normal daily life remains largely unknown. To examine this question, ambulatory Holter monitoring of ST segments was performed out of the hospital in 7 asymptomatic subjects with CAD during normal daily activities. Their condition was detected because they all had a silent positive exercise test and angiographically proved CAD. During a total of 384 hours of monitoring, 37 asymptomatic episodes of ST depression (1 mm or greater and lasting at least 30 seconds) were recorded in 5 of the patients. Most episodes (68%) were 10 minutes or less in duration but ranged from 1 to 253 minutes, and most (70%) had a maximal ST depression of 1 to 2 mm. A small increase in heart rate, ranging from 1 to 34 beats/min, preceded 65% of the episodes, but 35% were associated with no change or even a decline before the onset of ischemia. Fifty-four percent of the episodes occurred during rest or usual light physical activity, 8% during sleep and only 38% during exercise, including 1 prolonged bout while jogging. During 78% of the episodes, the subjects rated their mental activity as usual and only 14% occurred during mental stress. In addition, a distinct diurnal variation was noted with 57% of the ischemia occurring between 0600 and 1200 hours (p = 0.008). Therefore, most asymptomatic subjects had active transient ischemia during daily life, with many of the characteristics already described in symptomatic subjects with CAD.     

冠心病心电图心肌缺血与心率变异性的关系

为通过了解心肌缺血时心率变异性的改变，探讨冠心病自主神经失衡的状况，前瞻，顺序地观察静息心电图呈典型心肌缺血的冠心病患者２１例，心电图正常的冠心病患者１９例和健康人２２例ＨＲＶ时域，频域指标。     

Incidence of ventricular arrhythmias during transient myocardial ischemia in patients with stable coronary artery disease

To determine the incidence of ventricular arrhythmias related to episodes of transient myocardial ischemia during ambulatory electrocardiographic (ECG) monitoring, 97 patients with stable angina pectoris, angiographically proved coronary artery disease and an abnormal exercise test were studied. A total of 573 episodes with ST segment depression were documented: in 118 episodes (21%) the patients were symptomatic and in 455 (79%) they remained asymptomatic. Ventricular arrhythmias (greater than 5 premature ventricular beats/min, bigeminy, couplets or salvos of premature ventricular beats) occurred during 27 (5%) ischemic episodes in a subset of 10 patients (10%) (group A). The other 87 patients (90%) (group B) showed exclusively ischemic episodes without ventricular arrhythmias. Comparison of patients in group A and group B showed no differences in hemodynamic, angiographic, exercise testing and ambulatory ECG monitoring data. Ischemic episodes with and without ventricular arrhythmias showed a similar duration and amplitude of ST segment depression and a comparable heart rate at the onset of ischemia. Both types of ischemic episodes, with and without arrhythmias, occurred predominantly during the morning hours between 6:00 AM and noon, and both types remained asymptomatic to within similar percentages. The data demonstrate that ventricular arrhythmias are related to transient myocardial ischemia in only a few patients with stable angina pectoris; these arrhythmias are related neither to the degree of ischemia during ambulatory ECG monitoring nor to the occurrence of anginal symptoms.     

Triggers of myocardial ischemia during daily life in patients with coronary artery disease: Physical and mental activities,anger and smoking

Objectives. This study assessed the potency of physical and mental activities and emotions (anger and anxiety) and smoking and other substance use as proximate triggers of ischemia in patients with coronary artery disease during daily life.Background. Myocardial ischemia occurs during a wide variety of activities in patients with coronary artery disease, but frequency and relative potency of physical and mental activities, smoking and use of caffeine and alcohol as triggers of ischemia during daily life have not been established.Methods. Patients (n = 63) with coronary artery disease and evidence of out-of-hospital ischemia kept a validated structured diary of physical and mental activities and psychologic states while undergoing ambulatory electrocardiographic monitoring for 24 to 48 h.Results. Ischemia occurred most frequently during moderately intense physical and mental activities. Patients spent the largest proportion of time engaged in low intensity physical and mental activities (p < 0.05), but the likelihood of ischemia was greatest during intense physical (p < 0.0001) and stressful mental activities (p < 0.03). The percentage of time in ischemia was elevated and approximately equivalent for high intensity physical and high intensity mental activities (5%) compared with 0.2% when patients were engaged in low intensity activities. Strenuous physical activity (e.g., effortful walking, p < 0.05) and the experience of intense anger were potent ischemic triggers, and heart rates at onset of ischemia increased with the intensity of physical and mental activity and with anger. Among smokers, ischemia was more than five times as likely when patients smoked than when they did not (during 27% vs. 5% of diary entries, p < 0.0001). Coffee and alcohol consumption were also related to ischemia (p < 0.05), but this association disappeared after controlling for concurrent cigarette smoking.Conclusions. Triggers of ischemia in patients with coronary artery disease during daily life include not only strenuous exercise, but also activities involving low levels of exertion, such as anger and smoking. Mental activities appear to be as potent as physical activities in triggering daily life ischemia. Coffee and alcohol consumption are related to ischemia only by virtue of their associations with smoking.     

Sauna-induced myocardial ischemia in patients with coronary artery disease.

PURPOSE: Sauna bathing is a popular recreational activity that is generally considered to be safe. However, there have been case reports of adverse cardiac events. We sought to determine whether sauna use caused myocardial ischemia in patients with coronary artery disease. METHODS: Sixteen patients with proven coronary artery disease were submitted to three conditions (rest, exercise, and sauna bathing) with continuous electrocardiographic (ECG) monitoring and regular blood pressure measurements. During each condition, patients were injected with Tc-99 sestamibi followed by nuclear scintigraphic imaging. Perfusion defect scores were calculated in 15 patients. RESULTS: Sauna bathing was well tolerated. There was a mean (+/- SD) increase in heart rate of 32% +/- 20% in the sauna (resting mean heart rate = 60 +/- 9 beats per minute vs sauna mean heart rate = 79 +/- 11 beats per minute, P <0.001) and a 13% +/- 6% drop in systolic blood pressure (resting mean systolic blood pressure = 142 +/- 14 mm Hg vs sauna mean systolic blood pressure = 123 +/- 15 mm Hg, P <0.001). There were no arrhythmias or ECG changes in the sauna. Compared with rest, there was significant ischemia during sauna bathing (average perfusion defect score at rest = -0.44 vs average sauna score = -0.93, P <0.001). The perfusion defect score in the sauna was worse than the resting score in 14 of the 15 patients. Sauna-associated perfusion defect scores were highly correlated with exercise-induced scores (R2 = 0.65, P <0.001). CONCLUSION: In patients with stable coronary artery disease, sauna use is clinically well tolerated but is associated with scintigraphically demonstrated myocardial ischemia.     

冠心病患者无症状性心肌缺血与心率变异性的临床研究

目的探讨冠心病患者无症状性心肌缺血(SMI)的发生规律及与心率变异性的关系。方法应用24 h动态心电图分析206例冠心病患者发作心肌缺血情况并根据其是否伴有心绞痛,分为有症状性心肌缺血(Ⅰ组)和SMI(Ⅱ组),并与对照组进行心率变异性(HRV)对比。结果检出单纯SMI例数占冠心病心肌缺血例数的71%,SMI发作次数占心肌缺血次数的81.2%,SMI持续时间及ST段压低程度均显著高于有症状性心肌缺血,心肌缺血发作时间差异无统计学意义,高峰在06∶00~12∶00,00∶00~06∶00最少;各组HRV的特点:SMI时各时域指标依次减少,Ⅰ组、Ⅱ组与对照组比较,Ⅱ组与Ⅰ组比较,各参数差异均有统计学意义(均P<0.05)。结论SMI是冠心病患者心肌缺血最常见表现形式,心肌缺血改变了心脏自主神经调节的均衡性,而SMI的发生可能与心脏自主神经病变加重有关,SMI缺血程度、持续时间是引起急性心脏事件的重要因素。     

Biofeedback treatment increases heart rate variability in patients with known coronary artery disease

Objectives

To determine if cardiorespiratory biofeedback increases heart rate variability (HRV) in patients with documented coronary artery disease (CAD).

Background

Diminished HRV has been associated with increased cardiac morbidity and mortality. Evidence suggests that various lifestyle changes and pharmacologic therapies can improve HRV. The objective of this study was to determine if biofeedback increases HRV in patients with CAD.

Methods

Patients with established CAD (n = 63; mean age, 67 years) were randomly assigned to conventional therapy or to 6 biofeedback sessions consisting of abdominal breath training, heart and respiratory physiologic feedback, and daily breathing practice. HRV was measured by the standard deviation of normal-to-normal QRS complexes (SDNN) at week 1 (pretreatment), week 6 (after treatment), and week 18 (follow-up).

Results

Baseline characteristics were similar for the treatment and control groups. The SDNN for the biofeedback and control groups did not differ at baseline or at week 6 but were significantly different at week 18. The biofeedback group showed a significant increase in SDNN from baseline to week 6 (P < .001) and to week 18 (P = .003). The control subjects had no change from baseline to week 6 (P = .214) and week 18 (P = .27).

Conclusions

Biofeedback increases HRV in patients with CAD and therefore may be an integral tool for improving cardiac morbidity and mortality rates.     

Relation of heart rate dynamics to the occurrence of myocardial ischemia after coronary artery bypass grafting

Postoperative myocardial ischemia is a common finding after coronary artery bypass grafting (CABG) and is associated with an adverse short-term clinical outcome. The reasons and pathophysiologic background for the occurrence of ischemia after CABG are not well established. We tested the hypothesis that altered heart rate (HR) behavior precedes the onset of myocardial ischemic episodes in patients after CABG. Time-domain HR variability measurements, along with analysis of Poincaré plots and fractal scaling analysis were assessed in 40 CABG patients from 48-hour postoperative Holter recordings. Twenty patients experienced 195 ischemic episodes during the postoperative course. In the univariate analysis of HR variability measurements of the first postoperative day (POD), the increased ratio between the short-term (SD1) and long-term (SD2) HR variability analyzed from the Poincaré plot and the decreased short- and intermediate-term fractal scaling exponents alpha(1) and alpha(2) were significantly associated with ischemia during the study period (p <0.01, p <0.05, and p <0.05, respectively). In the multivariate model, the increased SD1/SD2 ratio of the first POD was the most powerful independent predictor of all possible confounding variables for the occurrence of postoperative ischemia (corresponding to a change of 0.15 U; odds ratio 2.2 and 95% confidence interval 1.2 to 5.7; p <0.01). Altered HR dynamics have been associated with myocardial ischemic episodes in patients after CABG, suggesting that the autonomic nervous system has an important role in the pathogenesis of myocardial ischemia in the postoperative phase of CABG.     

Transient myocardial ischemia during daily life in patients with syndrome X

Nineteen patients with syndrome X (typical exertional angina, positive exercise test response [at least 0.1 mV of ST-segment depression], no evidence of coronary spasm and angiographically normal coronary arteries) underwent continuous 48-hour electrocardiographic (ECG) monitoring during unrestricted daily life. Fifty-eight ischemic episodes of at least 0.1 mV of ST-segment depression were observed in the same ECG leads that showed ST depression during stress testing: 28 (48%) were accompanied by anginal pain and 30 (52%) were asymptomatic. No significant differences were found between painful and silent ST-segment depression with regard to the number of episodes, their temporal distribution, magnitude, duration or heart rate (HR) at onset of ST-segment depression. In the minute preceding ischemic ST shifts, HR did not change in 33% of episodes or increased by less than 10 beats/min in 28%. HR at onset of ST depression was significantly lower during ambulatory ECG monitoring than during exercise testing (98 ± 18 vs 117 ± 18 beats/min, p < 0.01). During ambulatory monitoring, 85 episodes of sinus tachycardia (exceeding by 10 to 80 beats/min the HR that triggered ischemia during exercise testing) occurred in the absence of angina or ST-segment shifts. The results of this study suggest that in patients with syndrome X, (1) myocardial ischemia frequently develops during daily life; (2) silent ischemia is an important component of this syndrome; and (3) increased oxygen demand in the presence of impaired coronary vasodilatory capacity is not the only cause of myocardial ischemia. Active mechanisms that transiently reduce coronary flow may act and explain occurrence of angina at rest and with minimal exertion.     

Anti-ischemic effects of amlodipine in patients with stable angina pectoris and myocardial ischemia during daily life. Amlodipine Study Group

Ambulatory electrocardiographic monitoring was used to assess the anti-ischemic effects of amlodipine in a subset of 56 patients enrolled in a 14-week withdrawal study; amlodipine therapy resulted in a marked decrease in the overall mean number of ischemic events and the average number of transient ischemic episodes (p <0.005). Amlodipine substantially reduced the number of ischemic events among all patients during the single-blind phase, with further significant reductions recorded among patients who remained on amlodipine during double-blind therapy, but the number of ischemic events increased almost to baseline levels in patients switched to placebo during double-blind therapy (p = 0.01 by analysis of variance).     

Sleep-disordered breathing and myocardial ischemia in patients with coronary artery disease

STUDY OBJECTIVES: To examine the occurrence of nocturnal myocardial ischemia and its relationship to sleep-disordered breathing (apneas and oxygen desaturations) in randomly selected men and women undergoing coronary angiography because of angina pectoris. DESIGN: An observational study using an overnight sleep study and Holter recording to examine disordered breathing (oxyhemoglobin desaturations > or = 4% and apnea-hypopneas), heart rates, and ST-segment depressions (> or = 1 mm, > or = 1 min). SETTING: University Hospital, Ume?, a teaching hospital in northern Sweden. PATIENTS: One hundred thirty-two men and 94 women referred for consideration of coronary intervention were randomly included, by lot. RESULTS: ST-segment depressions occurred in 59% (134 of 226) of the patients, and nocturnal ST-segment depressions occurred in 31% (69 of 226). A ST-segment depression occurred within 2 min after an apnea-hypopnea or desaturation in 12% (27 of 226) of patients. This temporal association was seen in 19% of nocturnal ST-segment depressions (71 of 366), more frequently in men (p < 0.01) and in more severely disordered breathing (p < 0.001). Most of these ST-segment depressions were preceded by a series of breathing events: three or more apnea-hypopneas or desaturations or both in 70% (50 of 71). CONCLUSION: Episodes of nocturnal myocardial ischemia are common in patients with angina pectoris. However, a temporal relationship between sleep-disordered breathing and myocardial ischemia is present only in a minority of the patients, but occurs more frequently in men and in more severely disordered breathing.     

Significance of silent myocardial ischemia during exercise testing in patients with coronary artery disease

To evaluate the significance of ischemic ST-segment depression without associated chest pain during exercise testing, data were analyzed from 2,982 patients from the Coronary Artery Surgery Study (CASS) registry who underwent coronary arteriography and exercise testing and were followed up for 7 years. Patients with proved coronary artery disease (CAD) (at least 70% diameter narrowing) were grouped according to whether they had at least 1 mm of ST-segment depression or anginal chest pain during exercise testing. Four hundred twenty-four had ischemic ST depression without angina (group 1); 232 had angina but no ischemic ST depression (group 2); 456 had both ischemic ST depression and angina (group 3); and 471 had neither ischemic ST depression nor angina (group 4). Sixty-three percent of patients in group 1 and 55% in group 2 had multivessel CAD (difference not significant). The 7-year survival rates were similar for patients in groups 1 (76%), 2 (77%), and 3 (78%), but were significantly better for patients in group 4 (88%, p less than 0.001). Among group 1 patients, survival was related to severity of CAD (p less than 0.001). The 7-year survival rate in group 1 was significantly worse than that in a separate group of 282 patients with ischemic ST depression without angina during exercise testing who had no CAD (95% survival, p less than 0.001). Thus, in patients with silent myocardial ischemia during exercise testing, the extent of CAD and the 7-year survival rate are similar to those of patients with angina during exercise testing. Prognosis is determined primarily by the severity of CAD. In patients without CAD, the survival rate is excellent.     

Exercise-induced myocardial ischemia in patients with coronary artery ectasia without obstructive coronary artery disease

BACKGROUND: Aetiology, clinical significance and treatment options for coronary artery ectasia/aneurysm is not clear. OBJECTIVE: We sought to determine whether exercise can induce coronary ischemia in patients with coronary artery ectasia/aneurysm without significant coronary stenosis. METHODS: Coronary artery ectasia was defined as 1.5-2-fold, aneurysm as >2-fold luminal dilatation of the adjacent normal segment. The study patients could have irregularities with ectatic coronaries but they did not have stenotic lesions >50% with visual assessment of two blinded observers. Patients having coronary artery ectasia or aneurysm with prior myocardial infarction, dilated cardiomyopathy, valvular heart disease, bundle branch block, significant ST-T changes were excluded. The control group was formed from a well matched population of 32 patients with normal coronary arteries who have not performed a treadmill test before coronary angiography. The study group underwent a symptom limited treadmill test if they did not have one before coronary angiogram, all control patients underwent treadmill test. RESULTS: Thirty-three patients with coronary artery ectasia/aneurysm (ranging from one to three vessels) but without significant stenosis were derived from 4470 cardiac catheterization procedures between January 1998 and July 2000. In the study group, 17 of the patients had positive treadmill tests with respect to five patients in the control group (P = 0.004). In subgroup analysis, diffuse ectasia/aneurysm (involving 2-3 vessels) was found to be strongly related with ischemia (P = 0.005) with respect to local disease. CONCLUSION: Coronary artery ectasia/aneurysm may lead to exercise induced ischemia, especially in the diffuse form.     

Role of myocardial oxygen demand in the pathogenesis of silent ischemia during daily life.

The role of myocardial oxygen demand in the pathogenesis of silent ambulatory myocardial ischemia was evaluated by reviewing and assessing the methods and results of recent studies. The performance of simultaneous ambulatory electrocardiographic and blood pressure monitoring in 25 men with proven coronary artery disease (CAD) revealed significant increases in heart rate and blood pressure (p < 0.001) preceding most silent ischemic events. By plotting the mean heart rate obtained at 5-minute intervals during the 30 minutes before an ischemic event, the ischemic heart rate was shown to be significantly higher (95 +/- 15 vs 74 +/- 11 beats per minute [bpm]; p < 0.01) than the nonischemic heart rate. The evaluation of heart rate changes during ambulatory ischemia (in patients with CAD and ischemia induced by an exercise test using gradual work load increments) showed a significant heart rate increase (> 10 bpm) at 1-5 minutes preceding the onset of ST-segment depression. Heart rate increases during exercise testing according to the gradual work load increments of the National Institutes of Health protocol were compared with the heart rate preceding ischemic events during daily life monitored by ambulatory electrocardiography and were found to be closely related. In contrast, heart rate increases that occurred during exercise testing using the standard Bruce protocol were higher and correlated less with those preceding ischemia in daily life. Heart rate and blood pressure increased significantly in most silent ischemic episodes, indicating that increased myocardial oxygen demand plays a significant role in the pathogenesis of myocardial ischemia during daily life.     

Comparison of heart rate variability and treadmill exercise score in patients with stable coronary artery disease

Depressed heart rate variability (HRV) is associated with increased mortality and morbidity with various forms of heart disease, and the Duke treadmill score (DTS) provides diagnostic and prognostic information for the evaluation of patients with coronary artery disease (CAD). Our study was aimed at assessing any possible correlation between HRV and DTS in stable CAD. We evaluated the correlation between the HRV assessed by using 24 hour ambulatory ECG monitoring, and treadmill exercise score in 37 patients with angiographically proven and clinically stable CAD. In univariate analysis, DTS showed a significant negative correlation with age (r=–0.89, p<0.01) and a significant positive correlation with the square root of the mean of the sum of the squares of differences between adjacent R-R intervals (RMSSD) (r=0.67, P<0.05), percent difference between adjacent normal R-R intervals >50 ms (PNN50) (r=0.69, P<0.05), and mean of the standard deviation of all R-R intervals in all the 5-minute intervals (HRVM) (r=0.63, P<0.05). There is no significant correlation between DTS and standard deviation of all R-R intervals (SDNN), standard deviation of the averages of R-R intervals in all 5-minute segments of the entire recordings (SDANN) and standard deviation of the SDNN in all the 5-minute intervals (HRVSD). In multiple regression analysis, age was the only independent significant predictor of DTS (p<0.01). DTS decreased with advancing age. SDNN, SDANN, RMSSD, HRVM and HRVSD were not apparent predictors for detecting of DTS. Age was an independent predictor of DTS. Although DTS was correlated with RMSSD, PNN50 and HRVM in patients with stable CAD, time domain parameters of HRV were not appearent predictor for DTS.     

Role of myocardial ischemia during programmed stimulation in survivors of cardiac arrest with coronary artery disease

The role of ischemia in the induction of ventricular tachycardia during programmed stimulation was studied in 19 patients who survived a cardiac arrest and were found to have a significant stenosis in at least one branch of the left coronary artery. The arterial-coronary sinus lactate difference was measured during electrophysiologic testing, before the induction of ventricular tachycardia. Ventricular tachycardia was induced in 15 patients; it was sustained and unimorphic in 6 patients and polymorphic in 9. Myocardial ischemia, as reflected by net myocardial lactate production, was present within 60 seconds before the induction of ventricular tachycardia in 8 of the 15 patients with inducible ventricular tachycardia. In 9 of the 15 patients, programmed stimulation was repeated after a 15 minute rest period, with the same coupling intervals that had induced ventricular tachycardia previously. Net myocardial lactate production was not present in any patient during this repeat attempt. In three patients without evidence of ischemia during the first induction of ventricular tachycardia, the arrhythmia was induced again by the specific coupling intervals that had induced it previously. However, in five of six patients with net myocardial lactate production during the first induction of ventricular tachycardia, the same coupling intervals that had induced the arrhythmia in the presence of ischemia no longer induced it in the absence of ischemia. The results of this study suggest that myocardial ischemia may be a requirement for the induction of ventricular tachycardia in some patients with coronary artery disease who survive a cardiac arrest.