Episodes Of Silent Myocardial Ischemia Research Articles

Pathological Turbulence of the Heart Rhythm and Activation of the Antinociceptive System as Predictors of the Complicated Course of Silent Myocardial Ischemia in Patients with Post Infarction Cardiosclerosis According to the Data of Long-term Observation

To date, the issues of evaluating the course of silent myocardial ischemia (SMI) after a myocardial infarction (MI) taking into account risk factors (RF), evaluating the pathological turbulence of the heart rhythm, the state of activation of the body’s antinociceptive system, which necessitates an in-depth study of this pathology, remain unresolved, as well as new differentiated approaches to the treatment and rehabilitation of the modern category of patients. The objective: to analyze the features of the SMI course in patients with post-infarction cardiosclerosis depending on the RF. Identification of the interdependence between the degree of activation of the sympathoadrenal system and the features of the SMI course in patients with post-infarction cardiosclerosis, as well as the prognostic value for assessing the severity of the course of the disease. Materials and methods. The research was performed on the basis of the Ivano-Frankivsk Regional Clinical Cardiology Center (Ukraine). 154 patients with a silent form of coronary artery disease, which occurred in people with post-infarction cardiosclerosis, were examined. The diagnostic criteria were: episodes of SMI verified with the help of HM ECG and a test with dosed physical load. Results. Significant deviation of the ST segment which was detected during Holter monitoring of the ECG (HM ECG) in patients with SMI episodes does not mean that the absence of pain sensations in the presence of efferent nociceptive stimulation is a sign of the absence of ischemia and does not indicate an easier course of SMI compared to clinically manifest forms of CHD. The average concentration of β-endorphins in patients with lipid metabolism disorders was 4.01±0.02 ng/ml, in the presence of diabetes mellitus this indicator was equal to 4.68±0.03 ng/ml (р<0.01), and in persons with concomitant arterial hypertension it was 4.91±0.02 ng/ml (р<0.05). In subjects with two or more RFs, the similar indicator was the highest and amounted to 5.73±0.03 ng/ml (р<0.01). The point-biserial correlation coefficient was equal to 0.61 (р<0.05), which indicates a sufficiently high probability of the influence of the processes of activation of the antinociceptive system on the risk of myocardial infarction and unstable angina. Conclusions. It has been proven that the presence of postinfarction cardiosclerosis, type 2 diabetes mellitus, dyslipidemia, and arterial hypertension should be considered as factors that increase the risk of complications of coronary artery disease in patients with SMI. In the painless form of CHD, there is a probable increase in β-endorphins in the blood, which indicates the presence of pronounced afferent nociceptive stimulation, the intensity of which depends on the degree of myocardial ischemia. It has been proven that an increase of β-endorphins levels is associated with an increase in the risk of a complicated course of coronary heart disease in patients with silent myocardial ischemia. The presence in patients with SMI of myocardial ischemia, pathological turbulence of the heart rhythm, and activation of the antinociceptive system are extremely important for understanding the main links of the course of SMI and make it possible to base the approach to the therapy of such patients on a differentiated system algorithm that takes into account the discrepancy between the clinical manifestations of the disease and its real impact on coronary perfusion and the condition of the vascular wall.

Peculiarities of heart rhythm disorders in patients with myocardial infarction without elevation of ST segment depending on the degree of coronary artery lesions

Summary. The prevalence of myocardial infarction and its leading role in the structure of overall and cardiovascular mortality encourages the search for predictors of complicated course of disease and the search for optimal means to prevent adverse events. The aim of the study – to establish features of cardiac arrhythmias in patients with myocardial infarction without ST-segment elevation depending on the degree of coronary artery lesions. Materials and Methods. The study involved 156 patients with NSTEMI aged 38 to 80 years. All patients were examined according to the current treatment protocol for patients with acute coronary syndrome without ST segment elevation and daily Holter ECG monitoring was performed for 3-5 days after hospitalization. Results. It was found that the degree of coronary artery lesions is positively correlated with the likelihood of severe adverse ventricular arrhythmias and episodes of silent myocardial ischemia in the early period. Conclusions. By determining the total score of coronary artery disease, it is possible to stratify the adverse course of NSTEMI, in particular, the occurrence of fatal ventricular arrhythmias in the early period.

Results of Holter monitoring in patients with angina pectoris treated by combination of trimethazidine with fabomotisol in the area of former armed conflict

Aim. To assess the effectiveness of trimetazidine and fabomotisol adding to standard treatment in patients with stable angina in the area of former armed conflict in point of improving of Holter monitoring parameters.Material and methods. One hundred and twelve patients with stable angina of the II-III functional classes (FC) living in the area of former armed conflict were randomly divided into two groups. For 6 months 54 patients (control group) received standard treatment (isosorbide dinitrate 40 mg/day, metoprolole tartras 50-100 mg/day, acetylsalicylic acid 100 mg/day, simvastatin 40 mg/day). Fifty eight patients (study group) in addition to a standard treatment, took trimetazidine 70 mg/day and fabomotisol 30 mg/day. Initially and after 6 months they underwent Holter monitoring.Results. In patients of the control group the number of episodes of silent myocardial ischemia was statistically significantly reduced (p<0,05). The duration of episodes of silent and manifest myocardial ischemia, ST segment depression >1 mm, and the number of patients with supraventricular and ventricular extrasystoles decreased not statistically significant (p>0,05). The number of episodes of manifest myocardial ischemia did not change. In the study group, the number of silent ischemia episodes, the duration of silent and manifest myocardial ischemia significantly decreased. ST segment depression and the frequency of ventricular extrasystoles were also decreased (p<0,05). At the same time, the changes in number of supraventricular extrasystoles was not statistically significant (p>0,05). Conclusion. Using a combination of trimetazidine with fabomotisol in comparison with standard treatment in patients with angina reduces the frequency of angina episodes, the duration of myocardial ischemia, ST segment depression, the frequency of supraventricular and ventricular extrasystoles.

Silent Myocardial Ischemia as a Result of Cardiac Autonomic Neuropathy

to verify the effect of vegetative nervous system on the silent myocardial ischemia. We included in this study 56 patients with functional class II-III effort angina (22 men and 34 women, age 45-49 years) with silent myocardial ischemia (SMI). Examination included 24hour blood pressure and ECG monitoring. We revealed the interrelation between elevation of parameters of heart rhythm variability reflecting activity of parasympathetic nervous system and ST segment depression depth during episodes of SMI. Also, а significant interrelationship was found between SMI duration and degree of nocturnal diastolic blood pressure decrease which reflected parasympathetic nervous system activity. Silent myocardial ischemia more often occurred at the background of elevated activation of the parasympathetic nervous system.

The functional significance of vasomotor arteries dysfunction in the clinical assessment of myocardial ischemia in case of carbohydrate metabolism disorder

We investigated the relationship between the severity of silent myocardial ischemia and the functional state of arteries endothelium. We studied the significance of violations of vasomotor function with the loss of the ability to flow-dependent vasodilation as a risk factor, which increases the probability of the episodes of silent myocardial ischemia among patients with Type II DM. We observed 128 patients (66 male and 62 female), average age was 59,3±4,7. Each patient signed an agreement to take part in our research as a volunteer. The agreement was adopted by the local ethics committee.Patients with coronary heart disease and Type II DM had dominating daily duration of episodes of myocardial ischemia and a maximum depth of ST segment depression. Besides, they had reduced endothelium-dependent vasodilation reaction (EDVD=3,7±1,1%). The violation of the functional state of the vascular endothelium correlates with the registration frequency (R=-0,68; p

FRI0306 Favorable Effects of Rituximab Treatment on Lipid Profile, Arterial Stiffness, Carotid Atherosclerosis and Silent Myocardial Ischemia in Women with Rheumatoid Arthritis

ObjectivesTo study whether rituximab (RTX) modifies lipid profile, systolic (SBP) and diastolic (DBP) blood pressure, body mass index (BMI), blood glucose level, arterial stiffness (AS), carotid intima-media thickness (cIMT) and...

ARTERIAL ENDOTHELIAL DYSFUNCTION AND MYOCARDIAL ISCHEMIA IN PATIENTS WITH CARBOHYDRATE METABOLISM DISTURBANCES

Aim.To assess the role of vasomotor dysfunction and impaired flowdependent vasodilatation as a risk factor of silent myocardial ischemia (SMI) in patients with Type 2 diabetes mellitus (DM-2).Material and methods.The study included 128 patients (66 men and 62 women; mean age 59,3±4,7 years), who underwent Holter ECG monitoring, stress test (Bruce protocol), echocardiography, vascular ultrasound, and brachial artery endothelium-dependent vasodilatation (EDVD) assessment.Results.Patients with coronary heart disease and DM-2 demonstrated reduced EDVD levels (3,7±1,1%) and highly prevalent SMI (93,3%). There was a correlation between EDVD and the number (r=–0,68; p<0,05) or duration of SMI episodes (r=–0,53; p<0,01).Conclusion.Patients with DM-2 require the assessment of vasomotor endothelial function in order to predict cardiovascular complications. Coronary artery endothelial dysfunction, which manifests in inadequate vasodilatation in response to increased myocardial demand for oxygen, plays an important role in the ischemia development and progression.

Effect of nipradilol on silent myocardial ischemia and heart rate variability in chronic stable angina.

Silent myocardial ischemic episodes as well as decreased heart rate variability (HRV) indices are associated with an unfavorable outcome in patients with coronary artery disease. Nipradilol, which is a nonselective beta-adrenergic and nitrate-like vasodilator anti-anginal agent developed in Japan, may ameliorate silent myocardial ischemia, while it also improves exercise tolerance and HRV indices in patients with chronic stable angina. To investigate the effect of nipradilol (6 mg daily) on silent myocardial ischemic episodes and HRV indices, and to study its effect on the relationship between them, 24 patients with chronic stable angina underwent exercise treadmill testing and a 24-hour ambulatory electrocardiogram (ECG). The study protocol utilized a single blind, 4-week placebo-controlled design. The HRV indices from ambulatory ECG included mean RR (ms), SDNN (ms), SDANN (ms), SD (ms), rMSSD (ms), pNN50 (%); frequency analysis of HRV consisted of total (ms, 0.01-1.00 Hz), low (ms, 0.04-0.15 Hz) and high (ms, 0.15-0.40 Hz) components. Nipradilol significantly decreased the mean heart rate at submaximal and maximal exercise and the mean pressure rate product at submaximal and maximal exercise. It significantly improved exercise-induced maximal ST segment depression from -1.7 +/- 0.6 mm to -1.1 +/- 0.7 mm (p < 0.05). Silent myocardial ischemic episodes recorded during the 24-hour ambulatory ECG significantly decreased after nipradilol administration. Nipradilol also significantly influenced several HRV indices as well as the relationship between silent myocardial ischemic episodes and the HRV indices. Nipradilol significantly increased SD, rMSSD, pNN50, total spectra, low frequency spectra and high frequency spectra. In addition, nipradilol significantly decreased the LF/HF ratio from 1.7 (1.5-2.0) to 1.5 (1.3-1.8). These effects of nipradilol on HRV indices concomitantly occurred with the reduction in silent myocardial ischemic episodes. Nipradilol was found to effectively improve the episodes of silent myocardial ischemia as well as exercise-induced ischemia probably due to its beta-blocking properties and not nitrate-like actions. In addition, nipradilol also had a favorable effect on the HRV indices.

Silent Myocardial Ischemia and Late Ventricular Repolarization in the Genesis of Ventricular Fibrillation in Humans

BackgroundWe report a well‐documented case of a patient, a 62‐year‐old man, with severe and asymptomatic left main coronary artery disease who had several episodes of silent myocardial ischemia and a syncopal attack during Holter recording.Methods and ResultsAmbulatory monitoring showed isolated giant U waves separated from the T wave 60 minutes before syncope that was due to reversible ventricular fibrillation lasting about 4 minutes and spontaneously reverting to asystole (7 seconds) and then to atrial fibrillationConclusionOur experience suggests that myocardial ischemia may differently affect the repolarization times within the myocardium leading to widely disparate repolarization gradients that may represent the arrhythmogenic substrate for the occurrence of life‐threatening ventricular tachyarrhythmias. A.N.E. 1999; 4(2):250–254

Effect of carteolol on silent myocardial ischemia, variability in heart rate, and the pain-modulating system

To investigate the effects of carteolol, which is a nonselective beta-adrenergic agent with intrinsic sympathomimetic activity, on silent myocardial ischemia, exercise-induced myocardial ischemia, indexes of heart rate variability, and pain-modulating system, 20 patients (mean 60 +/- 9 years) with chronic stable angina underwent exercise treadmill testing and 24-hour ambulatory electrocardiographic monitoring during 2 weeks of carteolol administration (15 mg/day) in a double-blind, placebo-controlled design. Plasma levels of beta-endorphin and bradykinin and electrical pain stimulation to the skin were measured at rest and peak exercise. Indexes of heart rate variability of both time-domain and frequency-domain analysis were derived from 24-hour ambulatory electrocardiographic monitoring. Carteolol decreased maximal heart rate responses to daily activities during ambulatory monitoring and significantly reduced the median frequency and duration of silent myocardial ischemic episodes (from 1.0 to 0.0 events/24 hr and from 16 to 0 min/24 hr, respectively). Carteolol significantly decreased the rate-pressure product at rest and during exercise with improving maximal ST segment depression, suggesting amelioration of exercise-induced myocardial ischemia. Carteolol did not significantly affect plasma levels of beta-endorphin and bradykinin or pain threshold. It significantly decreased some indexes (standard deviation of all normal sinus R-R intervals in the entire 24-hour recording and standard deviation of the mean of all 5-minute segments of normal R-R intervals of a 24-hour recording) of heart rate variability. These results suggest that carteolol may reduce total myocardial ischemic burden by the reduction of cardiac oxygen demand during daily activities and exercise stress, while not affecting plasma levels of beta-endorphin, bradykinin, and pain threshold. Because carteolol tended to decrease indexes of heart rate variability, significant caution might be necessary in prescribing the beta-blocking agents with intrinsic sympathomimetic activity like carteolol to patients with potential serious arrhythmia.

Rationale for the use of calcium antagonists in the treatment of silent myocardial ischemia

Silent myocardial ischemia, whether it occurs at rest or during exercise, is associated with an unfavorable prognosis and may lead to sudden cardiac death. Agents used to treat silent myocardial ischemia have included nitrates, beta-blockers, and calcium antagonists (CAs). Despite treatment with traditional anti-ischemic agents, studies have shown that up to 40% of patients who receive what is considered to be clinically optimal antianginal therapy continue to have daily episodes of silent myocardial ischemia. The use of nitrates and beta-blockers is sometimes confounded by issues of tolerance and tolerability. Although the CAs have been found to be effective in decreasing the duration and frequency of episodes of silent ischemia, in general beta-blockers produce a greater reduction in these variables. Thus a need for effective and tolerable anti-ischemic agents persists. A new class of CAs, the tetralol derivatives, may show promise in this regard. The first of this new class, mibefradil, is characterized by selective blockade of T-type calcium-ion channels and has been shown in a few studies to reduce the frequency and duration of asymptomatic ischemic episodes in patients with stable exertional angina pectoris. Large-scale clinical trials are necessary before the efficacy and tolerability of this new CA can be compared fully with those of the beta-blockers and currently available CAs.

Effect of type A behavioral counseling on frequency of episodes of silent myocardial ischemia in coronary patients

Thirteen of 32 patients with coronary heart disease who also exhibited symptoms and signs of severe time urgency and hostility (the two overt components of type A behavior [TAB]) were found to exhibit multiple episodes of silent myocardial ischemia over a 48-hour period of Holter monitoring as indicated by electrocardiogram ST depressions. Ten of these 13 patients were given 14 months of TAB counseling in an attempt to diminish the intensity of their time urgency and hostility. The remaining three patients served as controls. After counseling, the intensity of the time urgency and hostility of the 10 counseled patients diminished 53% and 59%, respectively, as measured by the videotaped clinical examination. The time urgency and hostility of the three uncounseled control patients did not significantly change. The mean frequency of ischemic episodes in the 10 patients who received TAB counseling significantly declined from an initial 6.6 to 3.1 ischemic episodes per 24 hours. However, the mean frequency of ischemic episodes did not significantly decline in 2 of the 3 uncounseled patients. The third uncounseled patient developed a conduction defect in the 14-month interlude, making an analysis of his repeat 48-hour electrocardiogram for episodes of ST depression impossible.

Diagnosis of silent myocardial ischemia using ambulatory electrocardiographic monitoring with pedometer, analysis of heart rate, and ST loop in ambulatory electrocardiogram.

It has been suggested that episodes of silent myocardial ischemia (SMI) might influence the prognosis of patients with ischemic heart disease, as its consequences are similar to those of myocardial ischemia accompanied by pain. Ambulatory electrocardiogram (ECG) is generally employed in diagnosis as well as in evaluation of clinical efficacy in patients with SMI, but problems related to its application remain because of the difficulty in differentiating between nonischemic and ischemic ST-segment depressions and because of the absence of data concerning body movement. We developed a method for simultaneously recording onto magnetic tape both the ECG chart and pedometer count, as well as a program which enables semi-automatic analysis of the heart rate (HR)-ST relationship. This new method was employed to record ambulatory ECG along with pedometer count for a total of 70 patients, consisting of 53 with coronary heart disease who were shown to have ischemic heart disease, and 17 with various heart diseases in whom coronary angiography revealed no coronary stenosis. The HR-ST relationship was assessed for periods during which steps were recorded by the pedometer, that is, when patients were confirmed to have been under exertion effort. Patients demonstrating the following findings were diagnosed as true positive for SMI: the ST segment level did not decline until HR increased to a certain threshold, and the rate of change in the ST-segment level noted thereafter was -0.025 mm/beats/min or lower; or the ST-segment depression induced by effort continued even after discontinuation of exercise, after which time HR began to decrease, and the HR-ST loop consequently described a counterclockwise rotation. Evaluation of the HR-ST relationship based on these criteria revealed excellent results, as demonstrated by values of 79.2% for sensitivity and 94% for specificity. Our newly developed method of assessment of the HR-ST relationship via analysis of simultaneous data from an ambulatory ECG and a pedometer appears to be time saving, highly objective, and useful with regard to the diagnosis of SMI and evaluation of the therapeutic effect of drugs in patients with ischemic heart disease.

Effect of nipradilol on silent myocardial ischemia, plasma beta-endorphin, and bradykinin in chronic stable angina.

This study was undertaken to investigate the effect of nipradilol on the total ischemic burden and on plasma levels of beta-endorphin and bradykinin. Sixteen patients with chronic stable angina were subjected to exercise treadmill testing and 24-h ambulatory electrocardiogram (ECG). Nipradilol significantly decreased both mean heart rate and mean pressure rate product at submaximal and maximal exercise. It significantly improved exercise-induced maximal ST-segment depression from -2.7 +/- 0.5 mm to -1.3 +/- 0.6 mm (p < 0.05) and reduced the number of leads with significant ST-segment depression (4.0 +/- 1.2 vs. 2.0 +/- 1.8, p < 0.05). Silent ischemic episodes recorded in 24-h ambulatory ECG were significantly decreased by nipradilol administration, concomitantly with a decrement of mean heart rate and observed maximal heart rate. Patients with exercise-induced silent myocardial ischemia showed significantly increased plasma levels of beta-endorphin during both the placebo and nipradilol phases of the study. However, during the nipradilol phase, bradykinin did not change significantly at rest and at peak exercise. Nipradilol effectively controls exercise-induced myocardial ischemia and silent myocardial ischemic episodes, and does not influence the response of plasma levels of beta-endorphin to exercise stress testing in patients with exercise-induced silent myocardial ischemia.

Circulating α-actin in non-insulin-dependent diabetics with autonomic dysfunction

Silent myocardial ischemia in non-insulin-dependent diabetic patients occurs frequently in association with autonomic dysfunction, suggesting that diabetic neuropathy may be involved in the development of this disorder. Repeated episodes of silent myocardial ischemia can induce myocardial necrosis. Recently, actin was detected with Western blotting in the serum of patients with acute myocardial infarction and angina pectoris. We found that a large proportion of non-insulin-dependent diabetic patients with neuropathy also have detectable circulating concentrations of α-actin, and therefore suggest that the determination by immunoblotting of serum α-actin in such patients is an effective method to detect myocardial cell suffering and to identify patients that may need special consideration.

716-4 Placebo Treatment Reduces Both the Number of Ischemic Episodes and Duration of Ambulatory Silent Myocardial ischemia in Patients with Stable Angina Pectoris

Ambulatory silent myocardial ischemia occurs frequently in patients with stable exertional angina pectoris, It is widely accepted that a medication has antiischemic effects if it reduces either the number or the duration of silent myocardial ischemic episodes in comparison to pretreatment values. Effect of monotherapy with placebo on silent myocardial ischemia in 33 patients who took part in a parallel group investigational drug study and were assigned to the placebo arm of the study form the basis of this investigation. After discontinuation of all antianginal medications patients received two weeks of single blind placebo treatment followed by four weeks of double blind placebo treatment. Ambulatory holter monitoring was performed for 48 hours after two weeks of single blind placebo treatment and again after 4 weeks of double blind placebo treatment. The median value of silent myocardial ischemia attack rate during single blind placebo treatment was 7.2 episodes per 48 hours and decreased during double blind placebo treatment to a median rate of 3.1 episodes per 48 hours (P &lt; 0.004; 95% CI, -5.41, -1.0). Similarly the duration of silent myocardial ischemic episodes decreased by a median of 16,1 minutes per 48 hours (P &lt; 0,001; 95% CI. -35.7, -6.2 minutes) during double blind placebo treatment from a median value of 24.8 minutes per 48 hours during single blind placebo treatment. placebo monotherapy had a marked influence on ambulatory silent myocardial ischemia and reduced both the duration and number of silent myocardial ischemic episodes in patients with stable angina pectoris. These findings have important implications for interpretation of studies in which the effects of active treatment on silent myocardial ischemia are compared to baseline pretreatment values.

Effects of bepridil on silent myocardial ischemia and eicosanoid metabolism in chronic stable angina pectoris after healing of myocardial infarction

To investigate the effects of bepridil on silent myocardial ischemia and on eicosanoid metabolism, 10 patients with chronic stable angina underwent exercise treadmill testing and 48-hour ambulatory electrocardiographic monitoring both before and after 4 weeks of bepridil administration (150 mg/day). Fasting venous levels of thromboxane B 2, 6-keto-prostaglandin F 1α, and leukotriene C 4 were measured by radioimmunoassay. Bepridil decreased heart rate responses to daily activities during ambulatory monitoring, and significantly (p < 0.05) reduced the median frequency and duration of silent myocardial ischemic episodes (from 5.5 to 0 events/48 hours and from 86 to 0 minutes/48 hours respectively). Bepridil significantly decreased the blood pressure heart rate product at peak exercise and significantly prolonged the mean exercise tolerance time (from 456.6 to 527.0 second). Bepridil also significantly decreased the plasma levels of thromboxane B 2 and leukotriene C 4 at rest. These results suggest that bepridil may reduce silent myocardial ischemic episodes either by the reduction of cardiac oxygen demand during daily activities and exercise stress, or by controlling coronary and systemic vasomotor tone. The drug also has a salutary effect on eicosanoid metabolism, to which its efficacy on silent myocardial ischemic episodes may be related.

Usefulness of persistent silent myocardial ischemia in predicting a high cardiac event rate in men with medically controlled, stable angina pectoris

The presence of silent myocardial ischemia that persists after medical therapy for unstable angina identifies a subgroup at high-risk for cardiovascular events. 1–3 In addition, the presence of concomitant silent myocardial ischemic episodes in patients with angina pectoris appears to predict a higher risk of subsequent cardiac events. 4–7 This study was designed to determine the incidence, extent and prognostic significance of silent myocardial ischemia in patients with stable angina pectoris who have been rendered pain-free by medical therapy.

Effects of bisoprolol on the circadian distribution of silent myocardial ischemia and frequency domain parameters of heart rate variability

The autonomic nervous system is believed to play an important role in the occurrence of silent myocardial ischemia (SMI). To investigate the effect of bisoprolol on the circadian distribution of SMI and heart rate variability (HRV) we studied 5 patients with/> 4 episodes of SMI during 48 h Holter registration after a placebo run-in period. Patients were treated 4 weeks with bisoprolol 10 mg once daily. Spectral analysis of HRV was performed using a FFT algorithm, resulting in low frequency (LF, 0.04-0.15 Hz), high frequency components (HF, 0.15-0.40 Hz) and L F / H F ratio.

Effect of diltiazem on silent ischemic episodes, plasma bradykinin and prostaglandin metabolism

Plasma bradykinin and prostaglandin metabolism are related to the anginal pain modulating system in patients with ischemic heart disease. We carried out a placebo controlled single blind test of diltiazem (30 mg three times a day) in 15 patients with chronic stable angina. The effect of diltiazem was evaluated by exercise treadmill testing and 48-h ambulatory electrocardiographic monitoring. Plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1α levels were determined by radioimmunoassay prior to and during diltiazem therapy. Diltiazem significantly increased the exercise time and reduced episodes of angina. Diltiazem, however, did not appreciably improve either the frequency of silent myocardial ischemic episodes or the total duration of the silent myocardial ischemic episodes. Diltiazem also tended to decrease plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1α levels. When ischemic episodes on ambulatory electrocardiographic monitoring are categorized according to heart rate change at the onset of episode (type A, preceded by heart rate increase ⩾ 5 beats/min; type B, no preceding heart rate increase), diltiazem was only effective on type A ischemic episodes as well as on symptomatic ischemia. Further, bradykinin was significantly decreased by diltiazem only in patients with exercise-induced silent ischemia or no exercise-induced ischemia, while the thromboxane B2/6-keto-prostaglandin F1α ratio was unaffected by the administration of diltiazem. Thus, silent and symptomatic ischemia may be associated with different bradykinin and prostaglandin responses.