The proposed 5-year research program will explore mechanisms of pain perception in patients with ischemic heart disease by the use of exercise stress, psychological stress, ambulatory monitoring and thermal pain testing. The following hypotheses will be tested: (1) Psychological stress is associated with greater elevations in plasma beta-endorphins than exercise stress and therefore more silent vs. painful ischemia. (2) Patients with silent myocardial ischemia have altered pain thresholds which are related to plasma beta-endorphin levels. (3) Patients who score high on depression scales but who are not clinically depressed frequently have more chest pain in association with myocardial ischemia and have suppressed beta-endorphin responses to behavioral stressors and exercise. Two laboratory test sessions on separate days, 48 hours of ambulatory electrocardiographic (amb-ECG) monitoring, the Rose Questionnaire assessing history of angina, and several instruments assessing psychological status will be administered to 130 patients with coronary artery disease and reproducible ischemia on exercise. These patients will represent 3 groups with predominantly painful, predominantly silent, or mixed ischemia. During one lab session, each pt will undergo exercise stress testing with radionuclide ventriculography (RNV); during the other he/she will undergo a continuous 15 minute psychological (public speaking) stressor, also accompanied by RNV. On both days, blood will be drawn for beta- endorphin levels before and after stress testing, and the patient's pain threshold and tolerance will be tested using a thermal probe. The patient will keep a detailed diary of symptoms and activities during the monitoring period. Endpoints for analysis will include: pain thresholds; pre-and post-stress beta-endorphin levels; hemodynamic values at rest, during exercise and the speech task; frequency and severity of ischemia during amb-ECG monitoring; prevalence and time to onset of psychologically induced and of exercise-induced ECG and radionuclide changes; ratings for depression, anger and coping; and prevalence and severity of anginal pain during amb-ECG monitoring, exercise and psychological stress testing.
