Exposure to stressful situations produces physiological changes that lead to various somatic pathologies. For humans, most such situations involve stressors that are psychological in nature. We will study how various psychological and behavioral factors influence the development of stress-induced heat pathology in rats under carefully controlled conditions. The major focus of the proposal is on the effects of selected psychological variables, e.g. stressor predictability, availability of coping responses, conflict on myocardial pathology. Repeated exposure to stressors under these and other conditions will be given to determine whether the mechanisms that affect acute heat pathology are subject to habituation or to sensitization. We plan to detect and quantify stress-induced injury by means of a new technique that has proved in humans to be a most sensitive and specific indicator of acute heart damage. This technique is based upon the finding that heart muscle cells contain a form of the enzyme creatin kinase (CK), identified as the MB isoenzyme of CK, which is not present in significant quantities in other tissues. In most normal persons, the CK-MB isoenzyme is almost undertectable in serum; however, when cardiac muscle cells die, as during myocardial infarction, CK-MB is released and sifnificant quantities appear in serum. Moreover, serum levels of CK-MB are directly related to the amount of damaged heart tissue. With the sensitive techniques we have developed for the separation and measurement of CK isoenzymes, we have been able to show that unpredictable as opposed to predictable inescapable shock produces higher levels of CK-MB in plasma and greater myocardial necrosis. We will further delineate the nature of the myocardial pathology affected by this and other psychological variables with histologic and electrocardiographic measures. Within the context of the psychological models we have developed, we will measure several aspects of sympathetic activity as it affects the heart, with particular attention given to interaction with platelets, FFA, hyperlipidemic diets, and cardio-protective drugs.