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 psychological and behavioral variables affect the development of heart pathology during stressful situations. We will use experimental design that permit us to assess, in laboratory animals (rats) under carefully controlled condition the influence of various psychological factors in stress-induced cardiac pathology. 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 on the finding that heart muscle cells contain a form of the enzyme creatine 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 undetectable in serum; however, when cardiac muscle cells die, as during myocardial infarction, CK-MB is released and significant quantities appear in serum. Moreover, serum levels of CK-MB are directly related to the amount of damaged heart tissue. We have developed sensitive techniques for the separation and measurement of CK isoenzymes in serum and tissues. We found that the CK-MB levels in rat serum are very low, as in humans, and are elevated by direct injury to the heart. In preliminary experiments we also found that stressful conditions produced significant elevations of CK-MB, suggesting that heart damage had occurred. After confirmation of the relationship of CK-MB and heart pathology by histological and ECG studies, we will develop the major focus of the proposal as to the effects of selected psychological variables, e.g., stressor predictability, availability of coping responses, conflict, on the release of CK-MB from heart in stressful conditions. Within the context of these psychological models we will examine the role of sympathetic factors influencing the uptake and turnover of norepinephrine in the heart, plasma catecholamines, and FFA. The effects of chemical sympathectomy, hyperlipidemia, cardioprotective drugs, and tolerance to other stressors will also be investigated.