This is a resubmission of a proposal for continuing support to utilize the model provided by the denervated heart of human cardiac transplant recipients to test an elaboration of the psychophysiological reactivity hypothesis of coronary artery disease (CAD). The hypothesis that the intact cardiac autonomic control system is required to buffer increases in blood pressure variability in response to psychological challenge will be tested. Recent evidence suggests that blood pressure variability is a risk factor to cardiac disease independent of mean arterial pressure. It is hypothesized that diminished cardiac autonomic control permits elevated challenge-induced blood pressure variability responses which in turn are associated with increased risk of CAD. Beat-to-beat heart period and blood pressure and arterialized plasma norepinephrine will be measured in 28 cardiac transplant recipients and equal-sized samples of age- and gender-matched normal control and renal transplant subjects during a quiet resting baseline and in response to mental arithmetic and Stroop color-word tasks. Cardiac autonomic control, operationalized as heart period variability, and blood pressure variability will be computed by established time series methods. The absence of cardiac autonomic control, as indicated by virtual absence of heart period variability, is well-established in cardiac transplant recipients. It is predicted that due to this greatly reduced cardiac autonomic control, psychological challenge will lead to significantly greater increases in low frequency blood pressure variability in cardiac transplant recipients compared to the other two groups and that this difference will be stable over the first year following transplantation. Cardiac transplant recipients represent the most dramatic case of diminished cardiac autonomic control and, therefore, the clearest test of this hypothesis. However, the hypothesis is relevant not only to cardiac transplant patients, in whom the development of CAD is greatly accelerated compared to the population as a whole, but also in individuals with intact cardiac nerves but reduced cardiac autonomic control. These include patients with depression, anxiety disorders, and diabetic neuropathy, as well as healthy individuals high in hostility, all of whom have increased risk of CAD. Thus, although in this application, only cardiac transplant recipients and appropriate control groups are studied, support for this hypothesis is relevant to many populations, healthy and otherwise, with reduced autonomic control.
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