The long-term objectives of our research program are to model the pathophysiology of mental stress ischemia (MSI), and to use this model to test treatments that improve prognosis for the approximately 50% of CAD patients who are at risk for poor outcomes because of this ischemic syndrome. During the current funding period we have identified a network of brain regions, including prefrontal, sub-cortical and limbic areas, that serve executive, affective, attentional, and memory functions, and that is uniquely activated during mental vs. exercise related ischemia, and during laboratory stress in patients who are dispositionally prone toward hostility and anger. We have also found that perturbations in myocardial blood flow appear necessary for the provocation of MSI. Pilot data regarding, a) laboratory stress-induced changes in autonomic balance and associated increases in levels of the inflammatory cytokine TNF-a, and, b) the potentiating effect that threshold levels of ET-1 have on sympathetic activity in the provocation of MSI, provide a direction for the articulation of a complete "neurocardiac model" of this ischemic syndrome.
The aims of this proposal are to tie our observations regarding CMS activity to our observations regarding myocardial blood flow during mental stress by, 1) assessing key intermediary autonomic pathways during mental stress in patients with CAD, and 2) determining the contributions of dispositional (hostility) and reactive factors (state anger) to the provocation of ischemia during mental stress. Hypotheses relate to, a) MS induced alterations in autonomic tone, accompanying increases in levels of circulating vasoactive peptides (e.g., TNF-a, ET-1) and patterns of CMS activity during MSI;and, b) the relationship of dispositional factors to reactive factors in the prediction of MSI and the prediction of accompanying increases in levels of circulating vasoactive peptides during mental stress. Public Health Relevance: Mental stress ischemia is associated with increased risk of cardiac events and decreased survival. The complete modeling of this ischemia will help efforts to define and test treatments to reduce the risk of MSI and improve medical outcomes for patients with coronary disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059619-09
Application #
8102149
Study Section
Special Emphasis Panel (ZRG1-BBBP-T (02))
Program Officer
Stoney, Catherine
Project Start
1998-09-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
9
Fiscal Year
2012
Total Cost
$623,146
Indirect Cost
$143,064
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Burg, Matthew M; Soufer, Robert (2014) Psychological Stress and Induced Ischemic Syndromes. Curr Cardiovasc Risk Rep 8:377
Burg, Matthew M; Meadows, Judith; Shimbo, Daichi et al. (2014) Confluence of depression and acute psychological stress among patients with stable coronary heart disease: effects on myocardial perfusion. J Am Heart Assoc 3:e000898
Abisse, Saddam S; Lampert, Rachel; Burg, Matthew et al. (2011) Cardiac repolarization instability during psychological stress in patients with ventricular arrhythmias. J Electrocardiol 44:678-83
Burg, Matthew M; Soufer, Aaron; Lampert, Rachel et al. (2011) Autonomic contribution to endothelin-1 increase during laboratory anger-recall stress in patients with coronary artery disease. Mol Med 17:495-501
Burg, Matthew M; Martens, Elisabeth J; Collins, Dorothea et al. (2011) Depression predicts elevated endothelin-1 in patients with coronary artery disease. Psychosom Med 73:2-6
Fernandez, Antonio B; Soufer, Robert; Collins, Dorothea et al. (2010) Tendency to angry rumination predicts stress-provoked endothelin-1 increase in patients with coronary artery disease. Psychosom Med 72:348-53
Burg, Matthew M; Graeber, Brendon; Vashist, Aseem et al. (2009) Noninvasive detection of risk for emotion-provoked myocardial ischemia. Psychosom Med 71:14-20
Lampert, Rachel; Shusterman, Vladimir; Burg, Matthew et al. (2009) Anger-induced T-wave alternans predicts future ventricular arrhythmias in patients with implantable cardioverter-defibrillators. J Am Coll Cardiol 53:774-8
Soufer, Robert; Jain, Hitender; Yoon, Andrew J (2009) Heart-brain interactions in mental stress-induced myocardial ischemia. Curr Cardiol Rep 11:133-40
Lampert, Rachel; Soufer, Robert; McPherson, Craig A et al. (2007) Implantable cardioverter-defibrillator shocks increase T-wave alternans. J Cardiovasc Electrophysiol 18:512-7

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