Heart failure (HF) afflicts almost 5 million persons in the United States. A hallmark of HF is poor autonomic nervous system (ANS) control, especially high sympathetic (SYM) activity, which is linked to HF disease progression, dysrhythmias, and mortality risk. In a recent study, we found that HF is associated with severe gray matter injury in brain areas that control ANS outflow. These brain areas included the right and left insula, with the right insula more affected. However, it is unknown whether the extensive insular damage would be reflected in a larger HF sample, and it is unclear whether the right or the left insular injury is linked to the high SYM tone found in HF cases. The goals of this proposal are to determine whether the insular gray matter injury and abnormal reactivity to ANS challenges found earlier are reflected in a larger sample of HF patients, and if such insular injury is related to impaired SYM and/or parasympathetic (PS) outflow.
The specific aims of this study are to: 1) compare insular gray matter loss between HF and healthy controls using structural magnetic resonance imaging (MRI); 2) compare insular cortex responses in HF patients to SYM and PS components of ANS challenges (Valsalva maneuver and cold pressor) to healthy controls using functional MRI; and 3) correlate levels of plasma catecholamines to volume of insular injury in HF using structural MRI. The sample will consist of 80 subjects (40 HF and 40 age- and gender-matched healthy controls) who will undergo structural MRI, and physiological recording and functional MRI during ANS challenges with blood catecholamine analysis. We hypothesize that right insular damage will result in exaggerated catecholamine release, with more extensive levels related to greater damage, and that magnitude of PS physiologic effects will directly depend on extent of left insular injury. This study's findings will lead to a greater understanding of the relationship between central and peripheral autonomic nervous system activity in HF, and aid in the evaluation of the impact of central nervous system damage on HF disease status.

National Institute of Health (NIH)
National Institute of Nursing Research (NINR)
Research Project (R01)
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Nursing Science: Adults and Older Adults Study Section (NSAA)
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Huss, Karen
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University of California Los Angeles
Schools of Nursing
Los Angeles
United States
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Serber, Stacy L; Rinsky, Brenda; Kumar, Rajesh et al. (2014) Cerebral blood flow velocity and vasomotor reactivity during autonomic challenges in heart failure. Nurs Res 63:194-202
Pan, Alan; Kumar, Rajesh; Macey, Paul M et al. (2013) Visual assessment of brain magnetic resonance imaging detects injury to cognitive regulatory sites in patients with heart failure. J Card Fail 19:94-100
Kumar, Rajesh; Delshad, Sean; Woo, Mary A et al. (2012) Age-related regional brain T2-relaxation changes in healthy adults. J Magn Reson Imaging 35:300-8
Macey, Paul M; Wu, Paula; Kumar, Rajesh et al. (2012) Differential responses of the insular cortex gyri to autonomic challenges. Auton Neurosci 168:72-81
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Kumar, Rajesh; Woo, Mary A; Macey, Paul M et al. (2011) Brain axonal and myelin evaluation in heart failure. J Neurol Sci 307:106-13
Macey, Paul M; Woo, Mary A; Kumar, Rajesh et al. (2010) Relationship between obstructive sleep apnea severity and sleep, depression and anxiety symptoms in newly-diagnosed patients. PLoS One 5:e10211
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Kumar, Rajesh; Woo, Mary A; Birrer, Bramley V X et al. (2009) Mammillary bodies and fornix fibers are injured in heart failure. Neurobiol Dis 33:236-42
Woo, Mary A; Kumar, Rajesh; Macey, Paul M et al. (2009) Brain injury in autonomic, emotional, and cognitive regulatory areas in patients with heart failure. J Card Fail 15:214-23

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