Cardiac arrest and cardiopulmonary resuscitation dysregulates the hypothalamic-pituitary-adrenal axis

• Published in: Journal of cerebral blood flow and metabolism 2009-10, Vol.29 (10), p.1673-1682
• Main Authors: Neigh, Gretchen N, Karelina, Kate, Zhang, Ning, Glasper, Erica R, Owens, Michael J, Plotsky, Paul M, Nemeroff, Charles B, DeVries, A Courtney
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anxiety; Biological and medical sciences; Cardiac arrest; Cardiopulmonary Resuscitation - adverse effects; Corticosterone - blood; Corticotropin-Releasing Hormone; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care; Heart Arrest - complications; Heart Arrest - therapy; Hypothalamo-Hypophyseal System - physiopathology; Hypothalamus; Intensive care medicine; Medical sciences; Mice; Neurology; Pituitary-Adrenal System - physiopathology; Receptors, Corticotropin-Releasing Hormone - analysis; Receptors, Corticotropin-Releasing Hormone - metabolism; Time Factors; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2009.85

Cardiac arrest and cardiopulmonary resuscitation (CA/CPR) increase the risk for affective disorders in human survivors. Postischemic anxiety- and depressive-like behaviors have been documented in animal models of CA/CPR; however, the stability of post-CA/CPR anxiety-like behavior over time and the underlying physiologic mechanisms remain unknown. The hypothalamic–pituitary–adrenal (HPA) axis and the corticotropin releasing factor (CRF) system may mediate the pathophysiology of anxiety and depression; therefore, this study measured CA/CPR-induced changes in CRF receptor binding and HPA axis negative feedback. Mice were exposed to CA/CPR or SHAM surgery and assessed 7 or 21 days later. Consistent with earlier demonstrations of anxiety-like behavior 7 days after CA/CPR, increased anxiety-like behavior in the open field was also present 21 days after CA/CPR. On postoperative day 7, CA/CPR was associated with an increase in basal serum corticosterone concentration relative to SHAM, but this difference resolved by postoperative day 21. The Dexamethasone Suppression Test showed that the CA/CPR group had enhanced negative feedback compared with SHAM controls at postoperative day 21. Furthermore, there was a gradual increase in CRF1 receptor binding in the paraventricular nucleus of the hypothalamus and bed nucleus of the stria terminalis, as well as a transient decrease of both CRF1 and CRF2A receptors in the dorsal hippocampus. Therefore, sustained changes in activity of the HPA axis and the CRF system after CA/CPR may contribute to the postischemic increase in affective disorders.