Heart Failure and Sympathoexcitation

Dr. Scrogin’s research and that done by Renjun Wang, PhD; Qian Huang, MD; Rui Zhou, BSc; Zengxiang Dong, PhD; Yunfeng Qi, PhD; Hua Li, MS; Xiaowei Wei, MS; Hui Wu, MS; Huiping Wang, PhD; Christopher S. Wilcox, MD, PhD; Michael Hultström, MD, PhD; Xiaofu Zhou, PhD; and En Yin Lai, MD, PhD, both researched the behavioral influence that chronic heart failure can have in rats. Dr. Scrogin’s research focused on the anxiety like behaviors shown during the development of heart failure, while Dr. Wang, et al. focused on sympathoexcitation. Both studies illustrated increased activity in the sympathetic nervous system to be closely linked with damage and deterioration related to heart failure.

Dr. Scrogin performed coronary artery ligation (CAL) surgery and sham surgery’s eight weeks before the rats were tested using the echocardiography to determine the function of their left ventricles. Following that eight CAL rats and eight sham rats had their blood pressure, heart rate, ECG, and locomotor activity monitored by a telemetry probe implant throughout the testing cycle. The CAL rats developed congestive heart failure (CHF), which they determined through elevation in left ventricular pressure, a decrease in fractional shortening, and elevation in heart and lung/body weight ratios. The rats with CHF spent more time in the open arms of the elevated plus maze and two rats continuously jumped from the open arm. Both behaviors suggest increased anxiety in CHF rats due to their display of escaping behavior. None of the sham surgery rats displayed this escaping behavior. This data shows that suppression of the autonomic regulation due to the coronary artery ligation stimulates the progression of heart failure and increases the risk those with developing heart failure of have showing anxiety-like behaviors. This is likely due to a reduce threshold for panic from the suppression of the autonomic nervous system (Henze et al., 2008).

Dr. Wang et al. also performed coronary artery ligation surgery with the purpose of inducing CHF and sympathoexcitation to determine the pathway through which it occurs. Gene silencing and transferring in vivo was used to analyze the effects of knockdown on angiotensin II receptors (AT1R) and gamma-aminobutyric acid B-type receptor 1 (GABBR1) in the paraventricular nucleus (PVN). In vitro analysis was used to determine the concentration of norepinephrine (NE) in plasma and angiotensin II (AGNII) in the PVN. In animals with CHF it was found that there were higher expression of AT1R, homeobox D10 (HoxD10), and microRNA-7b (miR-7b) in the PVN and lower expression GABBR1. The increased miR-7b caused “sympathoexcitation in control animals and enhanced the changes in CHF” (Wang et al., 2015). GABBR1 expression normalized when an antisense miR-7b was infused, attenuating CHF symptoms and sympathoexcitation. It was found that in vivo knockdown of AT1R attenuated CHF symptoms, whereas, the overexpression of HoxD10 exaggerated CHF symptoms. “In vivo PVN ANGII infusion caused dose-dependent sympathoexcitation” that could be repressed by miR-7b and enhanced by GABBR1 silencing (Wang et al., 2015). This shows that there is a ANGII/AT1R/HoxD10/miR-7b/GABBR1 pathway in the PVN that is partially responsible for the deterioration of cardiac function and sympathoexcitation in CHF because AT1R stimulation of ANGII enhances sympathetic activity in the PVN by activating HoxD10, which increases miR-7b expression and decreases GABBR1 translation (Wang et al., 2015). 

Both Dr. Scrogin and Dr. Wang et al.’s research detailed the link between anxiety/sympathoexcitation and heart failure induced by coronary artery ligation. The vastly different approaches taken by each researcher perfectly demonstrates how collaborative the field of neuroscience is. Despite researching the same basic topic, Dr. Scrogin took a more behavioral approach determining the link, whereas Dr. Wang et al. used a more biochemical approach. Dr. Scrogin’s research showed that CHF increases the risk for anxiety by lowering the threshold for panic and Dr. Wang et al.’s research showed the biochemical pathway that is used in the suppression of the autonomic nervous system and reduction of the panic threshold.

Works Cited

Henze, M., Hart, D., Samarel, A., Barakat, J., Eckert, L., & Scrogin, K. (2008). Persistent alterations in heart rate variability, baroreflex sensitivity,and anxiety-like behaviors during development of heart failure in the rat. American Journal of Physiology: Heart and Circulatory Physiology,295, 29-38. Retrieved November 19, 2017.

Wang R, Huang Q, Zhou R, et al. Sympathoexcitation in Rats With Chronic Heart Failure Depends on Homeobox D10 and MicroRNA-7b Inhibiting GABBR1 Translation in Paraventricular Nucleus. Circulation Heart failure. 2016;9(1):e002261. doi:10.1161/CIRCHEARTFAILURE.115.002261. Retrieved November 19, 2017.