1. Is the sympathetic nervous system overactive in cancer? Ashika Sequeira Hayward House Nottingham City Hospital

2. Is the sympathetic nervous system overactive in cancer? Why this project? Aims Method Results and discussion

3. Why this project? Unique - Directly grounded in clinical medicine - improving therapeutic intervention for patients - Working with subset of specialised patients in palliative medicine

4. Cachexia What is it? -Paraneoplastic syndrome characterised by weight loss, anorexia and asthenia - Key metabolic alterations - Changes in energy expenditure and immune function - How many patients affected? - Pathophysiology not fully understood

6. The sympathetic nervous system Potentiating pro-inflammatory state exacerbates cachexia COPD, CHF are also associated with cachexia Autonomic dysfunction (increased sympathetic, decreased vagal) present Could similar process be occurring in cachexia? Could it lead to pharmacological treatment of cachexia?

7. Method Systematic recruitment: 10 patients with cancer and >5% weight loss 10 age-matched healthy volunteers Matched inclusion/ exclusion criteria Measured SNS activity using HRV Biochemical markers: serum cortisol, serum C-RP, 24-hr urinary catecholamines and metanephrines

8. Heart Rate Variability Natural variation in heart rate mediated by physiological mechanisms

9. Heart Rate Variability Power Spectral Analysis Splits oscillations into components by frequency VLF, LF, HF LF = sympathetic activity HF = parasympathetic activity

10. Patients (n=9) Healthy Volunteers (n=9) Z valueSignificance of difference (p value) Total Power (ms²)336 (318)772 (1835)-1.720.09 Low Frequency (ms²) 62 (93)148 (701)-1.950.05 High Frequency (ms²) 104 (101)313 (530)-2.070.04 Low Frequency : High Frequency 0.74 (2.02)0.88 (1.06)-0.300.77

11. Discussion Consistent with reduced parasympathetic and sympathetic activity Unexpected result In keeping with previous HRV work in AIDS Unlikely to be overactivity of SNS Is SNS depressed? Secondary parameters were not significantly different Significantly reduced parasympathetic function

12. In summary This study shows evidence of autonomic dysfunction in cancer patients However, no significant difference between patients and healthy volunteers in other parameters Limitations of this study Further work indicated

13. Thank you! Any questions?