1. Altered HRV fractal dynamics after spinal cord injury as function of lesion level Paolo Castiglioni 1, Carolina Gambirasio 2, Giampiero Merati 1 1 IRCCS Fondazione Don C. Gnocchi, Milan, Italy 2 Osp. Niguarda Ca’ Granda, Milan, Italy

2. Self-similarity is expected in CV signals because “complex systems” produce self-similar signals West GB et al (1997) Science The CV is “complex” because: it is a fractal network of branching tubes connecting several vascular beds interacting each other through local and global regulatory mechanisms

3. The ANS plays a major role in the integration and coordination of local vascular regulation Hypothesis methods of fractal analysis should detect alterations in the ANS integrative control better than spectral methods

4. AIM to evaluate whether an altered autonomic integrative control is better identified by fractal- rather than by spectral-analysis of HRV. This will be done by calculating HRV power spectra and fractal spectra of scale coefficients in spinal-cord injured (SCI) individuals with lesion level below T4, i.e., the 4 th thoracic (T) vertebra. These SCI individuals represent a model of altered autonomic integrative regulation, in presence of an intact cardiac sympathetic and vagal heart-rate control.

5. F(n) ÷ n  11 22 Temporal Spectrum of Scale Coefficients  (  )

6.  (  p )=  '(n p ) with  p =n p /f HR Temporal Spectrum of Scale Coefficients  (  )

7.  [s] Temporal Spectrum of Scale Coefficients  (  ) 68 healthy volunteers: M ±SEM

8. Temporal Spectrum of Scale Coefficients  (  )  [s] 68 healthy volunteers: M ±SEM

9. Power Spectrum 68 healthy volunteers: M ±SEM

10. Data Collection ECG recorded sitting at rest for 10’ in: 1)Able-bodied (AB) controls: N=34 2)Spinal cord injured (SCI) subjects: N=28 (Lesion Level between T 5 and L 5 ) SCI SCI H (T 5 and T 11 ) N=14 SCI L (T 12 and L 5 ) N=14 AgeBMIF/M AB39.3 (12.1)24.7 (2.6)5/29 SCI H 37.1 (6.6)24.6 (4.1)1/13 SCI L 40.9 (10.0)25.5 (4.8)2/12 M (SD)

11. AB vs SCI L ABSCI L P VLF 2.83 (0.40)2.94 (0.34)0.34 LF 2.84 (0.51)2.81 (0.41)0.84 HF 2.28 (0.45)2.25 (0.46)0.83 log 10 ms 2 ; m (sd) AB SCI L

12. AB vs SCI L  (s) Student’s T  5% 1% AB SCI L

13. AB vs SCI H ABSCI H P VLF 2.83 (0.40) 2.74 (0.40) 0.48 LF 2.84 (0.51) 2.50 (0.64) 0.06 HF 2.28 (0.45) 2.03 (0.52) 0.11 SCI H AB

14. AB vs SCI H  (s) Student’s T  1% 5% AB SCI H

15. Conclusions SCI L. When the lesion compromises the vegetative control of vascular beds lower than the splanchnic district,  reveals alterations that go completely undetected in the HRV power spectrum.  Fractal analysis is more sensitive than power spectral analysis in revealing alterations of the integrative control of the ANS. SCI H. When the lesion compromises higher vascular beds (splanchnic districts included), both the fractal and the power spectra of HRV are altered. PSD: reduction of the 0.1 Hz oscillation. (explained by the hypothesis of the “baroreflex resonance”)  altered over a broad band of scales (short and long  ) Power- and fractal spectra provide complementary information helpful for better detecting alterations in the integrative control of the ANS

16. Berger RD et al. Transfer function analysis of autonomic regulation. Canine atrial rate response. Am J Physiol. 1989 Vagal outflow k1k1 RRI  V (t)=0.5  RRI (t)=0.5  S (t)=0.5  k 2  if t>>T=60 s  RRI (t)=0.5  k 2 /s if t<<T=60 s  RRI (t)=1.5 Sympathetic outflow k 2 ------------ s+1/T RRI T=60 s

17. V SCSC SVSV Atropine x V SCSC SVSV Propranolol x N=9 healthy volunteers resting supine Autonomic Blockades and  (t) Castiglioni et al (2011) J Physiol

18. Autonomic Blockades and  (t)