Dr. Christopher West shares his research that investigates the cardiovascular and autonomic changes that occur following spinal cord injury as well as the efficacy of neuro-therapeutic interventions. Dr. West’s group uses small and large in vivo animal models to understand how the circuitry that controls the cardiovascular system changes following injury and what the downstream impact of these changes are for heart and blood vessel function. They also use these models to test the efficacy of novel therapies in the both the acute and chronic setting following injury. In the clinical and athletic spinal cord injury population, his group has conducted a number of mechanistic and applied studies to, 1) improve the understanding of how best to hemodynamically manage acutely injured patients, and 2) enhance the capacity of the cardiovascular system to enable an improved exercise response. This webinar introduces the major cardiovascular changes that have been characterized following spinal cord injury in animal models and the clinical population. Chris shares some exciting results from recent studies in which his group has tested the efficacy of novel therapies to improve cardiovascular function. Finally, he provides his outlook for the future of the field.

1. Copyright 2022. All Rights Reserved. Contact Presenter for Permission
Cardiovascular Pathophysiology in
the Setting of Spinal Cord Injury
Christopher West, PhD
Associate Professor
Cell & Physiological Sciences
The University of British Columbia

2. Partners and Sponsors
Proud to be a trusted research partner for leading academic
and industry groups around the world, Transonic Systems
specializes in:
• Biotelemetry
• Ventricular PV loops
• Blood pressure
• Vascular blood flow
• Tubing flow measurement
• Training & Application Support

3. Cardiovascular Pathophysiology
in the Setting of SCI
Christopher West, Ph.D.
Associate Professor (Cell & Physiological Sciences; Faculty of Medicine; UBC)
Research Scientist, Centre for Chronic Disease Prevention and Management
Principal Investigator, ICORD (International Collaboration on Repair Discoveries)
Heart and Stroke National New Investigator
Email: chris.west@ubc.ca
Tel: 250-807-8891

4. Today: A bi-directional translational Journey
1) History
2) Research program development
3) The human heart & SCI
4) Animal models
5) Acute interventions
6) Chronic treatments
7) Future visions

5. Part 1: The historical view of SCI

6. The historical/classical view of SCI
“An ailment not to be treated”
Stoke Mandeville – first spinal unit (1944)
Assinck et al (2017) Nature Neurosci. 20, 637–647 Cho et al (2019) Bioelectron Med. 5, 10

8. Autonomic disturbances

9. Interest is growing
~1000
~100
SCI+Autonomic
SCI+Motor

10. Part 2: Developing a translational program of
research to study the CV/Autonomic response to SCI

11. HR
Time
Start End
How did I get into this?

12. 0
20
40
60
80
100
120
140
Rest 40% 60%
Stroke
Volume
(ml)
Tetra
Para
Hopman et al. Eur J Appl Physiol Occup Physiol. 1992;65(1):73-8
0
5
10
15
20
Rest 40% 60%
Cardiac
output
(L/min)
Why is SV & HR so constrained during exercise in SCI?
Not the first time this has been shown

13. Translational integrative physiology lab
Research focus
Understanding the acute and chronic cardiorespiratory & autonomic consequences of spinal
cord injury (SCI)
Rat & Pig pre-clinical
models
Patient population
Elite athletic
population
ICORD, UBC; Vancouver
CCDPM, UBC; Kelowna

14. Outstanding trainees & staff!

15. Part 3: How does the human heart respond to
SCI?

16. Key findings:
In SCI compared to able-bodied
↓ left ventricular (LV) volumes
↓ LV dimensions
↓ LV mass index
= ejection fraction
1. Meta-Analysis of all echo studies in
the field
Williams et al. (2019) Heart. 105; 217-225

17. 2. Independent verification
Fossey & Balthazaar et al (2021) Nature Comms. 13, 1382.

18. Development of animal models to advance basic and
pre-clinical cardiovascular research

19. Development of clinically relevant outcomes
Saline
bridge
Body Wall
Splanchnic/Renal
nerve and Sheath
G1: Active Recording Electrode
G2: Reference
Electrode
BLOOD PRESSURE
sSNA
rSNA

20. Part 4: What have we learnt about the
physiology of SCI from these models?

21. 1. Reduced sympathetic nerve activity &
blood pressure
SHAM SCI

22. 2. Reductions in cardiac volumes
Fossey & Balthazaar et al (2021) Nature Comms. 13, 1382.

23. 3. Reductions in contractility
Fossey & Balthazaar et al (2021) Nature Comms. 13, 1382.

24. 4. Cardiomyocyte atrophy
Fossey & Balthazaar et al (2021) Nature Comms. 13, 1382.

26. Fossey & Balthazaar et al (2021) Nature Comms. 13, 1382.

27. Part 5: What can we do in the acute setting to
offset/treat cardiac dysfunction?

28. Acute setting
• Surgical decompression
• Cell therapies
• Appropriate hemodynamic management
*Courtesy of Dr. Brian Kwon

29. Does maintaining a higher BP improve
outcomes?
MAP of 85-90 mm Hg
x 7 days
1min recordings
~100 patients
>1M data points!
Hawryluk et al (2015) J Neurotrauma. 1958-67

30. MAP = Q x TPR
Q = SV x HR
Does maintaining a higher BP exacerbate
hemorrhage?
Cheung et al (2020) J Neurotrauma. 1958-67

31. Can the reduction in cardiac function act as a
novel hemodynamic management target?
Williams et al (2020) Nature Comms. 11. 5209

32. Can the reduction in cardiac function act as a
novel target?
Williams et al (2020) Nature Comms. 11. 5209

33. Current studies shifting focus to injury
epicenter vasculature
CONTROL DOBUTAMINE NOREPI
Impact on hemorrhage

34. Part 6: What can we do in the chronic setting
to offset/treat cardiac dysfunction?

35. 1. Intermittent hypoxia
Vose et al (2022), Exp Neurol. 347. 113891

36. 1. Intermittent hypoxia
AIH
10 min
Kim et al (2018), J Physiol. 596(15): 3217–3232
NON-SCI
10 min
AIH
SCI

37. 1. Intermittent hypoxia

38. 2. Epidural stimulation
West & Phillips et al (2018) JAMA Neurology. 75(5):630-632

39. 2. Epidural stimulation
POST-SCI POST-SCI+STIM

40. Part 7: What does the future of CV research
in the setting of SCI hold?

41. 1. Anatomical & Functional
Plasticity
2. Mechanism(s) of axonal
degeneration/regeneration
1. Cell Therapies
2. Scaffolds
3. Cord oxygenation &
secondary injury
1. Stimulation
2. Hypoxia/Hypercapnia
3. Activity based therapy
4. Combinational approaches
5. Behavioral change

42. Removing the potential confounding impact
of anesthesia

43. • SCI impairs bulbospinal control of SPNs that have downstream
impacts on the heart
• In the acute setting, a cardio-centric approach to hemodynamic
management may help to optimize cord oxygenation and offset
secondary injury mechanisms
• In the chronic setting, activating SPNs via either stimulation or AIH
appears capable of increasing cardiac function and improving BP
control
• Future studies should seek to target combinatorial strategies to
improve CV outcomes for the field of SCI
Conclusions

44. Mentors / Collaborators / Funders
Lee Romer
Brunel
“Dr K”
UBC
Brian Kwon
UBC
Kathleen Martin-Ginis
UBC
Wolf Tezlaff
UBC

45. 1. Exercise/activity based therapy
Cheung et al (2020) J Neurotrauma. 1958-67

46. SCI n=6
PHLC n=6
SCI
Stress echo
Cycling
-7 35
DAYS
SWIM n=6
Swimming
Echo
PV and
stress echo
Stress echo
A
B C
0 8 14
7
1. Exercise/activity based therapy
Cheung et al (2020) J Neurotrauma. 1958-67

47. 0
5 0
1 0 0
1 5 0
C O N
P
r
e
s
s
u
r
e
(
m
m
H
g
)
0
5 0
1 0 0
1 5 0
T 2 S C I
0 5 0 1 0 0 1 5 0 2 0 0 2 5 0
0
5 0
1 0 0
1 5 0
P H L C
V o lu m e ( L )
P
r
e
s
s
u
r
e
(
m
m
H
g
)
0 5 0 1 0 0 1 5 0 2 0 0 2 5 0
0
5 0
1 0 0
1 5 0
S w im
V o lu m e ( L )
E S P V R = 1 .4  0 .1 E S P V R = 0 .7  0 .1
E S P V R = 0 .7  0 .2
E S P V R = 0 .6  0 .2
1. Exercise/activity based therapy

48. How do SNS recruitment patterns impact
cardiac and vascular function?

49. Mechanisms of Epidural Stimulation

50. MAP is not a complete reflection of spinal
cord perfusion pressure (SCPP)
SCPP = MAP - CSFP

51. MAP CSFP SCPP

52. Thank you for participating!
CLICK HERE to learn more and
watch the webinar