1) Muscle undergoes significant structural and physiological adaptations after tendon rupture including radial and longitudinal muscle fiber atrophy, increased muscle fibrosis, and changes in passive muscle mechanics and stiffness. 2) Chronic rotator cuff tears result in retraction of the muscle from the bone, fatty infiltration of the muscle, and difficulty repairing the tendon. The muscle becomes insensitive to rehabilitation after chronic tearing. 3) Evidence suggests that after chronic tears, muscle function does not recover its normal relationship to structure. Changes in the extracellular matrix may underlie increased muscle stiffness observed after tearing.

1. 10/10/13
Physiological and Mechanical Adaptations of Muscle
to Tendon Rupture
Samuel R. Ward, PT, PhD
Associate Professor
Muscle Physiology Lab
Departments of Radiology, Orthopaedic Surgery, and Bioengineering
University of California San Diego
VA Medical Center San Diego
MuscleTech Network, Barcelona, Oct 15, 2013
Background
• Cuff injuries effect ~30% of people over 60 1
• 20-50% of repairs will fail 2
• Chronic tears
– Muscle retraction, fatty atrophy and fibrosis 3
– Nerve injury 4
– Difficult to repair 5
– High re-tear rates 2
– Insensitive to rehabilitation 6
Healthy
1
Lehman et al, Bull Hosp Jt Dis, 1995
Harryman et al, JBJS 1991
Gerber et al, JBJS, 2004
4 Costouros et al, Arthroscopy, 2007
5 Peterson, et al JSES 2011
6 Gerber et al, JBJS, 2000
2
3
Severe Tear
1

2. 10/10/13
Skeletal Muscle Hierarchy
Lieber, Skeletal Muscle Structure and Function, 2010
Muscle Force
Structure-Function Relationships
Muscle Length
Winters et al, J Biomech, 2012
Powell et al, J Appl Physiol, 1984
Bodine et al, J Neurophysiol , 1982
2

3. 10/10/13
Normal Architecture
Ward, et al Clin Orthop, 2006
30.0
PCSA (cm2)
25.0
Deltoid
Subscapularis
20.0
15.0
Infraspinatus
10.0
Supraspinatus
5.0
teres minor
0.0
0.0
2.0
4.0
6.0
8.0
Fiber Length (cm)
10.0
12.0
Ward, et al Clin Orthop 2006
Altobelli, et al, Submitted J Biomech 2013
3

4. 10/10/13
Pathology
Normal
Tear
47.72 mm
30.47mm
Anterior
Biceps tendon
SS tendon attached to Infraspinatus
and anterior capsule
Muscle Area Changes with Tear and Age (Human)
Barry et al, JSES 2012
4

5. 10/10/13
Muscle Structural Changes After Tear (Sheep)
Fat
Muscle
Gerber C, et al JBJS 2004
Muscle Fiber Length Changes After Tear (Human)
80
No Tear
Tear
Fiber Length (mm)
70
60
50
40
30
20
10
0
1
Tomioka et al, JSES 2009
5

6. 10/10/13
Architectural Adaptations to Tear and Nerve Injury
Relative Muscle Tension"
Sato, et al, In Submission JBJS
100"
80"
60"
40"
20"
0"
0.5"
1.0"
1.5"
2.0"
2.5"
3.0"
3.5"
4.0"
Sarcomere Length (µm) "
6

7. 10/10/13
Whole Supraspinatus Muscle Stiffness
Gerber et al, JSES, 1998- Human
Safran, et al, JBJS 2005- Dog
Gerber et al, JBJS 2004- Sheep
Human Passive Mechanics
Injured Cuff Elastic Modulus (kPa)
700
600
500
Supraspinatus
Infraspinatus
Control
*
400
300
200
100
0
Single Fiber
Fiber Bundle
Silldorff, Submitted JBJS
7

8. 10/10/13
Tissue Adaptations to Tear and Nerve Injury (rat)
Sato, et al, In Submission JBJS
Structural Change- Summary
Muscle Force
Healthy
Tear
Muscle Length
8

9. 10/10/13
Rabbit Lower Extremity Tenotomy
C:
TA
T:
TA
10 mm
C:
ED
L
T:
EDL
10 mm
C:
EDI
I
T:
EDI
I
10 mm
Active & Passive Mechanics
In Vivo Mechanical Testing
Tenotomy
&
Length-Tension Curve
Muscle Architecture
Fiber Area
Muscle Tension
Control
100 µm
Muscle Length
9

10. 10/10/13
Tenotomy Alters LT Relationship
Stress After Repair
Normalized Fiber Length [mm]
40
300
Control
Tenotomy
Control
Tenotomy
*
*
250
30
200
*
*
20
150
TA
*
*
100
10
50
0
0
TA
TA
EDL
EDL
EDII
EDII
EDL
EDII
* = p < 0.05
4000
250
*
Control
Tenotomy
6000
*
*
TA
200
Stress [kPa]
Passive Stiffness [kPa]
Tentomy Alters Passive Stiffness
2000
150
100
50
0
Control
Tenotomy
0
TA
250
EDL
0
EDII
EDL
40
Fiber Length [mm]
60
80
EDII
250
200
20
Stress [kPa]
Stress [kPa]
200
150
100
50
Control
Tenotomy
0
0
5
10
15
20
Fiber Length [mm]
25
30
150
100
50
Control
Tenotomy
0
0
5
10
Fiber Length [mm]
15
20
10

11. 10/10/13
ECM Remodeling
Control
Tenotomy
TA
50 µm
EDL
Winters, et al, In Progress
50 µm
50 µm
50 µm
EDII
50 µm
50 µm
New Histology Methods
H&E
Wheat Germ Agglutinin Picro-sirius Red
KI67
αSMA
Trichrome
Reticulin
pCEβ
Winters, Buck et al, In Progress
11

12. 10/10/13
Human Muscle Gene Expression
Choo, McCarthy et al, In Progress JBJS
Summary
• Structural Changes
– Radial and longitudinal atrophy
• Physiological Changes
– After chronic tears, function does not follow structure
– Evidence for ECM changes leading to muscle stiffness
• Rehabilitation
– Massive tears in the shoulder don’t appear to recover
12

13. 10/10/13
Faculty
Doug Chang, MD- UCSD
Adam Engler, PhD- UCSD
Don Fithian, MD – Kaiser
Larry Frank, PhD- UCSD
Jan Fridén, MD- Göteborg, Sweden
Christian Gerber, MD- Balgrist, Switzerland
Eric Hentzen, MD, PhD- UCSD
John Lane, MD- Coast Surgery Center
Rick Lieber, PhD- UCSD
Hiro Okuno, MDJoseph Sarver, PhD- Penn
Simon Schenk, PhD- UCSD
Lou Soslowsky, PhD- Penn
Andrea Taylor, PhD- Duke
Steve Thomopoulos, PhD- Wash U
Students
Grant Altobelli, MD – Tufts
Geoff Abrams, MD- Stanford
Alex Choo, MD- UCSD
Carolyn Eng, BS- Harvard
Ki Lee, MD- Yonsei
Meagan McCarthy, MD- UCSD
Randy McKnight- UCSD
Morgan Silldorff, MD- UCSD
Gretchen Meyer, PhD- UCSD
Eugene Sato, BS- UCSD
Ana Rodriguez-Soto, BS- UCSD
13