Remodelling Ability of living tissue to adapt to its environment
by changing its shape and structure Modifies mechanical properties
Driven by tendency to maintain optimal levels of stress and strain
Slide 2 The Response of Conduit Arteries to Chronic Changes in
Pressure and Flow Remodelling: Chemical Cellular Morphological
Slide 3 If material added to outer surface: Wall thickness by 19%
Lumen area remains constant Circumferential stress by 16% Can
sustain pressure of 16% Hypertrophy Suppose cross sectional area of
media increases by 20% If material added to inner surface Wall
thickness by 21% Lumen area by 4% Circumferential stress by 19% Can
sustain pressure of 19% Slide 4 If material moves from inside to
outside: Wall thickness by 2% Lumen area 4% Circumferential stress
by 4% Can sustain pressure of 4% Rearrangement Suppose 20% of
material moves, but cross sectional area of media remains constant
If material moves from outside to inside: Wall thickness by 2%
Lumen area by 4% Circumferential stress by 4% Can sustain pressure
of 4% Slide 5 SMOOTH MUSCLE WAVE REFLECTION HEART WORK MATERIAL
STIFFNESS STRUCTURE ELASTIC RESERVOIR PERIPHERAL RESISTANCE
FUNCTIONAL STIFFNESS GEOMETRY h / R JUNCTIONS/ DISEASE E inc E p Z
C CHEMICAL COMPOSITION Pulsatile Steady Consequences of remodelling
Slide 6 Physiological Perinatal changes in: Pulmonary artery/aorta
Aortic scleroprotein Internal/external iliac Distribution of
intercellular junctionsPathological Hypertension Atheroma Growth
retardation in early life P.S.D. Ageing Residual stress Large/small
vessel differences in: Elasticity Scleroprotein Causes of
Remodelling Slide 7 Pig pulmonary artery Slide 8 Slide 9 1000100101
0.2 0.4 0.6 0.8 1.0 1.2 1.4 Pressure Flow Age (hr) P and Q/Wt
(relative to 1h values) 1D2D4D1W2W4W Slide 10 Slide 11
8006004002000 0 10 20 30 40 Pulsatile Steady Total Age [hr] Right
Heart Power [mW/kg] Slide 12 3 days3 months Slide 13 Pathological
remodelling of arteries l Pressure (circumferential stress or
strain) VSMC hypertrophy and or hyperplasia Collagen (Elastin)
synthesis l Flow (shear stress or strain) Endothelial cell mediated
VSMC migration and proliferation Intimal hyperplasia and
hypertrophy l Mechanical damage Combination of the two factors
above Acute or chronic Slide 14 Shear Stress ( Q/r 3 ) less
shearIntimal hyperplasia radius Stress normalised Q Change in flow
Change in lumen radius Optimal shear stress 15 dyne cm -2. (Glagov,
S. et al. Frontiers of Medical & Biological Engineering, 1993.
5: 37-43.) Slide 15 Slide 16 Post stenotic dilatation Slide 17
Slide 18 Silver, super glue and X-rays Slide 19 Slide 20 Topical
application of nor-adrenalin before freezing Slide 21
Nor-adrenaline after freezing Slide 22 Distal/Proximal Time since
treatment [days] Ring Freeze Freeze + Ring Slide 23 Circumferential
Stress (= Pr/h) Increased stretch Synthesis of protein etc. wall
thickness Stress normalised P Change in Pressure Change in medial
thickness Slide 24 Is there a relationship between the severity of
hypertension and the degree of remodelling? Slide 25 Methods l 30
four week old male Wistar rats l Left renal artery clipped,
contralateral kidney untouched l Caudal artery systolic pressure
measured using tail cuff and optical sensor Three measurements made
on separate days between 4 and 5 weeks after clipping, then
averaged l Animals killed at age 9 weeks.Vasculature fixed at
pressure of 100mmHg Slide 26 l Tissue samples taken from Thoracic
aorta (5mm distal to 4th intercostal space) Abdominal aorta ( 5mm
proximal to external iliac branch) Right renal artery l Paraffin
embedded l 5m sections cut and stained Millers elastic stain for
morphometry Ehrlichs haematoxylin for counting cell nuclei Slide 27
Medial cross sectional area VSMC in outer half VSMC in inner half
of media Lumen cross sectional area Medial thickness Mean values
derived from measurements on 4 rectangular areas shown Morphometry
Slide 28 Slide 29 Medial thickness (mm) 0.02 0.04 0.06 0.08 0.10
0.12 0.14 1 00120140160180200220240260 Abdominal aorta Right renal
artery Thoracic Aorta p < 0.004 p < 0.003 p < 0.002 Caudal
artery systolic BP (mmHg) Slide 30 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
0.8 0.9 100120140160180200220240260 Thoracic Aorta p < 0.0002
Abdominal aorta p < 0.05 Right renal artery p < 0.0008 Medial
cross-sectional area (mm 2 ) Caudal artery systolic BP (mmHg) Slide
31 Slide 32 100120140160180200220240260 0.15 0.20 0.25 0.10 0.30
Thoracic Aorta NS Abdominal aorta p < 0.02 Right renal artery NS
Mean circumferential stress MNm -2 Caudal artery systolic BP (mmHg)
Slide 33 0 1000 2000 3000 4000 100120140160180200220240260 Number
of cells per 5m section Abdominal aorta Right renal artery Thoracic
Aorta Caudal artery systolic BP (mmHg) Slide 34 0 10 20 30 40 50 60
Number of cells/ 5m section TAAARR Vessel Outer half Inner half
Slide 35 Summary & Conclusions Vascular response - hypertrophic
in nature Correlates with the severity of hypertension No
hyperplasia No difference in cell numbers between inner and outer
halves of the aortic media Circumferential stress increases non
significantly with hypertension in thoracic aorta and renal artery
Significant increase in abdominal aorta Shear stress remains
constant?
