tissue device interaction

1. ANASTOMOTIC INTIMAL
HYPERPLASIA
Shraddha Dahal

2. ANASTOMOSIS
 An anastomosis is the surgical connection between two tube-like structures or
passageways in the body.
 Examples of surgical anastomoses are:
• Arteriovenous fistula(an opening created between an artery and vein) for dialysis.
• Colostomy(an opening created between the bowel and the skin of the abdominal wall).
• Intestinal, in which two ends of intestine are sewn together.
• A connection between a graft and a blood vessel to create a bypass.
2

3. VASCULAR GRAFT FOR
ANASTOMOSIS
 A vascular graft is used to redirect blood flow from
one area to another by reconnecting blood vessels.
 It is required if the blood vessels are diseased or
blocked.
 Atherosclerosis-blood vessels become narrower by
the accumulation of fat, cholesterol, calcium and
other substances.
 Types:
I. Natural- autograft (taken from person’s own
vein)is preferred, allograft(taken from different
person’s vein).
II. Synthetic- Dacron(Polyethylene
terephthalate),Teflon(Polytetrafluoroethylene),etc.
3

4. INTIMAL HYPERPLASIA
 Intimal hyperplasia is the process in which the intima becomes thickened due the
presence of vascular smooth muscle cells and proteoglycan-rich extracellular matrix
located between the endothelium and the internal elastic lamina.
 It occurs due to various injuries that always involve some endothelial damage.
 The migration and proliferation of smooth muscle cells are provoked by vascular
wall injury, inflammation and stretch.
 It leads to thickening of the vessel wall and narrowing of the lumen.
 Blood flow is reduced that eventually lead to thrombosis of whole blood vessel and
causes myocardial strokes if the thrombi travels to smaller blood vessels.
4

5. Fig. Healthy vessel VS Vessel with IH
5

6. ANASTOMOTIC INTIMAL
HYPERPLASIA
 The vessel and a graft used as anastomose differ in
various properties such as elastic properties ,
composition, haemodynamic factors like shear stress
which lead to anastomotic intimal hyperplasia.
1. VSMC proliferation in the media:
• Normal endothelium produces factors like prostacyclin
and heparin sulphate , which inhibit VSMC proliferation.
• Damaged endothelium produces less heparin sulphate,
and heparinolytic enzymes released from thrombocytes
further decrease its concentration.
6

7. • When endothelial cells are damaged , thrombus formation is induced. Within 24
hours after thrombus formation proliferation of VSMC(Vascular Smooth Muscle
Cell) occurs.
• Moreover, when the endothelium is damaged the production of other VSMC
proliferation-inhibiting factors like NO(Nitric Oxide) and natriuretic peptides by the
endothelium will decrease.
• Basic fibroblast growth factor(bFGF) which is released by dying or damaged EC and
VSMC, stimulate VSMC proliferation.
• Thus, damage of the vessel wall decreases production of growth-inhibiting factors
and increases the expression of growth stimulating factors that shifts the balance
towards VSMC proliferation.
7

8. 2.VSMC migration from media to intima
• VSMC are embedded in ECM which includes the basement membrane, inner elastic
lamina and the interstitial matrix.
• The inner elastic lamina is produced by the EC and the interstitial matrix is produced by
the VSMC. The ECM is continuously changing by altered pattern of matrix synthesis
and by the action of matrix metalloproteinases(MMPs).
• MMPs play important role in wound healing by modifying the wound matrix , allowing
for cell migration and tissue remodeling.
• An intact ECM prevents VSMC migration but the injury induces production of different
plasminogen activators, which degrade the ECM and activate MMPs. All the growth
factors like BFGF(basic fibroblast growth factor), PDGF and TGF-ß increase after injury
and in turn increases plasminogen activators.
8

9. • Because of the damage of ECs, production of heparin sulphate is decreased and it ends
the inhibition of plasminogen production.
• Also fibroblast growth factors significantly contribute to the medial proliferation of
VSMC, while the presence of PDGF(platelet derived growth factor) promotes migration
to the intima.
3. Intimal expansion
• It occurs as a result of VSMC accumulation through proliferation, continued migration,
or both , as well as exuberant ECM synthesis.
• The VSMC accumulation process and volume of ECM production appears to be tightly
linked ,with a fairly constant proportion of VSMC to ECM volumes, characterizing the
intimal lesions that arises after a variety of vascular injuries.
9

10. • The proportional contribution of VSMC and ECM volume to the overall intimal
volume remains constant except directly below the endothelium where both VSMC
proliferation and the relative proportion of VSMC are higher.
• Not much is known about the control of matrix production in the intima.
• Growth factors such as TGF-ß and PDGF stimulate ECM production by VSMC.
• Thus, the same factors that stimulate VSMC proliferation simultaneously increase
production of ECM.
10

11. AIH IN VENOUS AND PROSTHETIC
GRAFTS
11

12. • In normal circulation, a vein is subjected to low pressure, non-pulsatile flow and a shear
stress of around 0.2 dyne/cm^2. When vein is used as graft in the arterial system, the vein is
exposed to a high pressure, pulsatile flow and a shear stress of approx.3-6 dyne/cm^2.
• Alteration in shear stress influence the expression of endothelial adhesions.
• Arterialised vein grafts obtained from humans in the early postoperative period(<24 hours)
show loss of endothelial cells , particularly at the peri-anastomotic area, and fibrin deposition
on the intima.
• This results in the loss of endothelium dependent relaxation to acetylcholine and diminished
contraction to serotonin.
• Vein grafting is followed by a rapid decomposition of leukocytes, platelets and other blood
components which can release cytokines that may influence VSMC proliferation and
migration leading AIH.
12

13. • In prosthetic grafts, the development of IH follows the sequence:
1. Early thrombosis
2. Phagocytosis of thrombi
3. Appearance and proliferation of fibroblasts in the pseudo-intima(a new layer formed
on the intimal surface of blood vessel graft or vascular prosthesis, consisting the cells
other than ECs or proteins such as plasma proteins or collagen)
4. Appearance and extension of ECs
5. Appearance of VSMC
6. Intimal hyperplasia by proliferation of fibroblasts and production of collagen fibrils
• In contrast to healing in injured arteries, thickening of intima in vascular grafts occur
beneath the endothelial layer. Hence, it supports the conclusion that ECs might serve as
a source of growth factors.
13

14. • However , PTFE grafts can initiate the production of VSMC growth factors in
various ways:
1. Zones of flow separation and low shear are present around the anastomosis that
causes platelet adherence and activation which leads to the release of growth
factors.
2. Turbulence occurs around the anastomosis causing endothelial cell damage. As a
result growth factors are released by ECs.
3. Compliance mismatch at the anastomosis may lead to excessive stretching of the
VSMC that causes VSMC to proliferate.
4. Foreign body response activates macrophages which excrete growth factors.
14

15. SITES OF AIH
1. Suture line
2. Floor of the artery
 Suture line intimal thickening:
 Can be observed in all PTFE and vein anastomoses(greater in PTFE).Develop at the graft-vessel
wall junction: in the sinus, at the toe, and at the heel of the anastomose.
 It may represent vascular healing and remodeling in response to mechanical injury or compliance
mismatch.
 Arterial floor intimal thickening :
 Develops in the region opposite the distal portion of the graft hood.
 It has been noted in 12 of 14 anastomoses. 2 anastomoses where it is absent: PTFE and vein
• Since, the replication of the self-renewing endothelial surface has been very difficult which
recognizes the prosthetics as a foreign body even when it is incorporated well. It is the major reason
of the graft failure. 15

16. Fig. Sites of anastomotic intimal hyperplasia
16

17. REDUCTION OF AIH
• A number of different anastomosing techniques have been developed in which
venous material is used in a transverse orientation to create a gradual transition of
elastic properties and to facilitate the anastomosing of vessels of different diameter
and wall structure.
17

18. THANK YOU!
18