Evaluation of peripheral vascular disease

Acute limb ischemia:  a sudden decrease or worsening in limb perfusion leading to potential threat to limb viability.

Causes-                               

1.       Embolization

2.       In situ thrombosis

3.       Occlusion of bypass graft

Patient presentation in acute limb ischemia-

1.       Severe pain in limb

2.       Coldness

3.       Numbness

4.       Loss of movement

5.       Discoloration (Mottling)

Sign and symptoms-

·         Pallor

·         Temperature

·         Sensation and movements

·         Arterial pulsations

·         “Disappearing pulse”

Most common presentation- claudication, pre gangrene

Thrombus stops at bifurcation-

·         Carotid bifurcation

·         Aortic bifurcation

·         Brachial bifurcation

·         Femoral bifurcation

·         Popliteal bifurcation

Acute on chronic limb ischemia - [pathomechanism] - if a plaque ruptures (fractures) then it settles on various , underneath surface of fractured plaque is thrombogenic, helps in thrombosis formation,- thrombosis embolizes.

Risk factors:    atherosclerosis- brain:stroke   ;heart:heartattack  ; leg : legattack  (gangrene)

Prevention of amputations:

·         Stop smoking

·         Exercise regularly

·         Control of blood pressure

·         Control diabetes

·         Eat healthy food

At least:

·         Careful daily inspection by diabetics/ high risk groups

·         Do not ignore pain on walking/ non healing wounds/ blue-black toes/ fingers.

Clinical examinations:

·         Pulses-  Dorsalis pedis artery, Posterior tibial artery, Popliteal artery

Diagnostic modalities:

·         Hand held Doppler (A.B.I.)-

·         Colour coded Duplex scan

·         CT Angiography

·         3D contrast MR Angiography

·         Digital substraction angiography

Acute limb ischemia

v  Severe pain in legs with cold blue toes

v  Severe pain in arms with cold blue fingers

v  Numbness

v  Common after angina/ MI

v  Treatment: urgent embolectomy with thrombolytic therapy

Stem cell therapy in peripheral vascular disease- a novel approach

Regeneration

Buergers disease (TAO)- it is characterized by blockage of medium and small blood vessels, mostly in the legs, sometimes in the arms.

·         Tobacco use

·         Under 45 years

·         Segmental occlusion

·         Small and middle sized blood vessels affected

·         Inflammatory cellular infiltrate within thrombuss

·         Involvement of surrounding venous tissues

Conventional surgical wisdom does not work:-

1.       These patients are always young

2.       Concomitant superficial thrombophlebitis

3.       Endovascular interventions difficult

4.       Lumbar sympathectomy

5.       Experiment treatment modalities (omentopexy and Ilizarov)

(Hence the need for alternative therapies)

Bone marrow derived progenitor cell transplantation can be tried as a ‘last resort’ in these patients.

Protocol for treatment:-

1.       Risk factor modification

2.       Medical management

3.       Endovascular management

4.       Surgical management

5.       Stem cell therapy

Therapeutic angiogenesis in patients:

1.       Therapeutic angiogenesis- an attempt to relieve inadequate blood flow by the directed growth and proliferation of blood vessels.

2.       Complex process involving multiple growth factor, receptors, extra cellular signalling pathways and local and bone marrow derived cells

Therapeutic angiogenesis in patients   [Mechanism]:

1.       Angiogenesis- formation of endothelial lined blood vessels

2.       Vasculogenesis- formation of endothelial lined blood vessels with periendothelial matrix and smooth muscles

Therapeutic angiogenesis in patients:

-          Adult human stem cells are intrinsic to various tissues:-

o   Haematopoietic stem cells are the best characterized adult stem cells.

o   Capable of maintaining, generating and replacing terminally differentiated cells

o   They can differentiate into cells beyond their own boundaries- ‘Developmental Plasticities’

-          The “Daunting task” facing a committed stemcell:-

o   Should home into right place

o   Attain necessary shape, set up correct contacts

o   Perform functions of adult tissues

o   Adopt to differentiate cellular environments

Major type of stem cells:-

A.      Embryonic stem cells

a.       From blastocysts leftover from in vitro fertilization in the laboratory

b.      From aborted foetuses

B.      Adult stem cells

a.       Stem cells have been found in the blood, bone marrow, liver, kidney, cornea, dental pulp, umbilical cord, brain, skin, muscle, salivary glands.

Source of stem cells:-

A.      Autologous bone marrow- heterogeneous stem cells- haematopoietic stem cells, mesenchymal stem cells, multipotent adult progenitor cells, EPC and ? other yet – unknown factors.

B.      Peripheral blood stem cells- mobilized into peripheral blood by cytokine administration; GCSF (granulocyte colony stimulating factor) mobilized stem cells used for organ regeneration- ? effective

Studies:

-          Preclinical studies have shown that injection of bone marrow mono nuclear cells – {including endothelial progenitor cells} into ischemic limbs- increases collateral vessel formation

Transplantation of peripheral blood stimulated mononuclear cells-

-          Pre-treatment with G-CSF (Filagastrim) increases endothelial progenitor cells in bone marrow and peripheral blood

-          There is increased release of progenitor cells in circulation which are picked up and used for auto transplantation

-          Adverse reactions to G-CSF are rare but following are documenting- rare cause of splenic rupture, ARDS, Arterial thrombosis

-          The patient will continue to receive the standard therapy for CLI in the form of antiplatelet agents, anticoagulants, cilastazole, antibiotics, pain-killers, local care, and dressing of wounds and other treatments as required.

Methodology-

                Transplant group

o   S/c inj. of r-GCSF 600mcg/day- 5 days

o   LMWH prophylaxis

o   CD 34+ counts X days 3

o   Peripheral blood harvested from stem cells

o   30-50ml cell suspension collected

Procedural details

o   Regional anaesthesia

o   20 guage needle

o   0.75ml/ injection sie

o   Gastrocnemius muscle

o   Distance between injection site- 1cm

Limitations

o   Exact mechanism not known

o   Protocol  not standardized

o   Long term results

o   Need for randomized controlled trial

Summary:

-          Use of peripheral blood mononuclear cell autologous transplantation into ischemic limbs to prevent amputation appears to be a variable therapeutic alternative in patients with non reconstructable peripheral vascular disease.