Power point presentation about general principles of organ transplantation and pioneer surgons and investigators, Specific discussion about Heart, Heart lung and Lung transplantation is given

1. Organ Transplantation
(Heart & Lung Transplant)
Dr R S Dhaliwal
MBBS,M.S.,DNB(Surgery).M.Ch,DNB(CTVSurg)
FACS,FCCP,FNCCP,FICA,FICAS
Former,Prof & HOD, CTV Surgery, PGIMER Chandigarh

2. Introduction
• Organ transplantation is the moving of an
organ from one body to another or from a
donor site to another location on the patient's
own body, for the purpose of replacing the
recipient's damaged or absent organ
• The emerging field of regenerative medicine is
allowing scientists and engineers to create
organs to be re-grown from the patient's own
cells (stem cells) or cells extracted from the
failing organs

3. Introduction
• Earliest transplant- 300 AD Christian Arab Saints
Cosmas and Damian reported to have replaced
diseased leg of a patient with normal leg from a
dead person
• 1901-10 Jaboulay and Alex Carrel developed techniqu
es of vascular suturing and anastomosis
• 1954-Joseph Murray, Boston USA , First kidney
transplant in world between identical twins
Got Nobel prize in 1990
• 1962- Roy Calne , U.K. –introduced Azathioprine for
prevention of rejection of kidney allograft
• 1963 – Tom Starzl , USA- First Liver transplant

4. Alex Carrel Roy Calne

5. Joseph Murray Tom Starlz

6. Miles stones in organ transplantion
• 1966-Tom Starlz et al ,USA- Used ALG –anti lymphocyte globulin
for immunosuppresion
• 1966- Lillehei & Kelly,USA- First human pancreas transplant
(with kidney transplant
• 1967-Christiaan Bernard,South Africa- First heart transplant
• 1968-Friz Derom-Belgium- first lung transplant
• 1969- Geof Collins- Developed solution for organ preservation
• 1974- Sutheranland & Najarin USA- First human pancreatic islet
transplant
• 1978-Roy Calne,UK- Introduced Cyclosporine
• 1981-Reitz & Shumway USA-First heart lung transplant
• 1981-Ben Cosini et al- Monoclonal antibody OKT3
• 1987-Foker Belzer et al- Univ. of Wisconsin solution
• 1989- Tom Starzl- introduced FK506 (tacrolimus)
• 1995- Lloyd Ratner et al –Laproscopic living donor
nephercectomy

7. Transplant -Definitions
• Allograft- An organ or tissue transplanted from one
person to another
• Isograft (Syngeneric) graft- A transplant between two
identical twins
• Orthotopic graft- A graft placed in its normal
anatomical site
• Heterotopic graft- A graft placed in a site different
from its normal site
• Xenograft- A graft between two species
• Alloantigen- Transplant antigen
• Alloantibody- Transplant antibody
• HLA – Human leukocyte antigen , the main trigger of
graft rejection

8. Graft Rejection
• ABO blood group antigens- recipients should receive a
graft that is ABO compatible. Permissible transplants
are- -Group O donor to Grp O,A,B or ABO rcpt
-Group A donor to Grp A or AB rcpt
-Grp B donor to Grp B or AB recipient
-Grp AB donor to Grp AB recipient
• HLA antigens- are most common cause of graft
rejection, act as antigen recognition units
HLA –A,-B(Class I ) and –DR(class II) are most
important In organ transplant
Anti HLA antibodies may cause hyperacute
rejection

9. Graft Rejection
• Allografts act as powerful antigen resulting in
rapid graft rejection which can be controled by
immunosuppressive therapy
• Studies done by Peter Medawar in 1940-50
proved that allograft rejection was due to an
immune response,not an inflamatory esponse
• Later studies showed that T lymphocytes play an
essential role in graft rejection mechanism
• Allografts produce graft rejection due to histo
compatibility antigens which are of three types -
-ABO blood group antigens
-HLA human leukocyte (major antigens)
- Minor HLA antigens

10. Types of Graft rejection
• Hyperacute rejection-
Immediate graft destruction due to ABO or
preformed anti HLA antibodies, intravascular
thrombosis occurs
• Acute rejection-
Occurs during first 6months mediated by T cell
dependent immune response.Reversible
Characterise mononuclear cell infilteration
• Chronic rejection-
Occurs in first 6months.Most common cause of
graft failure.Myointimal proliferation in graft arteries
causing ischemia and fibrosis.Non immune factors
may also be responsible in pathogenesis

11. Causes of allograft dysfunction
• Early- Primary non function(irreversible ischemic
damage)
• Delayed function(reversible ischemic injury
• Hyperacute and acute rejection
• Arterial or venous thrombosis of graft vessels
• Drug toxicity(cyclosporine and tacrolimus)
• Infection (CMV disease in the graft)
• Mechanical obstruction (ureter/CBD)
Late- -Chronic rejection -Arterial stenosis -
Recurrance of original disease in the graft -
Mechanical obsruction(ureter,CBD)

12. Immunosuppressive agents
• Azathioprine- Prevents lymphocyte proliferation
• Mycophenolate mofetil- Prevents lymphocyte
proliferation
• Cyclosporin- Blocks IL-2gene transcription
• Tacrolimus –Blocks IL-2 gene transcription
• Rapamycin-Blocks IL-2 receptor signal
transduction
• OKT3 mAb – Depletion and blockade of T cells
• ALG/ALS- Depletion and blockade of lymphocytes
• Anti CD25 mAB- Targets activated T cells
• Corticosteroids – potent anti inflamatory effect

13. Side effects of immunosuppressive drugs
• Steroids- Hypertension,Diabetes,osteoporosis
dyslipidemia, Cushingoid appearance
• Azathioprine- leucopenia,thrombocytopenia,
hepatotoxicity,GIT symptoms
• Cyclosporin- Nephrotoxicity,hypertension,dyslipidemia
hirsutism,ginigival hyperplasia
• Tacrolimus-Neurotoxicity,diabetes,hypertensio
nephrotoxicity,dyslipidemia
• ALG – Leucopenia, thrombocytopenia
• OKT3 – Pulm Oedema,leucopenia,cytokine release syn.
• Sirolimus- Thrombocytopenia, dyslipidemia
• Mycophenolate mofetil-GIT symptoms,leucopenia,
Thrombocy topenia

14. Complications of immunosuppression
• Infection- High risk of viral infetions
-Bacterial and fungal infections common
-Highest risk in first 6 months after transplant
–Chemoprophylaxis important in high risk pts
-Virus infection due to reactivation of latent virus
or primary infetion
-Cytomegalovirus infection is major problem
-Early diagnosis and prompt treatment is must
–Pre-transplant vaccination for community
acquired infections should be considered
• Malignancy- -PTLD-Post transplant lymphoproli
ferative disease and Kaposi ‘s sarcoma
- High risk of squamous carcinoma of skin

15. Organ donation and procurement
• Most organs for transplant are obtained from brainstem dead, heart
beating cadaveric donors , multiple organs are procured
• In kidney transplant live donors and arrested heart cadaveric donors are
common
• Acceptable donor age- Kidney -2 yrs to no upper age limit
Liver – No age limit - Heart -0 to 65 yrs
Lung – 0 to 60 yrs -Pancreas-10-50yrs
• Donor organ should be free from primary disease and infection
• Organs are procured through midsternotomy (heart & lungs ) and
midline laparotomy (liver,pancreas & kidneys). Organs are perfused in
situ and after removal with –heart with cold cardioplegia solution, lungs
with University of Wisconsin UW sol. Liver with UW sol, kidneys and
pancreas with Euro- Collins sol.
• Various organs can be stored for different period after cold perfusion
Kidney - 24-48hrs Liver 12-24hrs Pancreas -10-24hrs
Small intestine 4-8hrs Heart 3-6hrs Lung 3-8hrs

16. Evaluation of potential recipients
• Evaluation by multidisciplinary team including a
surgeon and physician
• Presence of comorbid factors (DM,CAD,Renal or
Liver dysfunction, uncontroled HTN)
• Exclude systemic sepsis and malignancy
• Psychologically normal for transplan and
immunotherapy
• Any pre-operative surgery required
• Evaluate for organ specific criteria for transplant
• Optimise recipient condition prior to transplant

17. Organ function after transplantation
• Donor factors- -Extreme of age
-Presence of pre-existing disease
-Hemodynamic and metabolic instability
• Procurement related factors-
-Warm ischemic time
- Type of preservation solution
- Cold ischemic time
• Recipient factors- Technical surgical factors
- Hemodynamic and metabolic stability
-Immunological factors –sensitisation status
- Drug therapy impairing function of organ

18. Outcome after transplantation
• Transplant improves the quality and duration of life in
most of recipients
• Transplant outcome has improved progressivel due to
better immunotherapy,organ preservat ion,
chemoprophylaxis and technical advances
• Graft survival after kidney,heart and liver trans plant is
around 90% at 1 yr and 70-80% at 5yrs
• Results of lung and small intestine transplant are less
impressive
• Chronic rejection is most common cause of graft
failure after all types of solid organ transplant
• Recurrance of original disease may lead to graft failure
• Death from CV disease with functioning transplanted
organ is common

19. Heart Transplant
• 1967-1st human heart transplant by Dr
Christiaan Barnard in Cape Town South Africa
(based on labortory work of Shumway & Lower)
• Indications - End stage cardiac disease where
all conventional therapy has failed -
a. Idiopathic cardiomyopathy
b. Ischemic heart disease ( diffuse smal vessels)
c uncorrectabe congenial heart disease
d.Myocarditis
• Pre requisite- Age – Below age of 65 yrs ,PVR
should be in normal range , Other organ systems
( kidney,liver) are not permanently damaged

20. Dr Christian Barnard 1st heart transplant patient

21. Dr Barnard with ICU nurses Dr Barnard briefing media

22. Dr Norman Shumway Transplanted Heart

23. Contraindications to transplantation
• Absolute-
Active infection ( or HIV positve ) -
Irreversible PAH -Malignancy -
Presence of another serious disease
• Relative contraindications-
Age > 60yrs -Active D U
- Significant raised PVR
-Drug or Alcohol abuse
- Psychiateric illness
- Low creatinine clearance

24. Surgical technique
• Median sternotomy- Systemic heparinisation
and pt is placed on CP Bypass,cooled to 26 C
-Aorta cross clamped and recipient heart excised
at mid atrial level
- Donor heart is removed from ice, left atrium
opened by incisions in post. wall between
orifices of pulm. Veins to make atrial cuff
- Left and then right atrial anastomoses done
and Pulm artery and Aorta anastomosed to
donor vessels. Pt rewarmed and weaned off
from CPB.

25. Heart transplant technique

26. Prognosis
Graft survival of transplanted Heart
• 1 year : 88.0% (males), 86.2% (females)
• 3 years: 79.3% (males), 77.2% (females)
• 5 years: 73.2% (males), 69.0% (females)
Graft survival of Heart lung and Lung transplant
1 yr survival 75%
5 yrs survival 40%

27. Heart –lung transplant
• 1981 –1st successful combined heart lung
transplan by Bruce Ritz
• It is done in pts with Pulm.Vascular disease due to
Eisenmenger Synderome or due to acquired heart
disease
• Through midsternotomy diseased lungs and heart
are excised preserving phrenic, vagus and
recurrent laryngeal nerves.Donor heart lungs
block placed and end to end tracheal anastomo
sis is done and RA and aortic anastomoses are
done as for cardiac ransplantation

28. Bruce Ritz Ist heart lung transplant

29. Lung transplant
• James Hardy USA did 1st lung transplant in 1964, Joel Cooper USA
popularised it
• Single and double lung transplant are effetive treatment of chronic
lung disease with declin ing PFT limiting life expectancy
• Indications- Single lung transplant Pulmonary fibrosis
Double lung transplantt
b-Cystic fibrosis c-B/L bronchiectasis
• Single lung transplant is done through PLT and B/L lung transplant is
done through midsternoto my or B/L ant. thoracotomy.
• Incidence of post op airway anastomosis dehiscence used to be
common is now less than 5%due to better organ pre servation and
better surgical techniques.Late airway stenosis at bronchial anasto
mosis due to ischemia ois ccurs in about 10% and is treated by
dilatation
• Prognosis - 1 and 5 yrs survival of heart transplant is 85% and 70%
Results of heart lung and lung transplant is 75% and 40% at 1 and
5yrs

30. James Hardy Joel D Cooper

32. Future developments
• Better immunosuppressive drugs
• Xenotransplantation
• Stem cell engineering
• Non invasive biomarkers for monitoring
rejection
• Methods to induce donor specific immunolo-gical
tolerance

33. Thank You