trapianto e alternative

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IL TRAPIANTO DI CUORE NELLA STORIA
1905Carrel e Guthrie HTX eterotopico di cuore
nel cane 1960Shumway descrizione tecnica di HTX
su uomo 1967Barnard primo HTX ortotopico
umano 1969Cooley primo cuore-polmone 1980Standf
ord University ciclosporina 1984Yacoub primo
neonato 1985Gallucci primo trapianto di cuore
in ITALIA
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IL TRAPIANTO DI CUORE RAPPRESENTA IL TRATTAMENTO
ELETTIVO PER LA MAGGIORANZA DELLE CARDIOPATIE
TERMINALI. (NORMAN SHUMWAY 1998) OGNI ANNO VI
SONO CIRCA 40.000 NUOVI CANDIDATI AL
TRAPIANTO OGNI ANNO VENGONO EFFETTUATI CIRCA
3.500 NUOVI TRAPIANTI
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INDICAZIONI E CONTROINDICAZIONI - RICEVENTE
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VALUTAZIONE DEL POTENZIALE DONATORE CARDIACO

• ANAMNESI ACCURATA
• MALATTIE CARDIOVASCOLARI, E SISTEMICHE
• STORIA SOCIALE
• IPOTENSIONI E/O ARRESTI CARDIACI
• VALUTAZIONE STRUMENTALE
• ECOCUORE
• DOSAGGIO INOTROPI E DURATA
• ECG
• RX TORACE
• CK/MB , TROPONINA T/I
• VALUTAZIONE CLINICA
• ESAME DIRETTO DEL CUORE CORONARIE E CATETERISMO
  DX

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TRAPIANTO DI CUORE IL DONATORE INDICAZIONI E
CONTROINDICAZIONI RELATIVE
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Surgical technique for orthotopic cardiac
transplantation Biatrial technique
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Surgical technique for orthotopic cardiac
transplantation Bicaval technique
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The heterotopic technique (the original
transplantation performed by Dr. Christian
Barnard in 1967)
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IL RIGETTO ACUTO E CRONICO CODIZIONANO LA
SOPRAVVIVENZA DEL TRAPIANTO
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RIGETTO ACUTO
REAZIONE DEL SISTEMA IMMUNITARIO NEI CONFRONTI
DEGLI ANTIGENI DEL TRAPIANTO RICONOSCIUTI COME
NON-SELF DAL MHC (HLA).
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Histologic grading of allograft rejection
Histologic grading of allograft rejection. In
order to monitor rejection, periodic
endomyocardial biopsies are performed. A, The
percutaneous technique of endomyocardial biopsy
using the Caves bioptome. The bioptome is
inserted through the internal jugular vein to the
right ventricular portion of the interventricular
septum under fluoroscopy. Four to six specimens
containing at least 50 myocytes are required for
90 to 95 confidence in the interpretation.
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ISHLT ENDOMYOCARDIAL GRADING SYSTEM

Histologic grading of allograft rejection
Histologic grading of allograft rejection. In
order to monitor rejection, periodic
endomyocardial biopsies are performed. The
standardization of histologic biopsy grading
according to the International Society for Heart
Transplantation (ISHLT).
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Representative endomyocardial biopsies
Hematoxylin and eosin staining of representative
endomyocardial biopsies at a magnification of 100
x showing grade 1B rejection with focal
lymphocytic infiltrate without evidence of
myocardial necrosis (A), grade 3A rejection
demonstrating more intensive lymphocytic
infiltration and myocyte necrosis (B), and grade
4 allograft rejection with extensive lymphocyte
infiltration, myocyte necrosis, and hemorrhage
(C).
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TERAPIA IMMUNOSOPPRESSIVA

• TRIPLICE STANDARD CICLOSPORINA A 5 MG/KG DIE
  OS AZIOTOPRINA 2 MG/KG DIE OS
  PREDNISONE 0,2 MG/KG DIE OS
• TERAPIA RIGETTO ACUTO
• 1A NESSUN TRATTAMENTO
• 1B NESSUN TRATTAMENTO OD INCREMENTO CORTISONE
• 2 EVENTUALE CICLO CORTISONE
• 3A METILPREDNISOLONE
• 3B METILPREDNISOLONE (eventualmente uso di sieri
  ALG)
• 4 ALG 15 mg/kg/die X 7 gg (eventuale uso
  OKT3)

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RIGETTO CRONICO

• UN DANNO PROLUNGATO NEL TEMPO DELLE CELLULE
  ENDOTELIALI E PROBABILMENTE ALLA BASE DELLE
  LESIONI ATS CHE DOPO 5 ANNI IL 40-50 DEI
  PAZIENTI TRAPIANTATI PRESENTA.
• QUESTE LESIONI SI RISCONTRANO SENZA RELAZIONE CON
  LA PATOLOGIA INIZIALE DEL RICEVENTE E VENGONO
  CONSIDERATE COME MANIFESTAZIONI DI RIGETTO
  CRONICO.

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DIAGNOSI RIGETTO CRONICO

• ECG/ECO/SCINTIGRAFIA
• TARDIVI
• CORONAROGRAFIA ANNUALE
• DIAGNOSI
• ECOGRAFIA INTRA CORONARICA
• FUTURE TREND

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ETIOPATOGENESI RIGETTO CRONICO A) DANNO
INTIMALE DI ORIGINE IMMUNOLOGICA B) AGGREGAZIONE
PIASTRINICA C) PROLIFERAZIONE INTIMALE
D) LESIONE ATS
Mismatch HLA
Immunosoppres.
CMV
Eta'
N episodi acuti
Miocardioprotezione
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Transplantation coronary allograft disease
The major cause of late death after cardiac
transplantation is the development of TCAD, a
unique accelerated form of coronary artery
disease. By 1 year posttransplant, about 30 of
patients demonstrate some TCAD, and the incidence
and severity continue to increase with time. The
pathogenesis of TCAD is thought to begin with
immunologic and nonimmunologic injury to the
arterial endothelium, with resultant loss of
endothelial integrity. Microthrombi, cellular
proliferation, and plasma lipids accumulate at
the site of the injured intima. A, This leads to
further cellular proliferation and finally
profound myointimal hyperplasia leading to
diffuse coronary artery lumen narrowing. B,
Selective left coronary angiography from a
patient with severe TCAD, which shows diffuse
tapering of the left anterior descending and
circumflex arteries as well as pruning of all the
secondary vessels. Risk factors Immunologic
mechanisms resulting in endothelial injury
include both cellular and humoral factors and
Nonimmunologic (Recipient age and gender, donor
age and gender, obesity, hyperlipidemia, and
donor ischemic time the presence of active
cytomegalovirus infection. Given the diffuse,
concentric nature of this disease, percutaneous
transluminal coronary angioplasty and coronary
artery bypass grafting are not useful strategies
for management. Unfortunately, patients with TCAD
have a fivefold greater risk of cardiac events
such as myocardial infarction, severe refractory
heart failure, and sudden death. Presently,
retransplantation is the only treatment for
severe TCAD however, survival after repeat
transplantation is significantly reduced.
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TERAPIA RIGETTO CRONICO

• TERAPIA IMMUNOSOPPRESSIVA (NUOVI AGENTI,CYA ALTE
  DOSI)
• FATTORI RISCHIO ATS
• ANTIAGGREGANTI
• LESIONI TIPO A (ATS CLASSICA)gtgtgtCABG
• LESIONI TIPO B (PLACCA LOCALIZZATA)gtgtgtPTCA/CABG
• LESIONI TIPO C (RIDUZIONE UNIFORME ED
  ESTESA)gtgtgtHTX/REDO

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ADULT HEART TRANSPLANTATION ACTUARIAL SURVIVAL
Survival ()
All comparisons with 1980-1987 are significant at
p lt 0.0001
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FUNCTIONAL STATUS
Heart (April 1994-Dec. 2000)
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HEART TRANSPLANTS CAUSE OF DEATH (1982-2000)
Cause of Death ()
Timing of Death
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HEART TRANSPLANTATION
Percent of Donors by Age
Numbers may be low due to incomplete reporting.
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Legge 91/99
La legge 91/99 disciplina il prelievo ed il
trapianto di organi e tessuti da soggetto di cui
sia stata accertata la morte cerebrale (Legge n
578/93).
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THE PROBLEM OF ORGAN STORAGE
HUMAN ORGANS FOR TRANSPLANTATION ARE
INSUFFICIENT, AND FOR EVERY ORGAN TRANSPLANT
CARRIED OUT, THERE IS A LACK OF DONORS FOR AS
MANY AS 5-10 MORE
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ATTUALMENTE CIRCA IL 50 DEI PAZIENTI IN LISTA DI
ATTESA PER TRAPIANTO DI CUORE MUORE PRIMA CHE SIA
REPERITO UN ORGANO
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Possibili alternative al trapianto
NUOVE STRATEGIE FARMACOLOGICHE
FUTURO
CABG IN END-STAGE
CARDIOMIOPLASTICA
BATISTA
XENOTRAPIANTO
CUORE ARTIFICIALE
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The Abiomed
Pulsatile extra-corporeal assist device that can
provide univentricular or biventricular support.
Cannulae are placed either in the right or left
atria, and blood flows into the two-chamber
device. An atrial filling chamber connects a
trileaflet valve to a ventricular pumping
chamber. Each chamber consists of a 100-mL,
smooth-surfaced, polyurethane bladder. The atrial
chamber fills passively by gravity. The
ventricular chamber fills and empties through
pneumatic compression of the bladder by a
console. Blood flows to an arterial Dacron graft
cannula that inserts into the pulmonary artery or
the ascending aorta.
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Cuore Artificiale Impiantabile
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The Novacor device
The Thermocardiac device
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Percutaneous VAD (pVAD)

• The device (TandemHeart pVAD) is designed to
  allow rapid deployment through femoral access to
  the heart and circulatory system.
• Delivers up to 6 liters per minute flow
• Lightweight - 280 grams
• Compact - accommodates a wide range of patients
• Only 7ml priming volume

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• Chest x-ray on admission showing cardiomegaly
  and severe pulmonary congestion.

On day 5 with theTandemHeart the heart size is
reduced, and there is no pulmonary congestion.
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LO XENOTRAPIANTO

• E IL TRAPIANTO DORGANI FRA SPECIE DIFFERENTI
  (p.e. UOMO - MAIALE)
• DISPONIBILITA ILLIMITATA DI ORGANI PER IL
  TRAPIANTO
• POSSIBILITA DI TRASMISSIONE ALLUOMO DI MALATTIE
  INFETTIVE (PERV)

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Transgenic Animals
A Transgenic animal is one containing recombinant
DNA molecules (transgenes) in its genome that
were introduced by intentional human intervention
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XENOTRANSPLANTATION SOURCE OF ORGANS
THE PIG IS CURRENTLY CONSIDERED THE MOST LIKELY
SOURCE OF ORGANS FOR HUMAN XENOTRANSPLANTATION
BECAUSE OF ITS EASY BREEDING, COMPATIBLE SIZE
ORGANS AND THE APTITUDE TO GENETIC MANIPULATION.
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PIG TO MAN XENOTRANSPLANTATION

• EASY BREEDING
• SHORT GENERATION TIME
• ORGANS OF COMPATIBLE SIZE
• PRODUCTION OF SPF COLONIES
• APTITUDE TO GENETIC MANIPULATION
• LOW EMOTIONAL IMPACT

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XENOTRANSPLANTATION RISK AND BENEFITS

• POSSIBILITY OF NEW DISEASE ENTERING THE HUMAN
  POPULATION
• SHORTAGE OF HUMAN DONOR ORGANS FOR
  ALLOTRANSPLANTATION PROMISES A GREAT BENEFIT TO
  PATIENTS
• POTENTIAL MEDICAL BENEFITS COULD OUTWEIGH
  INFECTIOUS DISEASE RISKS AND ANY DANGERS
  REPRESENT MENEGEABLE RISK
• (Nature 1998)

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IL RIGETTO IPERACUTO

• MEDIATO DAL COMPLEMENTO, DISTRUGGE I VASI
  SANGUIGNI DELLORGANO TRAPIANTATO IN POCHI MINUTI
• E POSSIBILE EVITARE TALE RIGETTO TRAMITE
  LUTILIZZO DI ANIMALI GENETICAMENTE MODIFICATI