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IL TRAPIANTO DI CUORE NELLA STORIA

IL TRAPIANTO DI CUORE NELLA STORIA. 1905 :Carrel e Guthrie: HTX eterotopico di cuore nel cane 1960 :Shumway: descrizione tecnica di HTX su uomo 1967 :Barnard: primo HTX ortotopico umano 1969 :Cooley: primo cuore-polmone 1980 :Standford University: ciclosporina 1984 :Yacoub: primo neonato

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IL TRAPIANTO DI CUORE NELLA STORIA

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  1. IL TRAPIANTO DI CUORE NELLA STORIA 1905:Carrel e Guthrie: HTX eterotopico di cuore nel cane 1960:Shumway: descrizione tecnica di HTX su uomo 1967:Barnard: primo HTX ortotopico umano 1969:Cooley: primo cuore-polmone 1980:Standford University: ciclosporina 1984:Yacoub: primo neonato 1985:Gallucci: primo trapianto di cuore in ITALIA

  2. Dr. Norman E. Shumway In 1968 Dr. Norman Shumway performed the first heart transplant in the United States.

  3. 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

  4. INDICAZIONI E CONTROINDICAZIONI - RICEVENTE

  5. 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

  6. NORMALE ECOCARDIOGRAMMA MINIME ANOMALIE NORMALE ECG ANOMALIE ASPECIFICHE NO ENZIMI mb <50 (?) NO ARRESTI DURATA<30’ (?) NO INOTROPI > 15 g/kg/min (?) NO SEPSI INFEZIONI POLMONARI ETA’ < 50aa (CORONAROGRAFIA ?) TRAPIANTO DI CUORE: IL DONATORE INDICAZIONI E CONTROINDICAZIONI RELATIVE

  7. Surgical technique for orthotopic cardiac transplantation: Biatrial technique

  8. Surgical technique for orthotopic cardiac transplantation: Bicaval technique

  9. The heterotopic technique (the original transplantation performed by Dr. Christian Barnard in 1967)

  10. IL RIGETTO ACUTO E CRONICO CODIZIONANO LA SOPRAVVIVENZA DEL TRAPIANTO

  11. RIGETTO ACUTO REAZIONE DEL SISTEMA IMMUNITARIO NEI CONFRONTI DEGLI ANTIGENI DEL TRAPIANTO RICONOSCIUTI COME “NON-SELF” DAL MHC (HLA).

  12. 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.

  13. GRADE HISTOLOGIC DESCRIPTION 0 No rejection 1A Focal perivascular or interstitial infiltrate without necrosis 1B Diffuse but sparse infiltrate without necrosis 2 One focus of aggressive infiltration or focal myocyte damage 3A Multifocal aggressive infiltrates or myocyte damage 3B Diffuse inflammatory process with necrosis 4 Diffuse aggressive polymorphous infiltrate with necrosis ±edema, ±hemorrhage, ±vasculitis 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).

  14. 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).

  15. 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)

  16. 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.

  17. DIAGNOSI RIGETTO CRONICO • ECG/ECO/SCINTIGRAFIA • TARDIVI • CORONAROGRAFIA ANNUALE • DIAGNOSI • ECOGRAFIA INTRA CORONARICA • FUTURE TREND

  18. 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

  19. 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.

  20. TERAPIA RIGETTO CRONICO • TERAPIA IMMUNOSOPPRESSIVA(NUOVI AGENTI,CYA ALTE DOSI) • FATTORI RISCHIO ATS • ANTIAGGREGANTI • LESIONI TIPO A(ATS CLASSICA)>>>CABG • LESIONI TIPO B(PLACCA LOCALIZZATA)>>>PTCA/CABG • LESIONI TIPO C(RIDUZIONE UNIFORME ED ESTESA)>>>HTX/REDO

  21. ADULT HEART TRANSPLANTATIONACTUARIAL SURVIVAL Survival (%) All comparisons with 1980-1987 are significant at p < 0.0001

  22. FUNCTIONAL STATUS Heart (April 1994-Dec. 2000)

  23. HEART TRANSPLANTS: CAUSE OF DEATH(1982-2000) Cause of Death (%) Timing of Death

  24. % donors 50-55 % donors 50+ 12% 9% Number of Transplants * 6% 3% * HEART TRANSPLANTATION Percent of Donors by Age * Numbers may be low due to incomplete reporting.

  25. 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).

  26. 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

  27. ATTUALMENTE CIRCA IL 50% DEI PAZIENTI IN LISTA DI ATTESA PER TRAPIANTO DI CUORE MUORE PRIMA CHE SIA REPERITO UN ORGANO

  28. Possibili alternative al trapianto NUOVE STRATEGIE FARMACOLOGICHE FUTURO CABG IN “END-STAGE” CARDIOMIOPLASTICA BATISTA XENOTRAPIANTO CUORE ARTIFICIALE

  29. 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.

  30. Cuore Artificiale Impiantabile

  31. The Novacor device The Thermocardiac device

  32. The Jarvic 2000

  33. PercutaneousVAD (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

  34. 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.

  35. LO XENOTRAPIANTO • E’ IL TRAPIANTO D’ORGANI FRA SPECIE DIFFERENTI (p.e. UOMO - MAIALE) • DISPONIBILITA’ ILLIMITATA DI ORGANI PER IL TRAPIANTO • POSSIBILITA’ DI TRASMISSIONE ALL’UOMO DI MALATTIE INFETTIVE (PERV)

  36. Transgenic Animals • A Transgenic animal is one containing recombinant DNA molecules (transgenes) in its genome that were introduced by intentional human intervention

  37. 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.

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

  39. 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)

  40. IL RIGETTO IPERACUTO • MEDIATO DAL COMPLEMENTO, DISTRUGGE I VASI SANGUIGNI DELL’ORGANO TRAPIANTATO IN POCHI MINUTI • E’ POSSIBILE EVITARE TALE RIGETTO TRAMITE L’UTILIZZO DI ANIMALI GENETICAMENTE MODIFICATI

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