Cardiac transplantation





Pearls





  • Most pediatric transplantations are performed for cardiomyopathy or congenital heart disease not amenable to correction or palliation.



  • Individuals may have a good quality of life following heart transplantation but are likely destined for a repeat transplant.



  • ABO-incompatible heart transplantation is possible in young children and infants with outcomes comparable to ABO-compatible transplantation.



  • Diastolic dysfunction may persist for several months following transplantation.



  • Right heart support is important after postcardiac transplantation.



  • Immunosuppression should start immediately following transplantation.



  • The high-risk period for acute allograft rejection is in the first month after transplantation.



  • Complications of immunosuppression are infection, acute renal failure, malignancy, and hyperglycemia.



Background


It has now been nearly 4 decades since the first successful pediatric heart transplantation was performed at Stanford University. Approximately 700 pediatric heart transplantations are now performed annually worldwide, with over 400 of those performed in the United States. A quarter of these transplantations are performed in children younger than 1 year. The remainder are split fairly evenly between children 1 to 10 years of age and adolescents younger than 18 years. The majority of infant transplantations are performed owing to congenital heart disease not amenable to correction or palliation, while the majority of adolescent transplantations are for cardiomyopathy.


With improvements in immunosuppression and medical care, the overall transplant survival at 1 year has improved to over 90%, and we now expect 5-year survival to exceed 80%. From the newest survival data (International Society for Heart and Lung Transplantation 2018 Report ), the time at which 50% of recipients remain alive is 13.3 years for teenagers and 22.3 years for infants. Late death after transplantation is the result of posttransplant coronary vasculopathy, malignancy, or rejection due to nonadherence to immunosuppression regimens. , Rehospitalization after the first year is rare, and quality of life has been excellent.


Advances in our understanding of the immune system and improvements in critical care management of both donor and recipient patients have resulted in an increased survival benefit. Although overall perioperative mortality has greatly improved over the past 25 years, increased risk of mortality has been seen in patients with the diagnosis of congenital heart disease—especially infants—and those undergoing retransplant. One cause of early mortality is failure of the allograft to perform adequately, also known as primary graft dysfunction. Reasons for primary graft dysfunction include myocardial injury from inadequate organ preservation or long ischemic times, and elevated pulmonary vascular resistance (PVR) with pulmonary hypertension causing right ventricular failure. Acute allograft rejection is an exceedingly rare event immediately after transplantation.


The physiology of the transplanted heart as well as preoperative and perioperative critical care play important roles in the successful transplantation of critically ill children with limited other options. This chapter reviews critical care management of the pediatric patient undergoing heart transplantation.


Indications for transplant


In 1995, the International Society for Heart and Lung Transplantation identified the following reasons as indications for pediatric heart transplantation :




  • Need for ongoing intravenous (IV) inotropic or mechanical circulatory support



  • Complex congenital heart disease not amenable to conventional surgical repair or palliation, or for which the surgical procedure carried a higher risk of mortality than transplantation



  • Progressive deterioration of ventricular function or functional status despite optimal medical care with digitalis, diuretics, angiotensin-converting enzyme inhibitors, β-blockers, and/or other oral heart failure therapies



  • Malignant arrhythmia or survival of cardiac arrest unresponsive to medical treatment, catheter ablation, or an automatic implantable defibrillator



  • Progressive pulmonary hypertension that could preclude cardiac transplantation at a later date



  • Growth failure secondary to severe congestive heart failure unresponsive to conventional medical treatment



  • Unacceptable poor quality of life secondary to heart failure



Transplant evaluation


Once a child is seriously considered for a heart transplant, an extensive evaluation is required to determine suitability for transplantation. This evaluation includes laboratory and imaging studies to elucidate the degree of heart failure and confirm that no further medical or surgical options are available for treatment as well as to investigate any potential contraindications to transplantation. Major contraindications to pediatric heart transplantation include:




  • Presence of any noncardiac condition that would significantly shorten life expectancy beyond what would otherwise be expected with cardiac transplantation. Examples include severe neuromuscular disease, active neoplasm, genetic disorders with poor prognosis, and severe immunodeficiency.



  • Presence of any noncardiac condition that may affect the transplanted heart and therefore also shorten life expectancy. Examples include significantly elevated and nonreactive PVR, mitochondrial disease, active infection, and morbid obesity (body mass index > 35).



  • Social factors—including unstable/unreliable caregiver system, history of recurrent medical noncompliance, and history of or current recreational drug use.



In addition to these factors, relative contraindications include elevated but reactive PVR, history of malignancy, stroke, elevated panel reactive antibody (PRA), significant hepatic dysfunction, and/or significant renal insufficiency. In these cases, multiorgan transplantation might be considered.


A typical transplant evaluation consists of laboratory and imaging studies, pulmonary function testing and exercise testing, cardiac catheterization, and various consultations. These consultations include social work, financial, nutrition, psychology, and indicated subspecialty consults. Box 37.1 summarizes this evaluation. The goal of laboratory evaluation, in addition to blood typing and PRA profile, is to identify infectious risk factors and overall end-organ and metabolic health. Imaging studies—including magnetic resonance imaging (MRI)/magnetic resonance angiography and/or computed tomography (CT) angiography—may assist surgical teams in planning the transplant procedure as well as assessing suitability of potential donors, particularly in children with complex congenital heart disease. A cardiac catheterization is generally indicated to determine cardiac indices as well as PVR and reactivity.



• BOX 37.1

Heart Transplant Evaluation





  • Laboratory Testing




    • Chemistry




      • Complete metabolic profile with electrolytes, hepatic panel, uric acid, lactate dehydrogenase, and blood urea nitrogen and creatinine



      • Fasting lipid profile



      • Thyroid function testing, other metabolic evaluation as indicated



      • Urinalysis




    • Hematology




      • Complete blood count with differential



      • Coagulation panel



      • Blood typing and blood group antibody screening




    • Immunology




      • Panel of reactive antibody




    • Infectious disease




      • Viral testing for cytomegalovirus, Epstein-Barr virus, herpes, human immunodeficiency virus, human T- cell leukemia virus, varicella, toxoplasmosis, and other studies as indicated



      • Hepatitis panel




    • Cardiac catheterization and other imaging as needed (magnetic resonance imaging, computed tomography)



    • Exercise testing



    • Psychosocial evaluation



    • Financial consultation



    • Other subspecialty consultations as required





Panel reactive antibody


The PRA is an immunologic test routinely performed to determine a recipient’s antibody response to human leukocyte antigens, a protein that coats human cells and is unique to each individual. Exposure to nonself human proteins results in production of antihuman leukocyte antigen (anti-HLA) antibodies, a phenomenon known as sensitization. Sensitization to HLA can occur with administration of blood products, implantation of nonself human tissue into the body, use of a ventricular assist device, or pregnancy. The former two often occur in children undergoing palliative or corrective surgery for congenital heart disease. Anti-HLA antibodies may also develop spontaneously.


HLAs are divided into two classes, class I and class II, and are specified by a letter (A, B, C, DR, DQ) and number code (e.g., A2, B8, C6) based on the molecular structure. The PRA test is performed by exposing a potential recipient’s serum to the lymphocytes of a panel of about 100 blood donors. Results are reported in percentage of positive reactions within the panel from 0% to 100%. Thus, if a recipient reacts to 50 of 100 samples, the PRA is 50%. This test is reported for class I and class II antigens separately. Current testing is predominately performed with Luminex beads, which allows for HLA specificities to be reported. In other words, a list of antigen codes producing a positive antibody reaction can be generated. These would be the undesirable antigens in a donor that could stimulate production of undesirable donor-specific antibodies (DSAs) and give a positive crossmatch. Knowing these antigens allows a virtual crossmatch to be performed comparing the donor HLAs with the list of anti-HLA antibodies of the recipient. A positive virtual crossmatch is likely to give a positive retrospective crossmatch if that heart were to be implanted.


The presence of DSAs is associated with antibody-mediated rejection and can reduce the longevity of the cardiac allograft. A PRA of more than 10% has historically been associated with decreased posttransplant 1-year graft survival. Strategies exist to reduce anti-HLA antibodies pretransplant, although variable in success, as well as strategies posttransplant to reduce the impact of DSAs, predominately with plasmapheresis. PRA in patients with repaired or palliated congenital heart disease can often be over 80%.


Transplant listing


Once all the components of the evaluation are complete, candidates are presented at the respective center’s listing conference. Key members of the listing conference include the transplant medical director, medical transplant team and transplant coordinators, transplant surgeons, social workers, and the center’s financial counselors. Each candidate is presented and all medical data are reviewed, along with recommendations from all consultants. At that time, a determination is made as to whether or not it is appropriate to list a candidate for transplant; if a candidate is found to be unsuitable, the team should determine what steps, if any, could be taken to make the candidate more suitable. If a candidate is suitable for listing, as of 2020, there are currently three active listing statuses in which to place candidates and one inactive status. Box 37.2 summarizes the United Network for Organ Sharing (UNOS) status allocation for pediatric heart transplantation.



• BOX 37.2

United Network for Organ Sharing Allocation Status Criteria


Status 1A


Candidate must meet one of the following:




  • Significant congenital heart disease diagnosis requiring infusion of multiple intravenous inotropes or a high dose of a single intravenous inotrope and admitted to the hospital that registered the candidate



  • Ductal-dependent pulmonary or systemic circulation with ductal dependency maintained by prostaglandin E infusion or stent and admitted to the transplant hospital that registered the candidate



  • Continuous mechanical ventilation and admitted to the hospital that registered the candidate



  • Requires assistance with a mechanical circulatory support device (e.g., extracorporeal membrane oxygenation, left ventricular assist device). Does not require hospitalization.



  • Requires assistance with an intraaortic balloon pump and admitted to the hospital that registered the candidate



  • Patient does not meet any of these specified criteria but has a suspected life expectancy of <14 days without heart transplantation (e.g., refractory arrhythmia)



Status 1B


Candidate must meet one of the following:




  • Continuous infusion of one or more inotropes and does not qualify for pediatric status 1A. Does not require hospitalization.



  • Less than 1 year of age at the time of initial listing and has restrictive or hypertrophic cardiomyopathy



Status 2





  • Individuals not meeting pediatric status 1A or 1B criteria



Status 7





  • Listed but inactive. May be too well or too ill for transplant, or may have other patient/center-specific issues precluding transplant




Wait list times vary from region to region for each listing status and vary greatly by recipient age. When an organ offer is received, the medical and surgical members of the transplant team review the offer for suitability for the intended recipient. Several factors require careful consideration, including size match, antibody profile, infectious profile, and quality of the donor heart, among others.


Management of the potential heart transplant recipient


The pretransplant management of the critically ill patient with end-stage myocardial dysfunction can determine the outcome of that patient after thoracic transplant. In general, the more comorbidities a patient has pretransplant, the longer and more complicated their posttransplant clinical course may be. Many pediatric heart transplant candidates can be managed in the outpatient setting on an oral heart failure regimen with close follow-up. These patients may be on a combination of angiotensin-converting enzyme inhibitors, β-blockers, potassium-sparing agents (i.e., spironolactone), and diuretics. However, once a patient becomes symptomatic at rest, inpatient heart failure treatment is indicated. The principles of inotropic support, preservation of end-organ function, and attention to issues of nutrition and infection are the same as those for all other critically ill patients in the pediatric intensive care unit (ICU). In addition, careful attention must be paid to the presence and management of dysrhythmias.


Critically ill children with myopathic ventricular dysfunction severe enough for them to be in the ICU generally require inotropic support. These agents increase contractility through a common pathway of increasing intracellular levels of cyclic adenylate monophosphate (cAMP). Increased cytoplasmic levels of cAMP cause increased release of calcium from the sarcoplasmic reticulum and increase contractile force generation. Increases in cAMP occur either by β-adrenergic–mediated stimulation (increased production) or phosphodiesterase 3 (PDE3) inhibition (decreased degradation).


Milrinone has been well studied in the pediatric population and proven to be well tolerated. IV administration of milrinone increases cardiac output and reduces cardiac filling pressures and PVR and systemic vascular resistance (SVR) with minimal effect on heart rate. , The increase in cardiac output is primarily due to its effect on PVR and SVR rather than a direct inotropic effect on the myocardium. Milrinone is generally initiated at doses of 0.25 μg/kg per minute and may be increased to 1 μg/kg per minute without significant adverse effects. This drug is primarily excreted in the urine; thus, serum concentrations can increase in the presence of renal insufficiency and dose adjustments should be made. Although atrial and ventricular ectopy are less common with milrinone than with other inotropes, ventricular arrhythmias can occur with the initiation of milrinone therapy, especially in the presence of renal dysfunction. Milrinone has a long half-life and should be used cautiously in patients with hypotension. The addition of low-dose epinephrine (0.01–0.05 μg/kg per minute), dopamine (3–5 μg/kg per minute), or dobutamine (2.5–5 μg/kg per minute) can help stabilize the critically ill child who is not responding adequately to milrinone therapy alone or who needs blood pressure augmentation prior to initiating milrinone therapy. Tachyphylaxis is unusual with milrinone. Milrinone effects may persist for several hours or days after discontinuation of a prolonged infusion.


It is important to note that wait list times may be long even for the sickest children at the highest status awaiting a transplant, sometimes several months. In fact, pediatric wait list mortality overall is about 15% and can be significantly higher in select populations, such as those with congenital heart disease. Most patients waiting for heart transplantation who are on inotropic support do not remain hemodynamically stable indefinitely. Progressive end-organ dysfunction eventually ensues, requiring escalation of support that includes multiple inotropic agents in addition to respiratory and circulatory support. Mechanical ventilatory support may be needed to manage respiratory failure, control the effects of pulmonary edema, and reduce metabolic demand. Use of mechanical ventilation is a risk factor for wait list mortality and reduced survival following pediatric heart transplantation. It is currently a criterion for 1A status.


Mechanical circulatory support has become an important addition to the treatment armamentarium for the infant or child with decompensated heart failure and low cardiac output unresponsive to pharmacologic maneuvers. Options include extracorporeal membrane oxygenation (ECMO), intraaortic balloon, and left ventricular and right ventricular assist devices. Experience with ECMO as a bridge to heart transplantation has been reported by several pediatric transplant centers. , ECMO support generally can be used for 2 to 3 weeks without major complications from bleeding or infection, extending the window for donor organ availability. However, ECMO use increases the risk of wait list mortality and is associated with reduced posttransplant survival. ,


Isolated ventricular support devices, such as the Thoratec, Berlin Heart, HeartWare, and Heartmate pumps, are also available for use in some children. However, the Berlin Heart EXCOR is the only device approved by the US Food and Drug Administration for use in children. Placement of a device should be considered for signs and symptoms of persistent heart failure refractory to inotropic support and/or with concern for multiorgan dysfunction. Placement of a device in a patient with multisystem organ failure usually results in a poor outcome. We propose that these devices be placed early, before end-organ dysfunction. Doing so enables rehabilitation of the patient, who then becomes a more optimal candidate for organ transplantation. The use of a ventricular assist device has been associated with improved wait list mortality and posttransplant outcomes. , ,


Anticoagulation


All patients with severe myocardial dysfunction are at risk for complications of systemic and pulmonary emboli. While there are no established guidelines for thrombosis prophylaxis in pediatric patients, most centers consider antiplatelet therapy with aspirin and/or anticoagulation with heparin or warfarin. Low-molecular-weight heparin is generally not used, as it cannot be easily reversed in a patient who must go to the operating room urgently once a donor heart has been identified.


ABO-incompatible listing and transplantation


At present, it is possible to perform an ABO-incompatible (ABOi) heart transplantation without risk of hyperacute rejection if performed prior to maturation of the immune system and development of isohemagglutinins, generally under 12 months of age and possibly under 24 months. ABOi posttransplant outcomes have been shown not to be statistically different from ABO-compatible transplantation outcomes, and there has also been some improvement in wait list outcomes. The UNOS allows listing of patients 1 to 2 years of age as eligible for ABOi transplantation with an A or B isohemagglutinin titer less than 1:16 and no limit on titer for those younger than 1 year. Most centers now have protocols regarding pre- and posttransplant care for individuals listed as eligible for and undergoing an ABOi transplantation. Predominately, the management centers on avoiding sensitization events related to administration of blood products and strict adherence to blood-typing protocol when blood products are needed.


Critical care management of the orthotopic heart transplant recipient


Intraoperative considerations


Posttransplant cardiac function is affected by multiple factors, such as recipient pretransplant characteristics, donor characteristics and management, preservation techniques, and total ischemic time of the donor heart. Total ischemic time is defined as the total time starting from placement of the cross-clamp on the donor aorta to release of the recipient cross-clamp and is a major factor in early posttransplant cardiac function and transplant outcomes. Total ischemic times of less than 4 hours typically are associated with better graft function and posttransplant outcomes. Because of this, a great deal of planning goes into keeping ischemic time as low as possible. This includes planning for repeat sternotomies or performing any reconstruction that needs to be done prior to donor heart implantation, considering the logistics and travel times to donor site, and using implant techniques that reduce ischemic time.


Techniques of implantation have not changed significantly since the original description. , Although modifications may be necessary in transplantation for complex congenital heart disease patients, heart transplantation can be accomplished in virtually any congenital heart anomaly because the anatomic position of the aorta, pulmonary arteries, and left atrium are in a relatively constant position near the midline. Regardless of malposition or positional relationships of the great arteries, the aorta of the recipient can be mobilized to make anastomosis with the donor aorta possible. The left atrium is a midline structure; even when anomalies of pulmonary venous return exist, pulmonary veins usually approach the midline and can be incorporated into the repair. However, aortic root size mismatch can cause technical difficulty. Implantation of recipients with complex congenital heart disease can usually be accomplished by harvesting additional donor pulmonary artery, aorta, and caval tissue to replace deficient recipient tissue or to correct malposition of the vena cava or great arteries. ,


There are generally two standard implantation techniques, classified by use of either a biatrial or bicaval anastomosis. In both techniques, left atrial tissue surrounding the recipient pulmonary veins is anastomosed to the donor left atrium. This is done to reduce implantation time and to avoid individual pulmonary vein anastomoses and subsequent stenosis. The traditional biatrial technique uses a relatively large cuff of recipient right and left atrial tissue anastomosed to a portion of both donor atria. This results in the presence of large atrial suture lines that can be a source for arrhythmia; possible injury to the sinus node, causing bradycardia; and atrial dilation resulting in alterations of atrial contractility, tricuspid valve function, and flow dynamics. This technique is primarily now used for infants and small children to avoid end-to-end anastomoses with small venae cavae or for patients with venous anomalies in which using the recipient atria is beneficial to the transplant. The newer bicaval technique removes the recipient right atrium and a large portion of the left atrium with preservation of the superior and inferior venae cavae and a cuff of tissue around the pulmonary veins. , End-to-end anastomoses of recipient and donor venae cavae are then used. This technique has the advantage of preserving sinus node function and atrial geometry.


Besides the issues discussed earlier, other intraoperative considerations include the administration of immunosuppressants during or immediately after implantation, delivery of inhaled nitric oxide (iNO) to support the donor right ventricle following implantation, and intraoperative plasmapheresis for any HLA antibody concerns. In the event of acute graft dysfunction and inability to separate from bypass, or for any other concerns about graft function, the use of temporary mechanical circulatory support should be considered.


Early perioperative management


The early perioperative management of the recipient is not significantly different from the management of any postcardiac surgical patient. The physiologic responses of the newly transplanted heart are altered because of denervation. The major changes related to autonomic denervation include diastolic dysfunction and exaggerated response to exogenously administered catecholamines. The transplanted heart must also adapt to a new environment related to recipient lung function and elevated PVR.


Autonomic system denervation results in a relatively fixed heart rate without respiratory variation. Heart rates are between 90 and 110 beats per minute but can be faster because of exogenous catecholamine administration. Heart rates can also be slower if the recipient has been exposed to amiodarone before transplantation or if there was injury to the donor sinus node due to cold preservation or to disruption of blood supply. Temporary pacing or isoproterenol infusion may be needed to support heart rate and cardiac output during the postoperative period. Permanent pacing is rarely necessary.


Early blood pressure instability is common because of loss of baroreceptor regulation and dependence of the transplanted heart on endogenous or exogenous catecholamines. Hypotension can have multiple causes, most related to the usual postcardiac bypass surgery issues. In addition, hypotension can be seen with primary graft dysfunction (discussed more later) and with vasoplegia in patients with a history of prolonged milrinone or amiodarone use.


Hypertension in the perioperative period has multiple causes. An increased stroke volume from the healthier transplanted heart into a systemic vascular bed that is abnormal because of a long-standing increase in SVR secondary to chronic heart failure is one such cause. Donor hearts are also often oversized, resulting in a larger stroke volume. This larger stroke volume can contribute to hypertension and to hyperperfusion syndrome, a condition in which an acute increase in cardiac output increases cerebral blood flow, resulting in cerebral vasoconstriction, symptomatic seizures, headache, or changes in mental status in a patient with a previously low cardiac output. The oversized donor heart eventually undergoes remodeling with regression of hypertrophy. The use of steroids for immunosuppression is an additional cause of posttransplant hypertension. Any symptomatic hypertension should be treated aggressively early in the perioperative period, but hypotension should be avoided in order to reduce the risk of renal dysfunction.


Systolic and/or diastolic dysfunction of the transplanted heart are often seen in the early postoperative period. The right ventricle is especially at risk owing to its susceptibility to preservation injury with thinner myocardium and increased myocardial stress from elevated PVR. Infusions of β-adrenergic agents for several days are often necessary to maintain optimal heart allograft function, as early myocardial function of the transplanted heart is dependent on catecholamine support. Milrinone, as well as other agents that improve contractility or decrease afterload, may be advantageous to support right ventricular function.


The hemodynamics of the transplanted heart reflect a significant shift to the left of the pressure/volume curve such that small increases in preload can result in significant elevations in ventricular end-diastolic and atrial pressures. Diastolic dysfunction is a significant impediment to early allograft function, limiting cardiac output. Some degree of diastolic dysfunction can persist well into the recovery phase and even several months after transplantation, with biopsy specimens often displaying evidence of persistent preservation injury.


Management of early heart allograft dysfunction


Early allograft dysfunction may be related to unsuspected injury prior to organ procurement or because of preservation injury. The other major cause of primary allograft failure is elevated PVR in the recipient. Allograft failure rarely is caused by acute antibody-mediated injury.


Donor risk factors for allograft dysfunction include “down time of the donor” (length of initial resuscitation), evidence of myocardial injury with elevation of troponin or ventricular dysfunction on echocardiogram, and use of high-dose inotropic support (dopamine/dobutamine >20 μg/kg per minute or epinephrine/norepinephrine >0.1 μg/kg per minute) in the donor. Abnormal heart function seen in the midst of the catecholamine storm of brain death can recover. Repeating the echocardiogram remote from the initial resuscitation period or after the reduction or discontinuation of inotropic support can increase confidence in accepting the donor heart.


The other major reason for primary donor heart dysfunction is right heart failure from high PVR. We have known since the early days of heart transplantation that the donor right ventricle will not function well when exposed to an abnormal pulmonary circulation. High PVR in the recipient increases perioperative morbidity and mortality and can affect late survival. Potential heart recipients generally undergo cardiac catheterization before heart transplantation to document the anatomy of systemic and pulmonary venous connections, determine pulmonary artery size and distribution, and calculate PVR. The upper limit of PVR associated with successful orthotopic heart transplantation is not known. Criteria developed from the adult heart transplant experience indicate that a PVR greater than 6 Wood units or a transpulmonary gradient (pulmonary artery mean pressure minus left atrial mean pressure) greater than 15 mm Hg is associated with increased perioperative mortality. The transpulmonary gradient is the most useful surrogate for PVR because estimation of cardiac output in the catheterization laboratory can be flawed if using the Fick equation. In children, the PVR index (PVRI), determined by dividing the transpulmonary gradient by the cardiac index, is more useful, because children come in all sizes. A PVRI less than 6 index units is associated with low perioperative mortality. Orthotopic heart transplants have been successful with a PVRI greater than 6 and as high as 10 index units but with increased morbidity and mortality rates. The diagnosis of high PVR is evident as the recipient is weaned from cardiopulmonary bypass. Intraoperative transesophageal echocardiography demonstrates dilation of the right ventricle and a small, underfilled left heart. Acute management of high PVR and right heart dysfunction includes ventilation with a high fraction of inspired oxygen and administration of iNO at 20 to 40 ppm. The need for continuous pulmonary vasodilator medications in the immediate perioperative period is unusual, but prostacyclin and sildenafil have both proved effective in this situation.


Immunosuppression and heart allograft rejection


It is imperative that immunosuppression be initiated early after heart transplantation. Solid-organ transplants transfer antigen-presenting cells (APCs) that are recognized as foreign by the recipient’s HLA immune system, which sets up a cascade of lymphocyte stimulation and proliferation. These lymphocytes then migrate to the heart allograft, where they can adhere to myocytes and endothelial receptors and cause tissue destruction. T-cell activation is the prime promoter of allograft rejection. The initial signal is T-cell receptor binding of antigen on the surface of an APC. The APC is derived from the donor in the form of a monocyte, or a tissue macrophage. Interaction of the APC and T-cell receptor causes release of interleukin (IL)-1 from the APC, which activates the T cell. Activated T cells secrete IL-2 and other lymphokines that induce proliferation of activated T cells, which migrate to the allograft and cause tissue damage.


Immunosuppression protocols are similar from center to center with generally only small variations. Initial immunosuppression protocols typically include high-dose corticosteroids, induction with IL-2 receptor blockade (e.g., basiliximab) or antithymocyte globulin (ATG), followed within approximately 48 hours by introduction of a calcineurin inhibitor (CNI), such as cyclosporine or tacrolimus ( Table 37.1 ).


Jun 26, 2021 | Posted by in CRITICAL CARE | Comments Off on Cardiac transplantation
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