1. Who performed the first experimental heart-lung transplant?

Show answer
Alexis Carrel, a French-born American surgeon, developed the vascular techniques required for heart-lung transplantation and performed the first experimental heart-lung transplant in 1907. He transplanted the lungs, heart, aorta, and vena cava of a 1-week-old cat into the neck of a large adult cat. For devising the technique of vascular anastomosis and other outstanding accomplishments, Carrel received the Nobel Prize in 1912 (the first Nobel Prize awarded to a scientist working in an American laboratory).

2. Who performed the first successful experimental heart-lung transplant?

Show answer
V.P. Demikhov performed the first successful heart-lung transplant in a dog in 1962.

3. Who developed the surgical strategy required for human heart transplantation?

Show answer
Norman Shumway.

4. Who performed the first human heart transplant? When?

Show answer
C.N. Bernard performed the first human heart transplant in December, 1967 (in Capetown, South Africa, after visiting Dr. Shumway), although Dr. Shumway set the stage by developing the technique in animals. Shumway and the Stanford group performed the first heart transplant in the United States and accomplished the first successful clinical series.

5. Who performed the first successful heart-lung transplant? When?

Show answer
Dr. Bruce Reitz at Stanford in 1981 on a 21-year-old woman with pulmonary hypertension secondary to an atrial septal defect.

6. How many heart transplants are performed annually? Is the number increasing or decreasing?

Show answer
In 1983 approximately 300 heart transplants were performed worldwide. By 1988, the number had rapidly increased to approximately 3000 and remains relatively stable between 3500 and 4000.

7. What anastomoses (surgical connections) must be performed for a combined heart and lungs transplant?

Show answer
The operation requires only a right atrial-to-cava (inflow) anastomosis and an aortic (outflow) anastomosis with a connection at the trachea. Heart-lung transplant is less complicated (fewer anastomoses) than heart transplant alone, which may explain why heart-lung transplant was attempted first.
8. What anastomoses must be performed for a heart transplant? Show answer
Left atrial, right atrial, aortic, and pulmonary arterial.

9. Who is an acceptable cardiac donor?

Show answer

Acceptable cardiac donors meet the following criteria:

1. Requirements for brain death
2. Consent from next of kin
3. ABO blood group compatibility with recipient
4. Within 20% of the same size as recipient
5. Absence of history of cardiac disease
6. Normal echocardiogram (ventricular wall motion)
7. Normal heart by inspection during organ recovery

10. Who is an acceptable cardiac recipient?

Show answer
Although selection criteria are evolving as a result of improved techniques and outcomes, the following criteria are standard: age between newborn and 65 years; irremediable New York Heart Association Functional Class IV cardiac disease; normal renal, hepatic, pulmonary, and central nervous system function; pulmonary vascular resistance < 6-8 Wood units; and absence of malignancy, infection, recent pulmonary infarction, and severe peripheral vascular or cerebrovascular disease. Diabetes is a relative contraindication; the steroids used in posttransplant immunosuppression make diabetes difficult to manage. Also, normal psychological status has proven to be important.

11. What are the most common indications for heart transplant in adults and in children?

Show answer
In adults, coronary artery disease (ischemic cardiomyopathy) and idiopathic cardiomyopathy each account for approximately 45% of transplants.
In children, congenital heart disease and cardiomyopathy are most common, with hypoplastic left heart being the most common congenital malformation requiring heart transplantation.

12. What percentage of potential recipients (on the transplant list) die while waiting for a heart transplant?

Show answer
20%.

13. At what point does donor heart ischemic time influence mortality?

Show answer
Donor heart ischemic time > 6 hours definitely increases mortality. Ischemic times between 4 and 6 hours stun the donor heart. Most transplant teams try to keep ischemic times (from donor harvest to perfusion in the recipient) to < 4 hours.

14. Who pioneered hypothermic myocardial preservation?

Show answer
Henry Swan at the University of Colorado. He submerged anesthetized children in a bathtub of ice water before cardiac procedures.

15. How is cardiac allograft rejection prevented?

Show answer
Pharmacologically induced immunosuppression is performed by using one of two protocols. The first is triple therapy, which combines cyclosporine, azathioprine, and prednisone. The second major protocol incorporates the monoclonal antibody OKT3 into the triple therapy protocol. OKT3 is substituted for cyclosporine for the first 2 weeks after transplant.

16. What is OKT3?

Show answer
OKT3 is a mouse monoclonal antibody that binds to and blocks the T-cell CD3 receptor. A monoclonal antibody is an antibody generated from the clones of a single cell. For instance, a single B cell, which recognizes the CD3 receptor as an antigen (foreign), is immortalized in cell culture and produces the monoclonal antibody in limitless supply. The CD3 receptor, which is common to all T cells, is important for antigen recognition and T-cell activation; therefore, OKT3 is highly immunosuppressive.
KEY POINTS: CRITERIA FOR ACCEPTABLE HEART DONORS

1. Donors must meet the criteria for brain death.
2. Consent from donor’s next of kin.
3. ABO blood group compatibility with recipient.
4. Donor must be within 20% of same size as recipient.
5. Donor must have no history of cardiac disease and a normal echocardiogram.
6. Donor heart must appear normal by inspection during organ recovery.

17. What complications are associated with the use of OKT3?

Show answer
OKT3 may have severe side effects, including pulmonary edema and high fevers, that result from transient cytokine release, which may occur when OKT3 binds to the T-cell activation site. Because OKT3 is an antigen (an antibody from a different species [i.e., a mouse]), patients develop anti-OKT3 antibodies fairly quickly; the result is that OKT3 can only be used to treat one rejection episode. Severe side effects occur in < 5% of patients.

18. Does HLA mismatch influence the incidence of rejection after heart transplantation? Is HLA typing routinely performed before heart transplantation?

Show answer
Yes and no. In a multi-institutional, multivariate analysis of 1719 cardiac transplant recipients by Jarcho et al., HLA mismatch increased the incidence of rejection. However, HLA typing is not routinely done before heart transplantation because it takes too long. In addition, with three of six mismatches, there was still only a trend toward increased rejection-related deaths (P = 0.14). If longer organ preservation times can be achieved, donor/recipient HLA matching will become feasible and should improve survival rates. Again, ABO blood group compatibility does influence graft survival.

19. What are the major complications of heart transplantation?

Show answer

* Allograft rejection (days to weeks)
* Infection (months)
* Transplant coronary artery disease (years)

20. What is the incidence of transplant coronary artery disease? What are the risk factors?

Show answer
Nearly 50% of patients have angiographic evidence of coronary artery disease by 5 years after transplant. However, only approximately 10% develop at least 70% stenosis (hemodynamically significant stenosis). Severe stenosis is highly predictive of the need for retransplantation. Risk factors for transplant coronary artery disease include male gender of the donor or recipient, older donor age, and donor hypertension.

21. How is cardiac allograft rejection diagnosed?

Show answer
Clinical suspicion is raised by new-onset cardiac arrhythmia, fever, or hypotension. Diagnosis depends on endomyocardial biopsy, which is performed at regular intervals to detect histologic evidence of rejection before signs or symptoms occur. Radionuclide ventriculography and echocardiography are useful adjuncts in following the hemodynamic manifestations of rejection. Electrocardiography itself is not very sensitive in the diagnosis of rejection.

22. Are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (”statin” drugs) generally recommended for post-cardiac transplant patients?

Show answer
Yes. Hypercholesterolemia is common after transplantation, and HMG-CoA reductase inhibitors reduce the development of the diffuse atherosclerosis that tends to occur in transplanted hearts. In addition, statins have an early effect on mortality, which suggests that these drugs may also have immunosuppressive effects.

23. What are ventricular assist devices (VADs)?

Show answer
These devices are designed to unload either the right (RVAD) or left (LVAD) ventricle while supporting the pulmonary or systemic circulation. Patients with these VADs may be ambulatory, and the devices may be worn for weeks to months. VADs may be used as a bridge to transplant (when the patient is listed for transplantation) or as destination therapy (when no transplant is planned).

24. What is the most serious complication of transvenous endomyocardial biopsy?

Show answer
Cardiac perforation occurs in 0.5% of cases. This can rapidly lead to tamponade and circulatory collapse.

25. What is the typical infection pattern for a posttransplant patient?

Show answer

* First postoperative month: conventional bacterial pathogens encountered in surgical patients
* 1-4 months: opportunistic pathogens, especially cytomegalovirus
* >4 months: both conventional and opportunistic infections

26. Is the transplanted heart denervated?

Show answer
Initially, yes, but it is believed that partial reinnervation begins within 1 year. Because of this, the heart’s anatomically mediated reflexes are blunted (e.g., higher resting heart rate because of decreased or absent vagal tone).

27. Can one heart be successfully transplanted twice?

Show answer
Yes. Meiser et al. transplanted the same heart a second time on March 19, 1991, 42 hours after the initial transplantation. Second transplant of the same heart has since been reported by others.

28. What is “domino heart transplant”?

Show answer
The good heart from a heart-lung recipient is transplanted into a patient requiring a heart transplant. Some patients with primary lung dysfunction have secondary irreversible cardiac dysfunction (i.e., Eisenmenger’s syndrome); others, however, such as patients with cystic fibrosis, have good cardiac function. Patients with good cardiac function may serve as donors and increase the donor pool.

29. Is the heart capable of making tumor necrosis factor (TNF)? What does TNF have to do with heart transplantation?

Show answer
TNF, typically described as a macrophage- or monocyte-derived inflammatory cytokine, is also produced in large quantities by the heart. TNF released by the heart after ischemia-reperfusion probably contributes to immediate injury (dysfunction) and possibly to later rejection. Anti-TNF strategies are intuitively promising (but undocumented) therapeutic strategies.

30. What is the overall 30-day mortality rate after heart transplant? What is the breakdown in mortality between adult and pediatric patients?

Show answer
The registry of the International Society for Heart and Lung Transplantation, which has data for approximately 45,000 heart transplants, has recorded a 30-day mortality rate of 10%. The 30-day mortality rate for adult recipients is about 8%; for pediatric recipients, it is slightly higher.

31. What are the 5- and 10-year actuarial survival rates for heart transplant recipients?

Show answer

75% and 50%, respectively (and the quality of life is dramatically improved).
32. What work remains to be done in heart transplantation?

Show answer
The future of heart transplantation is bright. Knowledge gained in experimental myocardial ischemia-reperfusion injury and protection is accelerating. New, exciting ways to manipulate myocardial immunology (e.g., signal transduction, gene therapy, chimerism) will further extend donor ischemic times and improve postoperative myocardial function and graft tolerance. Ultimately, genetic alteration of donor hearts will increase the donor pool.

References
WEB SITE
http://www.transplantation-soc.org
BIBLIOGRAPHY
1. Hosenpud JD, Bennett LE, Keck BM, et al: The Registry of the International Society for Heart and Lung Transplantation: Eighteenth official report-2001. J Heart Lung Transplant 20:805-815, 2001.
2. Kobashigawa JA: Advances in immunosuppression for heart transplantation. Adv Card Surg 10:155-174, 1998. Medline Similar articles
3. Kupiec-Weglinski JW: Graft rejection in sensitized recipients. Ann Transplant 1:34-40, 1996. Medline Similar articles
4. Kuvin JT, Kimmelstiel CD: Infectious causes of atherosclerosis. Am Heart J 137:216-226, 1999. Medline Similar articles
5. Leier CV, Binkley PF: Parenteral inotropic support for advanced congestive heart failure. Prog Cardiovasc Dis 41:207-224, 1998.
6. Meldrum DR: Tumor necrosis factor in the heart [review]. Am J Physiol 274:R577, 1998. Medline Similar articles
7. Meldrum DR, Dinarello CA, Meng X, et al: Ischemic preconditioning decreases post-ischemic myocardial TNF: Potential ultimate effector mechanism of preconditioning. Circulation 98:II214-II218, 1998. Medline Similar articles
8. Mindan JP, Panizo A: Pathology of heart transplant. Curr Top Pathol 92:137-165, 1999. Similar articles
9. Orbaek Andersen H: Heart allograft vascular disease: An obliterative vascular disease in transplanted hearts. Atherosclerosis 142:243-263, 1999. Medline Similar articles
10. Pillai R, Bando K, Schueler S, et al: Leukocyte depletion results in excellent heart-lung function after 12 hours of storage. Ann Thorac Surg 50:211-214, 1990. Medline Similar articles
11. Reardon MJ, Letsou GV, Anderson JE, et al: Orthotopic cardiac transplantation after minimally invasive direct coronary artery bypass. J Thorac Cardiovasc Surg 117:390-391, 1999.
12. Spann JC, Van Meter C: Cardiac transplantation. Surg Clin North Am 78:679-690, 1998. Medline Similar articles

1. What are the general types of lung transplants?

Show answer
Single, double (bilateral), and heart-lung.

2. Which human organ transplant was performed first, the heart or the lung?

Show answer
Although heart transplantation has progressed more rapidly, the first lung transplant preceded the first heart transplant.

3. Who performed the first human lung transplant? When?

Show answer
James Hardy performed the first human lung transplant in 1963; however, more than 20 years passed before lung transplantation was performed routinely in clinical practice (during that 20 year period, only 1 patient did well enough to leave the hospital). This delay was caused by initial graft failure secondary to inadequate organ preservation, long ischemic times, lack of good immunosuppressive agents, and technical difficulties (primarily with the bronchial-not the vascular-anastomoses).

4. Who is a candidate for a lung transplant?

Show answer
Candidates include patients with no other medical or surgical alternative who are likely to die of pulmonary disease within 18 months, are younger than 65 years, are not ventilator dependent, and do not have a history of malignancy. Psychological stability in the recipient is also important.

5. What are the most common indications for single lung transplant?

Show answer

* Emphysema (40%)
* Idiopathic pulmonary fibrosis (20%)
* Alpha-1 antitrypsin deficiency (11%)
* Primary pulmonary hypertension and pulmonary hypertension secondary to correctable congenital heart disease (10%)

6. What are the most common indications for a double-lung transplant?

Show answer

* Cystic fibrosis (35%)
* Emphysema (20%)
* Alpha-1 antitrypsin deficiency (11%)
* Primary pulmonary hypertension and pulmonary hypertension secondary to correctable congenital heart disease (20%)
* Idiopathic pulmonary fibrosis (8%)

7. What are the most common indications for heart-lung transplant?

Show answer
Primary pulmonary hypertension (30%) and cystic fibrosis (16%) are instances in which bad lungs have ruined a good heart. Conversely, with congenital heart disease (27%), a bad heart has destroyed good lungs.

8. What is sewn to what during a single-lung transplant? A double-lung transplant?

Show answer
During a single-lung transplant, recipient-to-graft bronchial, pulmonary artery, and pulmonary vein (atrial cuff) anastomoses are required. Anastomoses for double transplant are the same; however, cardiopulmonary bypass is required more often during double-lung transplant. During implantation of the second lung, diversion of the entire cardiac output to the freshly ischemic lung often results in reperfusion lung edema and hypoxemia.

9. Which diagnoses carry the best results for single-lung transplants?

Show answer
Patients with emphysema and alpha-1 antitrypsin deficiency do significantly better, with 1-year survival rates of 80%.

10. Why is the number of combined heart-lung transplants performed annually decreasing?

Show answer
Approximately 250 heart-lung transplants were performed in 1990; the number has decreased to approximately 150 in 1999. As the results of single- and double-lung transplants have improved, the need to perform heart-lung transplants in patients with isolated pulmonary disease has been obviated.

11. What are the most common complications after lung transplant?

Show answer

* Airway surgical healing defects (early)
* Rejection (early)
* Bacterial and cytomegalovirus infections (weeks to months)
* Bronchiolitis obliterans (months to years)

12. What is bronchiolitis obliterans?

Show answer
Bronchiolitis obliterans, a major cause of long-term morbidity after lung transplantation, is a process in which membranous and respiratory bronchioles demonstrate histologic evidence of subepithelial scarring that eventually progresses to occlusion of the bronchiolar lumen. Clinically, it is characterized by dyspnea and airflow obstruction.

13. What are the risk factors for the development of bronchiolitis obliterans after lung transplant?

Show answer
Donor age > 40 years and donor ischemic times > 6 hours.

14. How is lung transplant rejection diagnosed?

Show answer
Unlike heart transplants, the diagnosis of rejection in transplanted lungs is imprecise and based on a collection of symptoms and signs. Decreased oxygen saturation, fever, decreased exercise tolerance, and radiologic infiltrate suggest rejection. Sequential quantitative lung perfusion scans that demonstrate a decrease in perfusion are helpful in the diagnosis of rejection after single-lung transplants. Transbronchial biopsy is useful after single- and double-lung transplants.

15. Describe the phenomenon of chimerism in transplantation.

Show answer
Chimerism is leukocyte sharing between the graft and the recipient so that the graft becomes a genetic composite of both the donor and recipient. Chimerism enhances the host’s tolerance of the graft because the recipient does not recognize the donor organ as foreign. The first evidence of chimerism was observed in 1969 when female recipients of male livers developed entirely female Kupffer cell (liver macrophage) systems (as demonstrated by the Barr bodies in the macrophage). In 1992, the concept of immune cell sharing became clinically evident when it was discovered that leukocytes from donor kidneys occupied remote lymph nodes.

16. Do resident macrophages exist in the heart and lungs?

Show answer
Absolutely yes. Resident myocardial macrophages and resident alveolar macrophages are incredibly active cellular components of the heart and lungs.

17. Does chimerism develop in the heart and the lungs?

Show answer
Yes. Because the heart and lungs each have leukocytes to share, they participate in chimerism.

18. Why is chimerism exciting?

Show answer
Nature is trying to teach us how to perform transplantation without the use of immunosuppression. Our job is to learn why chimerism is induced in some recipients and not in others. That is, we should dissect the mechanisms of chimerism induction so that we may therapeutically induce chimerism in all recipients.

19. What are the major types of preservation solutions for heart and lung grafts?

Show answer
Euro-Collins (EC) solution and University of Wisconsin (UW) solution for lung and crystalloid cardioplegia and UW solution for hearts.

20. What percentage of pulmonary blood flow goes to the transplanted lung after single-lung transplant?

Show answer
Predictably, almost all of the pulmonary blood flow passes through the lower resistance circuit of the transplanted lung (depending on the pulmonary vascular resistance of the contralateral native-i.e., sick-lung). If a preoperative perfusion scan exists, other factors being equal, the lung with the best perfusion is preserved and the bad lung is replaced.
KEY POINTS: LUNG TRANSPLANTATION

1. The most common indication for single lung transplant is emphysema.
2. The most common indication for double lung transplant is cystic fibrosis.
3. Chimerism is leukocyte sharing between the graft and the recipient so that the graft becomes a genetic composite of both donor and recipient.
4. Bronchiolitis obliterans, a major cause of long-term morbidity after lung transplantation, is a process in which membranous and respiratory bronchioles demonstrate histologic evidence of subepithelial scarring that eventually progresses to occlusion of the bronchiolar lumen.

21. Is cardiopulmonary bypass required for lung transplantation?

Show answer
No. However, for patients with pulmonary hypertension (primary or secondary), cardiopulmonary bypass is routinely used before removal of the recipient’s lung. Cardiopulmonary bypass is always on standby. This is tricky anesthesia. One lung is transiently excised from a patient who is living (barely) on two bad lungs.

22. Is living-related lung transplant possible?

Show answer
Yes. Living-related lung transplants are an innovative approach to increasing the donor pool. Typically, only one lobe from the donor is used to replace a whole lung in the recipient.

23. What is lung volume reduction surgery? How may it be important to patients on the lung transplant waiting list?

Show answer

Lung volume reduction surgery offers a therapeutic option for patients who are either not candidates to receive a lung transplant or on a long waiting list. Lung volume reduction surgery removes nonfunctional or destroyed lung. Removal of defunctionalized lung makes more room for airflow in the functional lung, thereby decompressing the distended chest.

24. Who is the best candidate for lung volume reduction surgery?

Show answer
The best candidates are patients without contraindication who have absent or reduced perfusion of approximately one third of the lung (usually caused by a big cyst or emphysematous region), with good flow distribution in the remainder of the lung. Thus, quantitative lung perfusion scans provide essential information for patient selection.

25. What are the contraindications to lung reduction surgery?

Show answer

* Pulmonary hypertension (mean pulmonary artery pressure [PAP] > 35 mmHg or systolic PAP > 45 mmHg)
* Significant coronary artery disease
* Previous thoracotomy or pleurodesis (visceral and parietal pleural fusion)
* Long-standing history of asthma, bronchiectasis, or chronic bronchitis with purulent sputum
* Severe kyphoscoliosis

26. What is the most common nonbacterial cause of pneumonia in lung transplant patients?

Show answer
Cytomegalovirus (CMV), usually occurring 4-8 weeks postoperatively. Primary CMV infection usually results in more serious illness than reactivation disease. CMV-seronegative recipients should receive only blood products that are serologically negative.

27. In addition to immune suppressive therapy, what other factors put transplanted lungs at risk for infection?

Show answer
Lung denervation, interruption of lymphatic clearance and bronchial circulation, and impaired mucociliary clearance.

28. What are the main differences in composition between EC and UW solutions?

Show answer
EC solution is a glucose-based solution with an ionic composition that approximates that of the intracellular environment.
UW solution does not contain glucose but does contain the following components not found in EC solution: hydroxy-ethyl starch (prevents expansion of the interstitial space), lactobionate and raffinose (suppress hypothermia-induced cell swelling), glutathione and allopurinol (reduce cytotoxic injury from oxygen free radicals), and adenosine (substrate for adenosine triphosphate formation, vasodilation, and activation of the protective mechanisms of “protective preconditioning”).

29. How many lung transplants are performed annually? Is the number increasing or decreasing?

Show answer
Of interest, although the first human lung transplant was performed in 1963, significant numbers were not performed until the late 1980s (in 1986, 1 lung transplant; in 1989, 132 lung transplants). This number rapidly increased to 700 per year in 1994 and has since declined to approximately 625 per year worldwide.

30. Are the survival rates different for single- and double-lung transplants?

Show answer
No. The 3-year actuarial survival rate is about 50% for each.

31. What are the 1-year, 2-year, and 3-year actuarial survival rates for single-lung retransplants?

Show answer
Actuarial survival rates are 45%, 40%, and 30%, respectively. Predictably, such patients do significantly worse.

References
WEB SITE
http://www.transplantation-soc.org
BIBLIOGRAPHY
1. Baumgartner WA: Myocardial and pulmonary protection: Long-distance transport. Prog Cardiovasc Dis 33:85-96, 1990. Medline Similar articles
2. Christie JD, Bavaria JE, Palevsky HI, et al: Primary graft failure following lung transplantation. Chest 114:51-60, 1998.
3. Cooper JD, Patterson GA: Lung transplantation. In Sabiston D, Spencer F (eds): Surgery of the Chest, 7th ed. Philadelphia, W.B. Saunders, 1995, pp 2117-2134.
4. Gaynor JW, Bridges ND, Clark BJ, et al: Update on lung transplantation in children. Curr Opin Pediatr 10:256-261, 1998. Medline Similar articles
5. Hosenpud JD, Bennett LE, Keck BM, et al: The Registry of the International Society for Heart and Lung Transplantation: Eighteenth official report-2001. J Heart Lung Transplant 20:805-815, 2001.
6. Keller CA: The donor lung: Conservation of a precious resource. Thorax 53:506-513, 1998. Medline Similar articles
7. Meyers BF, Patterson GA: Technical aspects of adult lung transplantation. Semin Thorac Cardiovasc Surg 10:213-220, 1998.
8. Nunley DR, Grgurich W, Iacono AT, et al: Allograft colonization and infections with pseudomonas in cystic fibrosis lung transplant recipients. Chest 113:1235-1243, 1998. Medline Similar articles
9. Rich S, McLaughlin VV: Lung transplantation for pulmonary hypertension: Patient selection and maintenance therapy while awaiting transplantation. Semin Thorac Cardiovasc Surg 10:135-138, 1998.
10. Sundaresan S: The impact of bronchiolitis obliterans on late morbidity and mortality after single and bilateral lung transplantation for pulmonary hypertension. Semin Thorac Cardiovasc Surg 10:152-159, 1998. Medline Similar articles
11. Waddell TK, Keshavjee S: Lung transplantation for chronic obstructive pulmonary disease. Semin Thorac Cardiovasc Surg 10:191-201, 1998. Similar articles
12. Zenati M, Keenan RJ, Courcoulas AP, et al: Lung volume reduction or lung transplanation for end-stage pulmonary emphysema? Eur J Cardiothorac Surg 14:27-31, 1998.

1. Who performed the first experimental heart-lung transplant?

Show answer
Alexis Carrel, a French-born American surgeon, developed the vascular techniques required for heart-lung transplantation and performed the first experimental heart-lung transplant in 1907. He transplanted the lungs, heart, aorta, and vena cava of a 1-week-old cat into the neck of a large adult cat. For devising the technique of vascular anastomosis and other outstanding accomplishments, Carrel received the Nobel Prize in 1912 (the first Nobel Prize awarded to a scientist working in an American laboratory).

2. Who performed the first successful experimental heart-lung transplant?

Show answer
V.P. Demikhov performed the first successful heart-lung transplant in a dog in 1962.

3. Who developed the surgical strategy required for human heart transplantation?

Show answer
Norman Shumway.

4. Who performed the first human heart transplant? When?

Show answer
C.N. Bernard performed the first human heart transplant in December, 1967 (in Capetown, South Africa, after visiting Dr. Shumway), although Dr. Shumway set the stage by developing the technique in animals. Shumway and the Stanford group performed the first heart transplant in the United States and accomplished the first successful clinical series.

5. Who performed the first successful heart-lung transplant? When?

Show answer
Dr. Bruce Reitz at Stanford in 1981 on a 21-year-old woman with pulmonary hypertension secondary to an atrial septal defect.

6. How many heart transplants are performed annually? Is the number increasing or decreasing?

Show answer
In 1983 approximately 300 heart transplants were performed worldwide. By 1988, the number had rapidly increased to approximately 3000 and remains relatively stable between 3500 and 4000.

7. What anastomoses (surgical connections) must be performed for a combined heart and lungs transplant?

Show answer
The operation requires only a right atrial-to-cava (inflow) anastomosis and an aortic (outflow) anastomosis with a connection at the trachea. Heart-lung transplant is less complicated (fewer anastomoses) than heart transplant alone, which may explain why heart-lung transplant was attempted first.

8. What anastomoses must be performed for a heart transplant?

Show answer
Left atrial, right atrial, aortic, and pulmonary arterial.

9. Who is an acceptable cardiac donor?

Show answer

Acceptable cardiac donors meet the following criteria:

1. Requirements for brain death
2. Consent from next of kin
3. ABO blood group compatibility with recipient
4. Within 20% of the same size as recipient
5. Absence of history of cardiac disease
6. Normal echocardiogram (ventricular wall motion)
7. Normal heart by inspection during organ recovery

10. Who is an acceptable cardiac recipient?

Show answer
Although selection criteria are evolving as a result of improved techniques and outcomes, the following criteria are standard: age between newborn and 65 years; irremediable New York Heart Association Functional Class IV cardiac disease; normal renal, hepatic, pulmonary, and central nervous system function; pulmonary vascular resistance < 6-8 Wood units; and absence of malignancy, infection, recent pulmonary infarction, and severe peripheral vascular or cerebrovascular disease. Diabetes is a relative contraindication; the steroids used in posttransplant immunosuppression make diabetes difficult to manage. Also, normal psychological status has proven to be important.

11. What are the most common indications for heart transplant in adults and in children?

Show answer
In adults, coronary artery disease (ischemic cardiomyopathy) and idiopathic cardiomyopathy each account for approximately 45% of transplants.
In children, congenital heart disease and cardiomyopathy are most common, with hypoplastic left heart being the most common congenital malformation requiring heart transplantation.

12. What percentage of potential recipients (on the transplant list) die while waiting for a heart transplant?

Show answer
20%.

13. At what point does donor heart ischemic time influence mortality?

Show answer
Donor heart ischemic time > 6 hours definitely increases mortality. Ischemic times between 4 and 6 hours stun the donor heart. Most transplant teams try to keep ischemic times (from donor harvest to perfusion in the recipient) to < 4 hours.

14. Who pioneered hypothermic myocardial preservation?

Show answer
Henry Swan at the University of Colorado. He submerged anesthetized children in a bathtub of ice water before cardiac procedures.

15. How is cardiac allograft rejection prevented?

Show answer
Pharmacologically induced immunosuppression is performed by using one of two protocols. The first is triple therapy, which combines cyclosporine, azathioprine, and prednisone. The second major protocol incorporates the monoclonal antibody OKT3 into the triple therapy protocol. OKT3 is substituted for cyclosporine for the first 2 weeks after transplant.

16. What is OKT3?

Show answer
OKT3 is a mouse monoclonal antibody that binds to and blocks the T-cell CD3 receptor. A monoclonal antibody is an antibody generated from the clones of a single cell. For instance, a single B cell, which recognizes the CD3 receptor as an antigen (foreign), is immortalized in cell culture and produces the monoclonal antibody in limitless supply. The CD3 receptor, which is common to all T cells, is important for antigen recognition and T-cell activation; therefore, OKT3 is highly immunosuppressive.

KEY POINTS: CRITERIA FOR ACCEPTABLE HEART DONORS

1. Donors must meet the criteria for brain death.
2. Consent from donor’s next of kin.
3. ABO blood group compatibility with recipient.
4. Donor must be within 20% of same size as recipient.
5. Donor must have no history of cardiac disease and a normal echocardiogram.
6. Donor heart must appear normal by inspection during organ recovery.

17. What complications are associated with the use of OKT3?

Show answer
OKT3 may have severe side effects, including pulmonary edema and high fevers, that result from transient cytokine release, which may occur when OKT3 binds to the T-cell activation site. Because OKT3 is an antigen (an antibody from a different species [i.e., a mouse]), patients develop anti-OKT3 antibodies fairly quickly; the result is that OKT3 can only be used to treat one rejection episode. Severe side effects occur in < 5% of patients.

18. Does HLA mismatch influence the incidence of rejection after heart transplantation? Is HLA typing routinely performed before heart transplantation?

Show answer
Yes and no. In a multi-institutional, multivariate analysis of 1719 cardiac transplant recipients by Jarcho et al., HLA mismatch increased the incidence of rejection. However, HLA typing is not routinely done before heart transplantation because it takes too long. In addition, with three of six mismatches, there was still only a trend toward increased rejection-related deaths (P = 0.14). If longer organ preservation times can be achieved, donor/recipient HLA matching will become feasible and should improve survival rates. Again, ABO blood group compatibility does influence graft survival.

19. What are the major complications of heart transplantation?

Show answer

* Allograft rejection (days to weeks)
* Infection (months)
* Transplant coronary artery disease (years)

20. What is the incidence of transplant coronary artery disease? What are the risk factors?

Show answer
Nearly 50% of patients have angiographic evidence of coronary artery disease by 5 years after transplant. However, only approximately 10% develop at least 70% stenosis (hemodynamically significant stenosis). Severe stenosis is highly predictive of the need for retransplantation. Risk factors for transplant coronary artery disease include male gender of the donor or recipient, older donor age, and donor hypertension.

21. How is cardiac allograft rejection diagnosed?

Show answer
Clinical suspicion is raised by new-onset cardiac arrhythmia, fever, or hypotension. Diagnosis depends on endomyocardial biopsy, which is performed at regular intervals to detect histologic evidence of rejection before signs or symptoms occur. Radionuclide ventriculography and echocardiography are useful adjuncts in following the hemodynamic manifestations of rejection. Electrocardiography itself is not very sensitive in the diagnosis of rejection.

22. Are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (”statin” drugs) generally recommended for post-cardiac transplant patients?