Thoracic organ transplantation: an overview for perfusionists

1
Thoracic organ transplantation an overview for
perfusionists

• Andreas Hoschtitzky

2
Overview

• OCTx
• HCTx
• HLTx
• DLTx
• SLTx

3
History OCTx

• 1905 Alexis Carrel transplanted a puppy's heart
  into the neck of a dog because of the lack of
  immunosuppression, the experiment was
  unsuccessful.
• Early investigators included Frank C. Mann of the
  Mayo Clinic, V.P. Demikov of the Soviet Union,
  and Marcus Wong. These early efforts in
  transplantation were thwarted by the infancy of
  cardiopulmonary bypass and a lack of
  understanding of the immune system. As knowledge
  in these areas advanced, so did the field of
  cardiac transplantation.
• Shumway developed modern day transplantation
  protocols.
• 1967 Christian Barnard first successful heart
  transplant in a human.
• 1983 The clinical use of cyclosporine as an
  immunosuppressant revolutionized the field of
  transplantation. Recipient survival rates
  improved, thus producing an explosive increase in
  the number of transplant centers offering cardiac
  transplantation.
• The remaining limiting factor number of
  available organ donors.

4
OCTx transplantation

• Indications patients with end-stage congestive
  heart failure with a prognosis of less than a
  year to live without the transplant and who are
  not candidates for conventional medical therapy
  or have not been helped by conventional medical
  therapy.
• In the US approximately 4000 individuals are
  waiting for hearts. In 1999, about 2000 heart
  transplants were performed in the US. UK around
  300-400 per year.
• Availability of organs is a major issue.

5
OCTx transplantation

• Frequency The annual frequency of the procedure
  is about 1 of the general population with heart
  failure
• Etiology
• adults
• Idiopathic cardiomyopathy 54
• Ischemic cardiomyopathy 45
• Congenital heart disease
• and other diseases 1
• children congenital heart disease and
  cardiomyopathy most common HLHS commonest

6
Pathophysiology OCTx

• Transplanted heart is unique
• denervation of the organ makes it dependent on
  its intrinsic rate.
• as a result of the lack of neuronal input, some
  left ventricular hypertrophy results.
• right ventricular function is directly dependent
  upon ischaemic time and adequacy of preservation.
  
• right ventricle is easily damaged and may
  initially function as a passive conduit until
  recovery occurs.
• Allograft rejection 2 forms cellular and
  humoral.
• Cellular rejection is the classic form of
  rejection perivascular infiltration of
  lymphocytes with subsequent myocyte damage and
  necrosis if left untreated.
• Humoral rejection is much more difficult to
  characterize and diagnose. Generalized antibody
  response initiated by several unknown factors.
  The antibody deposition into the myocardium
  results in global cardiac dysfunction. Diagnosis
  is generally made on the basis of clinical
  suspicion and exclusion because endomyocardial
  biopsy is of little value.
• Coronary artery disease late process, common to
  all cardiac allografts.
• Diffuse myointimal hyperplasia of the small- and
  medium-sized vessels, occuring from 3 months to
  several years after implantation.
• Etiology still unclear, though cytomegalovirus
  (CMV) infection and chronic rejection have been
  implicated. The mechanism of the process is
  thought to be dependent upon growth-factor
  production in the allograft initiated by
  circulating lymphocytes. Treatment
  re-transplantation.

7
Indications OCTx

• Deteriorating cardiac function and having a
  prognosis of less than 1 year to live NYHA class
  III or IV symptoms
• EF lt 25
• Intractable angina or malignant cardiac
  arrhythmias for which conventional therapy has
  been exhausted
• PVR lt 6-8 Wood units
• Age lt 65 years
• Normal renal, hepatic, pulmonary and CNS function
• Absence of malignancy, infection, recent
  pulmonary infarct, severe peripheral vascular or
  cerebro-vascular disease
• Ability to comply with medical follow-up care

8
OCTx Donor criteria

• Brain death
• Consent next of kin
• ABO compatible with recipient gt 1year old
• Within 20 size as recipient
• No cardiac disease in medical history
• Normal ventricular wall motion on ECHO
• Normal heart as assessed by donor team

9

• 20 recipients die on waiting list though.

10
Management of the Potential Cardiac Recipient

• TAILORED MEDICAL THERAPY FOR END-STAGE CARDIAC
  FAILURE
• Conventional outpatient management of congestive
  heart failure includes ACE inhibitors, AR
  blockers, beta blockers, and diuretics
  (especially spironolactone).
• PHARMACOLOGIC BRIDGE TO TRANSPLANTATION
• Critically compromised patients require
  admission to the intensive care unit for
  intravenous inotropic therapy. Milrinone,
  dobutamine, and dopamine are the agents of
  choice. Placement of an intra-aortic balloon pump
  (IABP) also may be necessary in heart failure
  refractory to initial pharmacologic measures.
  Patients with continued pulmonary congestion or
  global hypoperfusion despite maximal
  pharmacologic and IABP therapies have been shown
  to improve with placement of mechanical devices
  as bridges to transplantation.
• MECHANICAL BRIDGE TO TRANSPLANTATION
• The increased success of cardiac transplantation
  in conjunction with the static number of
  available organs has created a need for
  mechanical assist devices as a bridge to
  transplantation. Ventricular assist devices (VAD)
  or total artificial hearts (TAH) may be indicated
  in potential cardiac recipients who remain
  unstable after 24 to 48 hours of maximal
  pharmacologic support. Since these devices are
  rarely weaned, however, it is imperative that the
  patient's candidacy for transplantation be
  scrutinized prior to placement of a VAD or TAH.
  Patient selection for a mechanical device is a
  complex, evolving field. Recent data shows that
  approximately 70 of patients are successfully
  bridged to transplantation and the actuarial
  survival is 80 at one year. Most large series
  suggest an improvement in survival because the
  devices allow patients to be rehabilitated while
  on the device. Initial results from the
  Randomized Evaluation of Mechanical Assistance
  for the Treatment of Congestive Heart Failure
  (REMATCH) study indicate that patients with
  devices have improved survival and quality of
  life at 1 year compared to medical therapy and
  may prove to be an acceptable long term option in
  those patients who are not candidates for cardiac
  transplantation.
• LIFE-THREATENING VENTRICULAR ARRHYTHMIAS
• Symptomatic VT or VF and a history of sudden
  cardiac death (SCD) are indications for placement
  of an automatic implantable cardioverter-defibrill
  ator (AICD), long-term amiodarone therapy, or
  occasionally radiofrequency catheter ablation.
  SCD is the most common cause of death in patients
  awaiting heart transplantation and is most common
  within the first 3 months after referral for
  transplantation. Several studies have shown that
  implantation of a defibrillator improved survival
  in patients with either a history of or inducible
  ventricular tachycardia or fibrillation.

11
Management of the Cardiac Donor

• Complex physiological phenomenon of brain death
  and the need to coordinate procurement with other
  organ donor teams. Optimal care requires that the
  donor be treated as any other intensive care unit
  patient with invasive hemodynamic monitoring,
  ventilatory support, and meticulous attention to
  intravascular volume status and electrolytes.
• Continuous monitoring of arterial pressure,
  central venous pressure, and urinary output is
  mandatory. As the number of marginal donors
  increases with the acceptance of more lenient
  eligibility criteria, some transplant centers
  have established mobile intensive care teams that
  are dispatched to ensure appropriate management
  of these highly labile patients.
• Haemodynamic instability in the donor may result
  from vasomotor dysfunction, hypovolemia,
  hypothermia, and dysrhythmias. Increased
  intracranial pressure may lead to massive
  sympathetic discharge with elevated levels of
  circulating endogenous catecholamines. The
  resultant episodes of systemic hypertension and
  coronary vasospasm place the allograft at
  significant risk of ischemic injury. Rapid
  afterload reduction may be achieved with sodium
  nitroprusside, whereas volatile anesthetics
  assist in reducing the intensity of sympathetic
  bursts. To minimize cerebral edema prior to the
  declaration of brain death, potential donors have
  been intravascularly volume depleted via strict
  fluid restriction and osmotic diuresis.
  Aggressive volume resuscitation is sometimes
  necessary and may require use of a Swan-Ganz
  catheter.
• Fluid overload, however, should be avoided to
  prevent postoperative allograft dysfunction
  caused by chamber distention and myocardial
  edema. Blood transfusions are indicated to
  optimize oxygen delivery if the hemoglobin falls
  below 10 g/dL. Mean arterial pressure should be
  maintained between 80 and 90 mm Hg. If fluid
  resuscitation is inadequate to restore blood
  pressure in the hypotensive donor, a dopamine
  infusion is initiated for inotropic support.
  Vasopressors are occasionally indicated for
  hypotension caused by loss of systemic vasomotor
  tone. Prolonged administration of high-dose
  catecholamine therapy (dopamine gt1015 µg/
  kg/min) has been associated with poor cardiac
  function in the posttransplant period because of
  depletion of myocardial norepinephrine stores.
  Traditionally, these patients were rejected for
  use as cardiac donors, but high-dose inotropic
  support is no longer an absolute contraindication
  for donation.
• Maintenance of normal temperatures, electrolyte
  levels, osmolarity, acid-base balance, and
  oxygenation is critical for optimal donor
  management. Common electrolyte disturbances
  include hypernatremia, hypokalemia,
  hypomagnesemia, and hypophosphatemia.97 Central
  diabetes insipidus develops in more than 50 of
  donors because of pituitary dysfunction, and
  massive diuresis complicates fluid and
  electrolyte management.
• A low-dose aqueous vasopressin (Pitressin)
  infusion is initiated at 0.8 to 1.0 U/h and
  titrated to keep urinary output at approximately
  100 to 200 mL/h. Alternatively, vasopressin may
  be administered periodically subcutaneously or
  intramuscularly (10 U every 4 hours).
• Standard ventilator management with endotracheal
  suctioning is essential in these vulnerable
  patients.
• Broad-spectrum antibiotic therapy with a
  cephalosporin is initiated following collection
  of blood, urine, and tracheal aspirate for
  culture.
• Brain death is associated with the depletion of a
  variety of hormones, including free
  triiodothyronine (T3), cortisol, and insulin.
  Donor pretreatment with hormone replacement
  therapy has proven to be beneficial.

12
Donor Heart Procurement

• The heart is inspected and palpated for evidence
  of cardiac disease or injury. The SVC, IVC and
  azygous vein are encircled with ties. The aorta
  is dissected from the pulmonary artery and
  isolated with tape.
• To facilitate access to the epigastrium by the
  liver procurement team, the cardiac team often
  then temporarily retires from the operating room
  table or assists with retraction.
• Once preparation for liver, pancreas, lung, and
  kidney explantation is completed, the patient is
  administered 30,000 IU of heparin intravenously.

13
OCTx donor operation
The azygous vein and SVC are ligated and divided
distal to the azygous vein leaving a long segment
of superior vena cava. The inferior vena cava
is clamped at the level of the diaphragm (if the
abdominal IVC is vented) and divided proximal to
the clamp to permit efflux of the cardioplegia.
Additional venting is achieved with transection
of the right superior pulmonary vein. The
cross-clamp is applied at the takeoff of the
innominate artery and the heart is arrested with
a single flush (500 mL) of cardioplegic solution
infused through a 14-gauge needle inserted
proximal to the cross-clamp. Rapid cooling of the
heart is achieved with copious amounts of cold
saline and cold saline slush. The apex of the
heart is elevated cephalad and the pulmonary
veins are divided. This maneuver is appropriately
modified to retain adequate left atrial cuffs for
both lungs and the heart if the lungs also are
being procured. While applying caudal traction
to the heart with the non-dominant hand, the
ascending aorta is transected proximal to the
innominate artery and the pulmonary arteries are
divided distal to bifurcation (modification is
necessary if the lungs are being procured).
More generous segments of the great vessels and
superior vena cava may be required for recipients
with congenital heart disease.
14
Donor heart for OCTx
Donor heart is removed from the transport cooler
and placed in a basin of cold saline. Preparation
of the donor heart is accomplished.
Electrocautery and sharp dissection are used to
separate the aorta and pulmonary artery. The
left atrium is incised by connecting the
pulmonary vein orifices and excess atrial tissue
is trimmed forming a circular cuff tailored to
the size of the recipient left atrial remnant.
15
Organ preservation OCTx

• Safe ischaemic period is around 4 to 6 hours,
  beyond this marginal donors.
• Postoperative myocardial dysfunction is secondary
  to suboptimal donor management, hypothermia,
  ischemia-reperfusion injury, and depletion of
  energy stores.
• A single flush of a cardioplegic or preservative
  solution followed by static hypothermic storage.
• No single preservation regimen has demonstrated
  consistent, clinically significant superior
  myocardial protection when used within the
  current safe limits of ischemia.
• Controversy surrounds optimal storage
  temperature, composition of cardioplegic and
  storage solutions, techniques of solution
  delivery, additives, and reperfusion
  modification.
• Hypothermia remains the cornerstone of organ
  preservation. The ideal storage temperature is
  unknown, but most institutions aim for
  temperatures between 4C and 10C.
• Crystalloid solutions of widely different
  compositions are available and the debate over
  them speaks for the fact that no ideal solution
  currently exists. Depending on their ionic
  composition, solutions are classified as
  intracellular or extracellular.
• Intracellular solutions, characterized by
  moderate to high concentrations of potassium and
  low concentrations of sodium, purportedly reduce
  hypothermia-induced cellular edema by mimicking
  the intracellular milieu. Commonly used examples
  of these solutions include University of
  Wisconsin, Euro-Collins, and in Europe,
  Bretschneider (HTK) solutions.
• Extracellular solutions, characterized by low to
  moderate potassium and high sodium
  concentrations, avoid the theoretical potential
  for cellular damage and increased vascular
  resistance associated with hyperkalemic
  solutions. Stanford, Hopkins, and St. Thomas
  Hospital solutions are representative
  extracellular cardioplegic solutions.

16
Organ preservation OCTx

• Additives for cardioplegic storage solutions
• The greatest potential for future routine use may
  lie with impermeants, substrates, and
  antioxidants.
• Impermeants (mannitol, lactobionate, raffinose,
  and histidine) counteract intracellular osmotic
  pressure to reduce hypothermia-induced cellular
  edema in the allograft.
• The preservation of myocardial high-energy
  phosphates during ischemia (to prevent
  contracture bands) and their rapid regeneration
  at reperfusion (to fuel the newly contracting
  heart) are the primary objectives for the use of
  substrate-enhanced media. Adenosine, L-pyruvate,
  and L-glutamate have been studied most intensely.
  
• Recognizing that oxygen-derived free radicals and
  neutrophils likely are critical mediators of
  myocardial reperfusion injury, considerable
  investigative effort has been undertaken to
  modify the untoward effects of ischaemia-reperfusi
  on with antioxidant additives including
  allopurinol, glutathione, superoxide dismutase,
  catalase, mannitol, and histidine.
• A variety of pharmacologic and mechanical
  strategies for leukocyte inhibition and depletion
  are also being explored.
• Benefits of continuous perfusion preservation
  techniques are currently overshadowed by
  exacerbation of extracellular cardiac edema and
  logistical problems inherent to a complex
  perfusion apparatus.
• Experimental low-pressure (microperfusion) and
  intermittent flush techniques theoretically
  provide sufficient oxygen and substrates for
  basal metabolic demands without causing
  significant edema.
• 20 of peri-operative deaths are still caused by
  cardiac dysfunction.

17
OCTx vs HCTx

• Orthotopic cardiac transplantation replacement
  of part (or occasionally all) of the recipient's
  heart with a healthy donor allograft.
• Heterotopic cardiac transplantation, the
  piggy-backing of an allograft onto the patient's
  heart, is rarely performed today. Indicated if
  orthotopic transplantation is not possible
  because of elevated pulmonary vascular resistance
  or when a donor heart is too small to sustain the
  recipient. Results are not equivalent to
  orthotopic transplant.

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OCTx ANAESTHETIC MANAGEMENT

• Once donor team has given go-ahead, recipient
  induction commences. High-dose narcotics (e.g.
  fentanyl) usually are employed for induction and
  maintenance anaesthesia.
• In light of the poor ventricular function of the
  recipient, all anesthetic agents should be
  titrated carefully with inotropic and vasoactive
  agents readily accessible for the rapid
  management of induction-induced hypotension.
  Inhaled agents may be added if necessary, but
  their potential myocardial depressant effects
  limit widespread use in this patient population.
• Prior to skin incision, some centers initiate
  aprotinin or aminocaproic acid therapy to
  minimize perioperative blood loss.

19
OCTx OPERATIVE RECIPIENT PREPARATION

• Median sternotomy and vertical pericardiotomy,
  the patient is heparinized and prepared for
  cardiopulmonary bypass. Bicaval venous
  cannulation and distal ascending aortic
  cannulation just proximal to the origin of the
  innominate artery is optimal. Umbilical tape
  snares are passed around the superior and
  inferior vena cava. Bypass is initiated, the
  patient is cooled to 28C, caval snares are
  tightened, and the ascending aorta is
  cross-clamped. The great vessels are transected
  above the semilunar commissures, whereas the
  atria are incised along the atrioventricular
  grooves leaving cuffs for allograft implantation.
  Removal of the atrial appendages reduces the risk
  of postoperative thrombus formation.
• Following cardiectomy, the proximal 1 to 2 cm of
  aorta and pulmonary artery are separated from one
  another with electrocautery, taking care to avoid
  injuring the right pulmonary artery. Continuous
  aspiration of pulmonary venous return from
  bronchial collaterals is achieved by insertion of
  a vent into the left atrial remnant, either
  directly or via the right superior pulmonary
  vein.
• Timing of donor and recipient cardiectomies is
  critical to minimize allograft ischaemic time and
  recipient bypass time. Frequent communication
  between the procurement and transplant teams
  permits optimal coordination of the procedures.
  Ideally, the recipient cardiectomy is completed
  just prior to the arrival of the cardiac
  allograft.

20
OCTx implantation
A double-ended 3-0 Prolene is taken through the
recipient left atrial cuff at the level of the
left superior pulmonary vein and then through the
donor left atrial cuff near the base of the
atrial appendage. The allograft is lowered into
the recipient mediastinum atop a cold sponge to
insulate it from direct thermal transfer from
adjacent thoracic structures. The suture is
continued in a running fashion caudally and then
medially to the inferior aspect of the
interatrial septum. Upon completion of the
posterior left atrial suture line, continuous
topical cold saline irrigation of the pericardial
well is initiated, and the patient is oriented in
a left side downhead up position to allow
drainage of the saline away from the operative
field and maximal cold saline exposure of the
left and right ventricles. .
21
OCTx implantation
22
OCTx implantation

• The second arm of the suture is run along the
  roof of the left atrium and down the interatrial
  septum. It is important to continually assess
  size discrepancy between donor and recipient
  atria so that appropriate plication of excess
  tissue may be performed.
• The left atrium is filled with saline and the two
  arms of suture are tied together on the outside
  of the heart. Some centers introduce a line into
  the left atrial appendage for continuous
  endocardial cooling of the allograft (5075
  mL/min) and evacuation of intracardiac air Left
  atrial anastomosis is complete, a curvilinear
  incision is made from the IVC toward the RA
  appendage of the allograft. This reduces the risk
  of injury to the sinoatrial node and accounts for
  the preservation of sinus rhythm observed in most
  recipients.
• The tricuspid apparatus and interatrial septum
  are inspected. Recipients are predisposed to
  increased right-sided heart pressures in the
  early postoperative period owing to preexisting
  pulmonary hypertension and volume overload. Both
  conditions are poorly tolerated by the recovering
  right ventricle.
• To avoid refractory arterial desaturation
  associated with right-to-left shunting, patent
  foramen ovale is oversewn.

23
OCTx implantation
RA anastomosis is performed in a running fashion
similar to the left with the initial anchor
suture placed either at the most superior or
inferior aspect of the interatrial septum so that
the ends of the suture meet in the middle of the
anterolateral wall. The end-to-end pulmonary
artery anastomosis is next performed using a 4-0
Prolene suture beginning with the posterior wall
from inside of the vessel and then completing the
anterior wall from the outside. It is crucial
that the pulmonary artery ends be trimmed to
eliminate any redundancy in the vessel that might
cause kinking.
24
OCTx implantation

• Rewarming is initiated at this time. Finally, the
  aortic anastomosis is performed using a technique
  similar to the pulmonary artery except that some
  redundancy is desirable in the aorta as it
  facilitates visualization of the posterior suture
  line.
• Rewarming is usually begun prior to the aortic
  anastomosis, which is performed in a standard
  end-to-end fashion.
• Routine de-airing techniques are then employed.
• Cold saline lavage is discontinued, lidocaine
  (100200 mg IV) is administered, and the aortic
  cross-clamp is removed. Half of patients require
  electrical defibrillation.
• A needle vent is inserted in the ascending aorta
  for final de-airing with the patient in steep
  Trendelenburg.
• Inotrope infusion is initiated and titrated to
  achieve a heart rate between 90 and 110 bpm.
  Temporary epicardial pacing wires are placed in
  the donor right atrium and ventricle.
• The patient is weaned from cardiopulmonary bypass
  and the cannulae are removed.

25
Anatomy

• Recent trend bicaval anastomoses rather than
  right atrial anastomoses in an attempt to
  decrease the incidence of postoperative tricuspid
  insufficiency.
• In the transplantation process, the sinoatrial
  nodes of the donor and recipient remain intact,
  and both are present within the recipient. For
  approximately 3 weeks after surgery, the
  electrocardiogram demonstrates 2 P waves
  however, the heart rate and electrical activity
  of the new heart are purely dependent on the
  intrinsic electrical system of the heart and not
  on the neurological input from the recipient.

26
ALTERNATIVE TECHNIQUES FOR ORTHOTOPIC HEART
TRANSPLANTATION

• Two alternative techniques for orthotopic heart
  transplantation have been gaining popularity over
  the past several years
• total heart transplantation involves complete
  excision of the recipient heart with bicaval
  end-to-end anastomoses
• bilateral pulmonary venous anastomoses.
• The Wythenshawe bicaval technique is performed in
  a similar fashion except that the recipient left
  atrium is prepared as a single cuff with all four
  pulmonary vein orifices. Although these
  procedures are more technically difficult than
  standard orthotopic transplantation, series using
  these techniques have reported shorter hospital
  stays and reduced postoperative dependence on
  diuretics, in addition to lower incidences of
  atrial dysrhythmias, conduction disturbances,
  mitral and tricuspid valve incompetence, and
  right ventricular failure.
• Furthermore, a recently completed randomized
  study comparing bi-atrial versus bicaval
  transplant showed an improved twelve month
  survival in the bicaval group. Long term outcomes
  and additional randomized studies evaluating
  these alternative techniques are still needed

27
RECIPIENTS WITH CONGENITAL ANOMALIES

• Unlike children and infants, transplantation in
  adults with previous palliative procedures for
  congenital anomalies is uncommon.
• Generous donor cardiectomy be performed so that
  sufficient tissue is available for optimal
  reconstruction. There are a variety of
  anomaly-specific implantation techniques.

28

• Heterotopic Heart Transplantation
• Pulmonary hypertension and right heart failure
  has remained one of the leading causes of death
  in cardiac transplantation. This has led to an
  interest in heterotopic heart tranplantation.
  Currently, heterotopic heart transplants are
  indicated in patients with irreversible pulmonary
  hypertension or significant donor-recipient size
  mismatch.
• DONOR ALLOGRAFT PREPARATION
• Like the cardiectomy for patients with
  congenital disease, the maximal length of aorta,
  superior vena cava, and pulmonary arteries is
  procured. The inferior vena cava and the right
  pulmonary veins are oversewn, and a common left
  pulmonary vein orifice is created. A linear
  incision is made along the long axis of the
  posterior right atrium extending 3 to 4 cm into
  the superior vena cava.
• Domino Donor Procedure
• The Domino donor procedure was used to avoid
  wasting relatively healthy hearts from selected
  heart-lung transplant recipients. These organs
  were transplanted into a different recipient
  using standard orthotopic or heterotopic
  techniques.

29
Heterotopic CTx
The sequence of anastomoses is as following
donor left pulmonary vein orifice to recipient
left atrium, donor superior vena cava-right
atrial orifice to recipient right atrium,
end-to-side aortic-aortic anastomosis, and
finally an end-to-side anastomosis joining the
pulmonary arteries of donor and recipient. By
employing this technique, the strengths of both
the native and transplanted heart are utilized.
The conserved recipient's right ventricle
provides the necessary assistance to the
transplanted heart to overcome significant
pulmonary hypertension.
30

• The incidence of tricuspid regurgitation is
  reported to be as high as 47-98 following heart
  transplantation (Chan, 2001).
• Some centers have now begun to prophylactically
  perform tricuspid annuloplasty on donor grafts
  before performing the transplantation (McGee,
  2004).

31
POSTOPERATIVE MANAGEMENT

• Because of denervation the SA node of the
  transplanted heart fires at its increased
  intrinsic resting rate of 90 to 110 bpm. The
  allograft relies on distant noncardiac sites as
  its source for catecholamines thus, its response
  to stress (e.g. hypovolemia, hypoxia, anemia) is
  somewhat delayed until circulating catecholamines
  can exert their positive chronotropic effect on
  the heart. Careful examination of the
  electrocardiogram occasionally may reveal a
  distinct P wave originating from the innervated
  atrial remnant of the recipient, and an increase
  in its rate may be used as an early indicator of
  stress. The absence of a normal reflex
  tachycardia in response to venous pooling
  accounts for the frequency of orthostatic
  hypotension in transplant patients.
• Denervation alters the heart's response to
  therapeutic interventions that act directly
  through the cardiac autonomic nervous system.
  Carotid sinus massage, Valsalva maneuver, and
  atropine have no effect on sinoatrial node firing
  or atrioventricular conduction. Because of
  depletion of myocardial catecholamine stores
  associated with prolonged inotropic support of
  the donor, the allograft often requires high
  doses of catecholamines.
• ROUTINE HEMODYNAMIC MANAGEMENT
• Donor myocardial performance is transiently
  depressed in the immediate postoperative period.
  Allograft injury associated with donor
  hemodynamic instability and the hypothermic,
  ischemic insult of preservation contribute to the
  reduced ventricular compliance and contractility
  characteristics of the newly transplanted heart.
  Abnormal atrial dynamics owing to the midatrial
  anastomosis exacerbate the reduction in
  ventricular diastolic loading. An infusion of
  epinephrine or dobutamine is initiated routinely
  in the operating room to provide temporary
  inotropic support. Restoration of normal
  myocardial function usually permits the cautious
  weaning of inotropic support within 2 to 4 days.
• EARLY ALLOGRAFT FAILURE
• Early cardiac failure accounts for up to 25 of
  perioperative deaths of transplant recipients.
  The cause may be multifactorial, but the most
  important etiologies are pulmonary hypertension,
  ischemic injury during preservation, and acute
  rejection. Mechanical support with an
  intra-aortic balloon pump or ventricular assist
  device is indicated in cases refractory to
  pharmacologic interventions. Re-transplantation
  in this setting is associated with very high
  mortality.
• Chronic left ventricular failure frequently is
  associated with elevated pulmonary vascular
  resistance, and the unprepared donor right
  ventricle may be unable to overcome this
  increased afterload. Although recipients are
  screened to ensure that those with irreversible
  pulmonary hypertension are not considered for
  transplantation, right heart failure remains a
  leading cause of early mortality. Initial
  management involves employing pulmonary
  vasodilators such as inhaled nitric oxide,
  nitroglycerin, or sodium nitroprusside. Pulmonary
  hypertension refractory to these vasodilators
  will often respond to prostaglandin E1 (PGE1).
  Inhalation nitric oxide is considered the
  standard at several institutions. Intra-aortic or
  pulmonary artery balloon counterpulsation and
  right ventricular assist devices have been
  utilized in patients unresponsive to medical
  therapy.
• DYSRHYTHMIAS
• Sinus or junctional bradycardia occurs in more
  than half of transplant recipients. The primary
  risk factor for sinus node dysfunction is
  prolonged organ ischemia. Adequate heart rate is
  achieved with inotropic drug infusions and/or
  temporary epicardial pacing. Most
  bradyarrhythmias resolve over 1 to 2 weeks,
  although recovery may be further delayed in
  patients who received preoperative amiodarone
  therapy. Theophylline has been effective in
  patients with bradyarrhythmias and has decreased
  the need for permanent pacemakers in this patient
  population. Ventricular arrhythmias, primarily
  premature ventricular beats (PVCs) and
  nonsustained ventricular tachycardia, have been
  reported in up to 60 of recipients when
  monitored continuously. AF/flutter is treated
  with digoxin, but at a higher dose than used in
  the setting of an innervated heart. Arrhythmias
  occasionally are markers for acute rejection.
• SYSTEMIC HYPERTENSION
• Mean arterial pressures greater than 80 mm Hg
  should be treated to prevent unnecessary
  afterload stress on the allograft. In the early
  postoperative period, intravenous sodium
  nitroprusside or nitroglycerin is administered.
  Nitroglycerin is associated with less pulmonary
  shunting because of a relative preservation of
  the pulmonary hypoxic vasoconstrictor reflex. If
  hypertension persists, an oral antihypertensive
  can be added to permit weaning of the parenteral
  agents.

32

• Respiratory Management
• The respiratory management is the same as
  following routine cardiac surgery.
• Renal Function
• Preoperative renal insufficiency owing to
  chronic heart failure and the nephrotoxic effects
  of cyclosporine places the recipient at increased
  risk of renal insufficiency. Acute
  cyclosporine-induced renal insufficiency usually
  will resolve with the reduction in cyclosporine
  dose. Patients at risk for renal failure
  initially may receive cyclosporine as a
  continuous intravenous infusion to eliminate the
  wide fluctuations in levels associated with oral
  dosing. Furthermore, concurrent administration of
  mannitol with cyclosporine may reduce its
  nephrotoxicity. Alternatively, some centers
  administer a cytolytic agent in the immediate
  postoperative period and delay the initiation of
  cyclosporine therapy.
• Intermediate Care Unit and Convalescent Ward
• The increasing risk of nosocomial infections
  with resistant organisms has led to shorter
  hospital stays for cardiac transplant recipients.
  Most patients are discharged 7 to 14 days
  following transplantation. Patient education is
  performed by the cardiac nursing staff. Topics
  include medications (regimens and potential side
  effects), diet, exercise (routines and
  restrictions), and infection recognition.
• Outpatient Follow-up
• Close follow-up by an experienced transplant
  team is the cornerstone for successful long-term
  survival after cardiac transplantation. This
  comprehensive team facilitates the early
  detection of rejection, opportunistic infections,
  patient noncompliance, and adverse sequelae of
  immunosuppression. Clinic visits routinely are
  scheduled concurrently with endomyocardial
  biopsies and include physical examination, a
  variety of laboratory studies, CXR and ECG.

33
IMMUNOSUPPRESSIVE THERAPY

• An organism's ability to distinguish self from
  non-self is critical for its survival in a
  hostile environment. In transplantation, the
  recipient's host defense mechanisms recognize the
  human leukocyte antigens (HLA) on allograft cells
  as being non-self and, if permitted, will respond
  to eradicate the foreign cells.
• The ultimate goal of immunosuppressive therapy is
  the selective modulation of the recipient's
  immune response to prevent rejection, whilst
  sparing immune defenses against infections or
  neoplasia and minimizing the toxicity associated
  with immunosuppressive agents

34
Pharmacologic Immunosuppressive Strategies

• Early induction phase followed by a long-term
  maintenance phase. This basic strategy
  essentially is universal, although the choice of
  immunosuppressive agents, dosages, and
  combination protocols vary among transplantation
  centers.
• Tendency for allograft rejection is greatest in
  the early postoperative period the most intense
  immunosuppression is administered during this
  induction phase. Most programs employ a triple
  immunosuppressive regimen while some centers also
  provide additional induction prophylaxis with
  potent polyclonal antibodies, and OKT3 or IL-2
  blockers.
• After several months, immunosuppression and
  rejection surveillance are gradually reduced to
  chronic maintenance phase levels and frequencies.
  
• Most centers use triple drug therapy
  cyclosporine, steroids, and mycophenolate
  mofentil or azathioprine. The use of a multidrug
  regimen permits adequate immunosuppression with
  reduced doses of individual agents to minimize
  their toxicity. The use of cyclosporine has
  allowed for steroid-free maintenance
  immunosuppression, thus avoiding the multiple
  untoward sequelae associated with chronic
  corticosteroid therapy immunosuppression.The
  timing of steroid withdrawal varies as some
  clinicians discontinue prednisone within several
  weeks of transplantation, whereas others delay
  the taper until 6 to 12 months posttransplantation
  .
• Recently, it has been suggested that the majority
  of patients can be completely tapered off
  steroids without an increased incidence of
  rejection. Attempts at corticosteroid withdrawal
  in patients with history of rejection, however,
  have usually been unsuccessful.

35
Hyperacute Rejection

• Results from pre-formed, donor-specific
  antibodies in the recipient. ABO blood group and
  panel reactive antibody screening have made this
  condition a rare complication.
• The onset of hyperacute rejection occurs within
  minutes to several hours after transplantation
  and the results are catastrophic.
• Gross inspection reveals a mottled or dark red,
  flaccid allograft, and histologic examination
  confirms the characteristic global interstitial
  hemorrhage and edema without lymphocytic
  infiltrate.
• Immunofluorescence techniques reveal deposits of
  immunoglobulins and complement on the vascular
  endothelium.
• No treatment is effective except
  retransplantation, and even this aggressive
  strategy frequently is unsuccessful.

36
Complications

• Bleeding from the suture lines is a rare
  occurrence but may require reexploration.
• Hyperacute rejection can occur immediately after
  blood flow is restored to the allograft and up to
  1 week after surgery despite therapeutic
  immunosuppression.
• Infection is the primary concern. Preventive
  measures should be instituted. Early on bacterial
  and fungal infections. Fungal infections can
  appear if the patient is diabetic or
  overimmunosuppressed. Prophylaxis for
  Pneumocystis carinii is universally administered,
  as is therapy for CMV infection. Maintain
  vigilance for other uncommon infectious processes
  including Listeria, Legionella, Chlamydia, and
  Nocardia infections.
• Psychiatric disturbances from steroid therapy can
  occur in the immediate posttransplant period.
  These disturbances may be predicted from the
  pre-transplantation psychiatric evaluation and
  thus averted.
• Cardiac rejection is to be expected and should be
  detected by endomyocardial biopsy. Depending upon
  the severity of the incident, the process can be
  treated with steroid therapy alone, polyclonal
  antibody therapy, or monoclonal antibody therapy.
  
• Allograft vascular disease is the main cause of
  late graft failure and death. The coronary
  arteries develop a progressive concentric
  myointimal hyperplasia. This hyperplasia can
  develop as early as 3 months after
  transplantation. The cause of the process is
  unclear. However, CMV infection and recurrent
  rejection episodes are thought to be associated
  with the cause. Current research indicates that
  the initial ischemia/reperfusion injury of the
  allograft coupled with repeated rejection
  episodes might contribute to the process. The
  only available therapy is re-transplantation. The
  process can sometimes be treated by stenting of
  the diseased vessels.

37
CHRONIC COMPLICATIONS

• Allograft Coronary Artery Disease
• Long-term survival of cardiac transplant
  recipients is primarily limited by the
  development of allograft coronary artery disease
  (ACAD), the leading cause of death after the
  first posttransplantation year.343345
  Angiographically detectable ACAD is reported in
  approximately 50 of patients by 5 years after
  transplantation. The etiology of this allograft
  vasculopathy is multifactorial and involves both
  immunologic and nonimmunologic components.
  Recently, it has been shown that immune-related
  risk factors appear to be more significant in the
  development of ACAD.346348 Likewise, many
  nonimmune-associated related risks have been
  implicated in ACAD including increased donor age,
  hyperlipidemia, and CMV infection.349352 These
  immune and nonimmune risk factors lead to unique
  coronary pathology characterized by diffuse,
  concentric intimal proliferation with
  infiltration by smooth muscle cells and
  macrophages leading to narrowing along the entire
  length of the vessel.353354 Furthermore,
  collateral vessels are notably absent. ACAD may
  begin within several weeks posttransplantation
  and insidiously progress at an accelerated rate
  to complete obliteration of the coronary lumen
  with allograft failure secondary to ischemia.355
• The clinical diagnosis of ACAD is difficult and
  complicated by allograft denervation resulting in
  silent myocardial ischemia. Ventricular
  arrhythmias, congestive heart failure, and sudden
  death are commonly the initial presentation of
  significant ACAD. Noninvasive screening tests
  (e.g., thallium scintigraphy) are unreliable in
  transplant recipients.356 Annual coronary
  angiogram is the current gold standard for ACAD
  surveillance. However, due to the previously
  mentioned pathological changes, it underestimates
  the extent of disease and is insensitive to early
  atherosclerotic lesions.357 This has led to
  growing interest in intravascular ultrasound
  (IVUS) devices.
• IVUS is better equipped to provide important
  quantitative information regarding vessel wall
  morphology and the degree of intimal
  thickening.358359 Some centers have begun to use
  IVUS for the early detection of ACAD however,
  concerns have been raised concerning its ability
  to assess more long-term lesions.360 Currently,
  the only definitive treatment for advanced ACAD
  is retransplantation due to the diffuse and
  distal nature of ACAD. Based on this lack of
  effective treatment options, an emphasis has been
  placed on prevention of ACAD. Currently,
  prophylactic management focuses on empiric risk
  factor modification (dietary and pharmacologic
  reduction of serum cholesterol, cessation of
  smoking, hypertension control, etc.). Several
  studies have demonstrated a decrease in ACAD in
  patients treated with a calcium channel blocker
  or HMG-CoA reductase inhibitors.348,361
• Renal Dysfunction
• Irreversible interstitial fibrosis caused by
  cyclosporine nephrotoxicity is chiefly
  responsible for the chronic renal dysfunction
  observed in cardiac transplant recipients.362363
  Its pathogenesis is unclear but is believed to be
  secondary to afferent arteriolar vasoconstriction
  with secondary ischemia.364365 Direct tubular
  toxicity also may play a contributory role.366
  Most renal injury occurs during the first 6
  months following transplantation concurrent with
  the highest levels of cyclosporine. Little
  additional decline in renal function occurs after
  1 year.367 Frequent monitoring of cyclosporine
  levels and avoidance of intravascular volume
  depletion are important preventive measures.368
  Approximately 3 to10 of patients develop
  end-stage renal failure requiring dialysis or
  renal transplantation.369
• Hypertension
• Moderate to severe systemic hypertension afflicts
  50 to 90 of cardiac transplant recipients and
  is a difficult problem to manage. Peripheral
  vasoconstriction in combination with fluid
  retention seem to play the greatest role.
  Although the exact mechanisms are unclear, it
  likely involves a combination of
  cyclosporine-induced tubular nephrotoxicity and
  vasoconstriction of renal and systemic arterioles
  mediated by sympathetic neural activation. No
  single class of antihypertensive agents has
  proven uniformly effective, and treatment of this
  refractory hypertension remains empiric and
  difficult.
• Malignancy
• Chronic immunosuppression is associated with an
  increased incidence of malignancy. The estimated
  risk of carcinoma is almost 100-fold greater than
  in the general population
• Lymphoproliferative disorders and carcinoma of
  the skin are most common. The risk of these
  malignancies is increased further following
  monoclonal and polyclonal antibody therapy There
  is a predilection for unusual extranodal
  locations (e.g., lung, bowel, and brain).
  Treatment options in transplantation include a
  reduction in immunosuppression and high-dose
  acyclovir (to attenuate EBV replication) in
  addition to conventional therapies for carcinoma
  (chemotherapy, radiation therapy, and surgical
  resection).
• Other
• Hyperlipidemia eventually develops in the
  majority of recipients and is managed with
  dietary restrictions, exercise, and
  lipid-lowering agents.
• Osteoporosis
• Avascular necrosis of weight-bearing joints

38
RESULTS OF OCTx

• Operative mortality 5 to 10. Primary graft
  failure is the most frequent cause of early
  death. Overall 1-year survival is approx. 80
  with a 4 mortality per year for subsequent
  years.
• Infection and rejection account for the majority
  of deaths in the first 6 months thereafter,
  accelerated coronary artery disease eventually
  claims the lives of most recipients. Risk factors
  associated with increased mortality include
  ventilator dependence, previous cardiac
  transplantation, preoperative VAD or IABP,
  recipient age greater than 65 years, female
  gender (donor or recipient), and donor age
  greater than 50 years.
• Health-related quality of life (HRQOL) in
  patients following cardiac transplantation
  demonstrates that most experience a HRQOL that
  approaches that of the normal population.
  Although cardiac reserve is reduced, exercise
  tolerance is improved dramatically compared to
  preoperative level, and recipients usually can
  enjoy an active lifestyle.
• Nevertheless, because of concerns about future
  disability, recipients often encounter
  significant problems with postoperative
  employment and health insurance coverage
  particularly if over 50 years of age.

39
CARDIAC RE-TRANSPLANTATION

• Re-transplantation accounts for fewer than 3 of
  the cardiac transplants. Primary indications
  allograft coronary artery disease and refractory
  acute rejection.
• Actuarial survival remains markedly reduced
  following re-transplantation if performed within
  6 months of the initial procedure or in the
  setting of acute rejection. Recent data suggest
  that the survival rate for cardiac
  re-transplantation at 1 year is 55.
• Recent data from the International Society for
  Heart and Lung Transplantation (ISHLT) also shows
  though that if re-transplantation occurs 2 years
  after the initial transplant procedure, the
  1-year survival rate markedly improves but
  remains approximately 4 to 6 below that of
  primary cardiac transplantation.

40
FUTURE 

• Clinical outcome of heart transplantation has
  dramatically improved. Although cardiac
  replacement remains the best therapeutic option
  for patients with end-stage heart failure, a
  number of challenges await future investigators
  to further improve survival and reduce
  transplant-related morbidity.
• A major factor limiting long-term survival of
  recipients is allograft rejection and the
  untoward effects of immunosuppression.
  Development of reliable, noninvasive diagnostic
  studies will permit more frequent evaluations for
  the early detection of rejection and for
  monitoring the effectiveness of therapy.
  Ultimately, this will allow more precise control
  of immunosuppression, and in turn a reduction in
  cumulative allograft injury and infectious
  complications.
• Immunosuppressive strategists will continue their
  efforts to establish specific unresponsiveness to
  antigens of transplanted organs in hopes of
  preserving much of the recipient's immune
  responses. Novel immunosuppressive agents and
  techniques are under continuous investigation for
  this purpose. Alternatively, donor organs may be
  made less susceptible to immunologic attack
  through genetic engineering techniques by
  altering the expression of cell membrane-bound
  molecules. This approach is being currently
  utilized in the pursuit of clinically applicable
  xenotransplant sources.
• Xenografts eventually may be an additional source
  of donor organs, although extended xenograft
  survival remains an elusive goal. Complicating
  this alternative are unresolved ethical issues
  concerning transgenic experimentation and the
  potential for transmission of veterinary
  pathogens to an immunosuppressed recipient.
• Future improvements in organ preservation
  permitting extension of the storage interval will
  have several benefits. In addition to a modest
  increase in the donor pool, extension of storage
  times would permit better allocation of organs
  with respect to donor-recipient immunologic
  matching. There is growing evidence that human
  lymphocyte antigen (HLA) matching may be
  important for long-term graft function through
  attenuation of chronic rejection. Reducing the
  ischemic injury may also result in an attenuation
  of transplant coronary artery disease.
• Mechanical assist devices are being used more
  frequently in patients with end-stage heart
  failure and may prove to be the best solution for
  the current organ shortage. Assist devices are
  being currently used both as a bridge to
  transplantation and a destination therapy. The
  Randomized Evaluation of Mechanical Assistance
  for the Treatment of Congestive Heart Failure
  (REMATCH) study demonstrated a survival benefit
  in heart failure patients in which assist devices
  were utilized versus all other forms of treatment
  for heart failure.61 It appears that as the
  technology of assist devices continues to
  improve, it is only a matter of time before they
  become a long-term solution for patients with
  severe congestive heart failure.

41
History heart-lung and lung transplantation

• First lung transplantation James Hardy 1963. But
  it took another 20 years before routine.
• First Heart-Lung transplantation Demikhov in dogs
  1962, Reitz 1981 human
• Initial graft failure secondary to
• inadequate preservation
• long ischaemic times
• lack of good immuno-suppressive drugs
• technical difficulties with bronchial anastomoses

42

• En-bloc double lung replacement introduced by
  Patterson in 1988. This technique was later
  replaced by sequential bilateral lung
  transplantation, by Pasque in 1990.
• More recent operative innovations include living
  lobar transplantation, an alternative to
  cadaveric bilateral lung transplantation.
• Combined heart-lung and isolated lung
  transplantation have emerged as lifesaving
  procedures for patients with end-stage
  cardiopulmonary or pulmonary disease.
• To date, 2861 combined heart-lung transplants,
  7204 single lung transplants, and 5420 bilateral
  lung transplants have been performed worldwide.
  While the number of heart-lung transplants
  performed annually has declined in recent years,
  the number of single and bilateral lung
  transplantation procedures remains stable.

43
(No Transcript)
44
Indications HLTx
45
Indications for single and bilateral lung
transplantation
46
Contra-indications to HLTx and LTx

• Age gt 50 (heart-lung), gt 55 (bilateral lung), gt
  60 (single lung)
• Significant systemic or multisystem disease
  (e.g., peripheral or cerebrovascular disease,
  portal hypertension, poorly controlled diabetes
  mellitus)
• Significant irreversible hepatic or renal
  dysfunction (e.g., bilirubin gt 3.0 mg/dL,
  creatinine clearance lt 50 mg/mL/min)
• Active malignancy
• Corticosteroid therapy (gt 10 mg/day)
• Panresistant respiratory flora
• Cachexia or obesity (lt 70 or gt 130 ideal body
  weight)
• Current cigarette smoking
• Psychiatric illness or history of medical
  noncompliance
• Drug or alcohol abuse
• Previous cardiothoracic surgery (considered on a
  case-by-case basis)
• Severe osteoporosis
• Prolonged mechanical ventilation
• HIV or HBsAg positivity
• Hepatitis C infection with biopsy-proven liver
  disease

47
Recipient selection HLTx and LTx

• Progressively disabling cardiopulmonary or
  pulmonary disease who still possess the capacity
  for full rehabilitation after transplantation..
• Life expectancy of less than 18 to 24 months
  despite the use of appropriate medical or
  alternative surgical strategies. On average,
  waiting times can be from 6 to 36 months.
  Unfortunately, mortality while on the waiting
  list remains nearly 20 for both lung and
  heart-lung transplant candidates.
• Disabling symptoms prompting consideration for
  transplantation typically include dyspnea,
  cyanosis, syncope, and haemoptysis. NYHA classes
  III or IV.
• Evaluation includes a complete history, physical
  examination, laboratory tests, specialized
  studies, and a psychosocial evaluation.

48
Tests and studies recipient evaluation HLTx and
LTx

• Laboratory tests and studies    routine
  haematology including clotting, blood type and
  antibody screen, Immunology panel (FANA, RF),
  UE, LFTs    Electrolytes, including Mg2     CK
  with isoenzymes    Serum protein
  electrophoresis    Urinalysis    Viral
  serologies        Compromised host panel
  (cytomegalovirus, adenovirus, varicella-zoster,
  herpes simplex, Epstein-Barr virus)        Hepatit
  is A, B, and C antibodies, hepatitis B surface
  antigen (HBsAg)        Cytomegalovirus
  (quantitative antibodies and IgM) Human
  immunodeficiency virus    Electrocardiogram    Che
  st x-rayStudies obtained as indicated    Echocardi
  ogram with bubble study    MUGA for right and
  left ventricular ejection fraction    Cardiac
  catheterization with coronary angiogram    Thoraci
  c CT scan    Quantitative ventilation-perfusion
  scans    Carotid duplex    Mammogram    Sputum
  for Gram stain, AFB smear, KOH, and routine
  bacterial, mycobacterial, and fungal cultures
• Required for listing (phase II)HLA and DR typing
• Transplant antibody
• Quantitative immunoglobulins
• Histoplasma, Coccidiodes, and Toxoplasma titers
  PPD
• Pulmonary function tests with arterial blood
  gases
• 12-hour urine collection for creatinine clearance
  and total protein
• Urine viral culture

49

• It is extremely important that a candidate's
  medical condition be optimized prior to
  heart-lung and lung transplantation. Standard
  medical measures should be aggressively employed
  by the patient's local physician, and the patient
  should have routine follow-up at the transplant
  center.
• Supplemental oxygen is recommended for any
  patient exhibiting arterial hypoxemia, defined as
  either an arterial oxygen saturation less than
  90 or an arterial Po2 less than 60 mm Hg at
  rest, during exertion, or while asleep.
• For patients with heart failure, standard
  therapeutic measures are applied, including
  dietary restrictions, diuretics, and
  vasodilators. Dietary water and salt restriction
  as well as diuretic therapy facilitate
  intravascular fluid management. However,
  particular care must be exercised when using loop
  diuretics in patients with underlying pulmonary
  disease this class of potent diuretics results
  in a metabolic alkalosis that depresses the
  effectiveness of carbon dioxide as a stimulus for
  breathing. Vasodilators result in afterload
  reduction, and have been proven to effectively
  improve functional capacity and prolong survival
  in patients suffering from severe cardiac
  failure.Commonly used vasodilators include
  nitrates, hydralazine, and angiotensin-converting
  enzyme inhibitors.
• Despite the clinical heterogeneity among patients
  with primary pulmonary hypertension, conventional
  medical therapy targets the sequelae of the
  pulmonary vascular derangements associated with
  this disease process. Supplemental oxygen therapy
  is recommended to eliminate the stimulus for
  hypoxic pulmonary vasoconstriction and secondary
  erythropoiesis, thus lessening the burden placed
  on the right side of the heart and diminishing
  the likelihood of cardiac arrhythmias. Pulmonary
  vasodilator therapy is important in the treatment
  of primary pulmonary hypertension, and includes
  the use of calcium channel blockers and
  continuous prostacyclin infusions. Because most
  standard vasodilators have potent systemic
  effects, careful dosing and follow-up is
  essential. Approximately 20 of patients with
  primary pulmonary hypertension will respond to
  calcium channel blockers, and this favorable
  response can usually be predicted by the response
  to short-acting vasodilators during cardiac
  catheterization, but response to the acute
  vasodilator challenge does not always predict the
  response to long-term prostacyclin infusion.
• Interstitial lung disease in patients awaiting
  transplantation results from a wide variety of
  diffuse inflammatory processes, such as
  sarcoidosis, asbestosis, and collagen-vascular
  diseases. Increases in pulmonary vascular
  resistance leading to right-sided heart failure
  are thought to result from interstitial
  inflammatory infiltrates that entrap and
  eventually destroy septal arterioles, reducing
  the distensibility of the remaining pulmonary
  vessels.This process, coupled with closure of
  peripheral bronchioles, results in arterial
  hypoxemia, which further aggravates pulmonary
  hypertension. Corticosteroids are the mainstay of
  treatment in this class of diseases. The adverse
  effects of steroids on airway healing are well
  established, and mandate significant dose
  reductions in anticipation of heart-lung and
  isolated lung transplantation.
• The multisystem manifestations of cystic
  fibrosis, particularly chronic bronchopulmonary
  infection, malabsorption, malnutrition, and
  diabetes mellitus, pose difficult management
  problems and require aggressive chest
  physiotherapy, antibiotics, enteral or parenteral
  nutritional supplementation, and tight serum
  glucose control.
• Certain underlying diagnoses are associated with
  increased rates of pulmonary and systemic
  thrombosis and embolization. These include
  dilated cardiomyopathy, congestive heart failure,
  and primary pulmonary hypertension, and most
  centers recommend routine prophylactic
  anticoagulation with heparin, warfarin, or
  antiplatelet agents.

50
HLTx and LTx donor selection criteria

• lt 40 (heart-lung), lt 50 (lung)
• Smoking history less than 20 pack-years
• Arterial Po2 of 140 mm Hg on an Fio2 of 40 or
  300 mm Hg on an Fio2 of 100
• Normal chest x-ray
• Sputum free of bacteria, fungus, or significant
  numbers of white blood cells on Gram and fungal
  staining
• Bronchoscopy showing absence of purulent
  secretions or signs of aspiration
• Absence of thoracic trauma
• HIV negative

51
Donor Management

• Maintenance of haemodynamic stability and
  pulmonary function. Patients suffering from acute
  brain injury are often haemodynamically unstable
  due to neurogenic shock, exc