Rejection
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The body possesses a natural defence mechanism, called the immune system, which under normal circumstances acts to protect the individual against injury due to such things as infection and trauma. The immune system will perceive the transplanted organs as ‘foreign’ material and attempt to destroy them. In order to suppress this response you will need to take certain drugs (immunosuppression) for life. The principal immunosuppressant drugs used at Harefield are Cyclosporin (Sandimmun) Azathioprine (Imuran) and Prednisolone.

We are unable to predict who will reject, how frequently and how severely, but almost all patients will experience one or more rejection episodes at some time after the operation.

ACUTE CARDIAC REJECTION

Diagnosis
It is essential to detect and treat acute rejection as early as possible, preferably before the injury is sufficient to cause symptoms to appear. For this reason you will undergo a series of routine examinations and investigations at set intervals. The tests are carried out frequently during the first six post operative months since this is when rejection occurs most commonly.

They include physical examinations, blood tests, ECG’s, echocardiograms and a heart biopsy. The heart biopsy is currently the most conclusive method for detecting rejection and may show a positive result even when all other tests are negative or equivocal. It is a simple procedure which involves removing a tiny piece of heart muscle via a cannula placed in a neck vein under a local anaesthetic. The muscle fragment is examined under a microscope for evidence of the infiltrating cells which cause rejection.

Post transplant biopsy’s
1st Month – Once a week
2 & 3rd Month – Fortnightly
4,5&6th Month – Monthly
6th Month to 1st year – Every two months
1st year onwards – every six months (if indecated)

Additional biopsies will be performed if there is any clinical evidence of rejection, and also following a course of anti rejection treatment. When you are well these investigations will be performed on an outpatient basis. There is no need to fast before a biopsy.

Children under 12 years of age will only undergo a biopsy when all the other tests for rejection are inconclusive. In most cases this will be performed under general anaesthetic.

Symptoms
As mentioned previously we aim to detect rejection episodes at the earliest possible moment, before serious damage is sustained by the transplanted heart. It may occur therefore that you are surprised to learn that your biopsy shows evidence of rejection when you are feeling perfectly well. On the other hand you may notice some changes in your condition. The worrying signs to look out for are:

sudden unexplained fatigue
diminution of exercise tolerance
shortness of breath
fluid retention (swollen ankles, feeling bloated)
‘palpitations’ -the sensation of your heart beating fast or irregularly
raised temperature

It is important that you take note of any of these symptoms and report them to us so that we can investigate further.

REJECTION LEFT UNTREATED WILL LEAD TO IRREVERSIBLE DAMAGE TO THE HEART

Treatment
This depends on the severity of the rejection, as determined by the tests, and whether or not you are clinically well.

Mild rejection may be treated as an outpatient and usually involves an injection of steroid, Methylprednisolone {Solumedrone) daily for three days which can be given by your local doctors. If there is evidence of more severe rejection you may be admitted {to Harefield) and receive treatment via a drip in addition to the steroid injection. Repeated or persistent rejection will be treated with a course of steroid tablets.

ACUTE LUNG REJECTION

Diagnosis
Acute lung rejection is detected by the surveillance of a number of physical signs and symptoms, changes in the chest x-ray and respiratory function tests, and by the examination of lung biopsies. Biopsies of the lung are taken during bronchoscopy {direct inspection of the airways under general anaesthetic), which may also be performed to elucidate the nature of a lung infection or to look at the anastomosis {join) between donor and recipient windpipes. Patients are admitted to the ward when undergoing bronchoscopy.

The schedule for other tests is similar to that for heart recipients.

All lung transplant recipients are given a personal mini spirometer (a machine to test volume and flow of air through the lungs) which must be used every day and the results recorded in the ‘blue book’. After discharge from hospital this is the most reliable method of detecting rejection and it is vital that the test is done conscientiously every day and any changes in performance reported.

Failure to do this may result in rejection being undetected for a time which will cause progressive and irreversible lung damage.

Rejection of the heart in heart/lung recipients occurs much less commonly than lung rejection. For this reason we do not routinely carry out cardiac biopsies in these patients.

Symptoms
Lung rejection may occur without you becoming aware of any abnormal symptoms. More commonly, however, you may notice any or all of the following: .sudden unexplained fatigue
diminution in exercise tolerance
shortness of breath
dry cough
raised temperature
falling spirometry values

Treatment
This is much the same as for cardiac rejection but in addition a course of steroid tablets will almost always be started following an episode of lung rejection.

Chronic Rejection
This is a loosely applied term which we use to describe certain changes in the transplanted heart or lungs that occur several months or years following transplantation. These changes, in contrast with the acute rejection described previously, tend to occur slowly causing a gradual deterioration in performance of the heart or lungs.

In the HEART there may be an insidious replacement of the normal muscle cells by fibrous tissue which causes the heart to become stiff and to contract poorly. This leads to a diminished exercise tolerance and eventually heart failure. These changes are often, but not always associated with a narrowing of the blood vessels that supply the heart, a phenomenon known as ‘accelerated coronary artery disease’ and this can be detected during angiography which is carried out at one or two year intervals.

In the LUNGS, the problem of chronic rejection seems to occur more frequently and may appear as soon as six months after the operation. It takes the form of a condition known as obliterative bronchiolitis (OB) in which the small airways of the lungs become completely blocked by fibrous tissue, leading to a progressive deterioration in the lung function. This is demonstrated by a gradual decline in spirometry values associated with increasing breathlessness.

The changes in the lungs due to chronic rejection will start before you are aware of any symptoms, and for this reason it is essential that lung transplant recipients should continue to check their spirometry values every day for life -even when you are feeling perfectly well. Failure to do this may result in rejection being undetected for a time which will cause progressive and irreversible lung damage. Chronic rejection differs from acute rejection in that the biopsies of heart or lung tissue do not show infiltration of ‘rejection cells’ as described previously, and the response to anti-rejection treatment is usually poor. If the deterioration in cardiac or lung function progresses despite intensified immunosuppression, this may eventually lead to a need for re-transplantation.

Primary Donor Dysfunction
This term means failure of the donor organ to function adequately in the absence of any obvious cause.

When the Harefield surgeons visit the donor hospital, before they consider removal of the organs they study carefully the events which preceded the brain death of the donor to see if there were any circumstances (for example drug ingestion or chest trauma) which may adversely affect the performance of the heart or lungs. They also monitor the current condition of the donor to ensure that the organs are continuing to function normally. If there is any doubt about the acceptability of the organs, the operation will be cancelled.

As the organs are removed from the donor they are rapidly cooled down and treated with special solutions which stop the heart beating and slow down the metabolism of the cells in order to minimise damage to the tissue whilst in transit.

The lungs will remain deflated and the heart motionless until they have been sewn into their new position in the recipient’s chest cavity, the blood supply has been reconnected and the temperature of the organs has been allowed to rise towards normal.

Occasionally, at this point, it becomes clear that the new heart or lungs are not functioning optimally. A prolonged period of supportive by-pass may be required whilst the blood pressure and oxygenation gradually improve. Large doses of intravenous drugs may be needed in order to wean the patient from the heart/lung machine. In most cases there is a slow gradual improvement, but occasionally there is a relentless deterioration which can either lead to re- transplantation (rarely) or death. Almost invariably under these particular circumstances, post mortem examination fails to give any clue as to the cause of the organ failure.