More Heart Transplant Information-Part 2

 

What is rejection, and how many kinds are there?

References:
Basic Pathology edited by V. Kumar, R. Cotran, S.L. Robbins; with illustration by James A Pertine, 6th ed.

Rejection of organ transplants is a complex immunologic phenomenon that involves cell-mediated and antibody-mediated responses, both of which are targeted on the human lymphocytes antigens in the graft.

The basis of morphology and the mechanisms involved in rejection have been classified as hyper acute, acute, and chronic.

1. Hyper acute rejection:
   • May occur within minutes or a few hours in pre-sensitised persons. It is characterised by widespread acute arteritis and arteriolitis, thrombosis of vessels, and ischemic necrosis, all of which result from reaction with pre formed humoral antibodies.
   • As a consequence of the vascular damage, the graft never becomes vascularized and it undergoes ischemic necrosis.
   • It should be noted that with the current practice of cross-matching (testing recipient for the presence of antibodies directed against donors lymphocytes), hyperacute rejection is no longer a significant clinical problem.

2. Acute rejection:
   • May occur within days of transplantation, or may appear suddenly months or even years later, after immunosuppression has been employed and terminated.
   • Acute graft rejection is a combined process in which both cellular and humoral tissue injuries play parts. In any one patient, one or the other mechanism may predominate. Histologically, humoral rejection is associated with vasculitis, whereas cellular rejection is marked by an interstitial monocular cell infiltrate.

3. Chronic rejection:
   • In this type of rejection, the endothelial cells are damaged or destroyed, but the time constants of this part of heart rejection are generally much longer. Some researchers believe that the immunologic basis for accelerated coronary artery disease may be similar to rejection.

Why do some patients suffer from infection following transplantation?

References:
John R.Pepper, Asghaz Khagani and Magdi Yacoub Journal of antimicrobial chemotherapy 1995 36 suppl. B, 23-38.
Miller, L.W., Nafted, D.C., Bourge, R.C., Kirklin J.K., Brozena S.C. Infection following cardiac transplantation, Journal of Heart Lung Transplant.
McGiffin, D.C., Bonner, J.R., Kirklin, J.K., Nafted, D.C. Patterns of infection and management in cardiac transplant, in J. Wallwork (ed) Heart and Heart-Lung Transplantation, Philadelphia WB Saunders 1989, pp. 251.

Infection is an unfavourable outcome event, which almost always is related to the immunosuppression therapy.

About 30% of patients experience an infection episode, which most commonly develops within three months of transplantation.

The most common organ infected is the lung, and in one study, when this organ was involved the mortality was 22%.

The organism most frequently causing infection after heart transplantation is the Cytomegalovirus (CMV). Overall, viruses cause about 45% of infection, and bacteria about 45%; fungi and protozoa account for the remainder.

Why do coronary arteries get damaged after heart transplantation?

References:
Michael J. Dunn, Samantha J. Crip, Marlene L. Rose, Patricia M. Taylor, Magdi Yacoub Anti-endothelial antibodies and coronary artery disease after cardiac transplantation, The Lancet vol 339: June 27, 1992.

Accelerated coronary artery disease is the third most common cause of death after heart transplantation, following behind infection and acute rejection. The disease has a multifactorial aetiology, with little agreement about the relative importance of the various risk factors. Some studies provided evidence of immune involvement in this disease, and showed anti-endothelial antibodies in patients with accelerated coronary artery disease.

Why do most patients not feel pain, despite the existence of coronary disease after heart transplant?

Most of the patients with this disease after heart transplantation fail to experience typical angina (chest pain); this may be related to the likelihood that the heart allograft (donor heart) denervated permanently.

What are the common side effects of Cyclosporin drug?

References:
Penn, I. and Brunson, M.E. Cancer after Cyclosporin therapy. Transplant. Proc. 20:85, 1988.

All of the commonly used immunosuppressive drugs increase the risk of infection complications and cancer.

Cyclosporin toxicity may result in renal failure, liver failure, high blood pressure, and neurotoxicity.

Neurotoxic reaction are manifested by a fine tremor, paresthesias and, occasionally, seizures.

Other unusual side effects include the development of Hirsutism (abnormal hairiness), observed in almost all patients who receive Cyclosporin. This effect regresses as the dosage of Cyclosporin is lowered.

What are the techniques for heart transplantation?

There are two main techniques for heart transplantation:

Heterotopic, in which the donor heart is placed parallel to the recipient's heart; and

Orthotopic, in which the patient's heart is replaced with a donor heart.

1. Heterotopic heart transplant

   References:
   C.N. Barnard and D.K.C. Cooper Third international symposium on substitution Rome, May 17, 1982 c 1984 by Grune & Stratton, Inc.

   Exploration of the possibility of using the donor heart as an accessory pump had been carried out previously in laboratory experiments, most notably by Demikhov.

   Two techniques were developed at the university of Cape Town, the first of which was a means of bypassing or supporting the left ventricle only, and the second a means of biventricular support.

   Advantages and disadvantages of heterotopic as opposed to orthotopic heart transplantation:

   Advantages

   1. The recipient heart acts as a build in heart assist during;
      1. recovery from ischemia of donor heart sustained during transplantation; sever acute rejection episodes.
   2. Recipient heart may maintain circulation after irreversible rejection while awaiting a second donor.
   3. Heterotopic transplant allows for some possible recovery of the recipient heart.
   4. Can be performed even in the presence of a high pulmonary vascular resistance.

   Disadvantages

   1. Risk of systemic emboli from clots in the poorly contracting recipient left ventricle.
   2. Continuing angina related to recipient ischemic heart muscle.
   3. Risk of infection and thrombus formation in relation to presence of the prosthetic valve in the recipient heart (this is a contraindication to heterotopic transplantation)

2. Orthotopic heart transplantation

   References:
   Cardiac Surgery second edition. John W. Kirklin, Brian G. Barratt-Boyes.

   The technique of orthotopic heart transplantation has been well established for more than 30 years, based on the first description by Lower, Stofen, and Shamway. Nevertheless anastomosis of donor to recipient atria according to this technique creates atria cavities with abnormal geometry.

   This abnormal geometry has been demonstrated to be responsible for tricuspid and mitral regurgitation and for arrhythmia's resulting from sinus node injury. The risk of atrial septal aneurysms or atrial thrombus formation is certain. Because of these problems, some surgeons proposed a more anatomic surgical technique with complete excision of the recipient atria and direct anastomosis on the left pulmonary veins, right pulmonary veins, inferior vena cava and superior vena cava. But the benefit of this procedure on clinical outcome has not been demonstrated.