Transplantation heart

Ancient mythology and biblical references mention heart transplantation, but after the initial work of Alexis Carrel in the early 1900s, dog heart transplants were performed at Mayo Clinic in 1933. The work of Norman Shumway at Stanford University, reported in 1959, led to the first human transplant by Christian Bernard in 1967 in South Africa. By the 1970s, the enthusiasm diminished due to poor survival rate after heart transplantation until the discovery of cyclosporine. 

The first combined heart-lung transplant was performed in 1981 at Stanford University. Combined heart-lung donors need to satisfy both the requirements already described separately. Combined heart-lung transplant is recommended in patients with congenital problems affecting these organs, pulmonary hypertension and/or cystic fibrosis. The recipients for the combined transplant are recommended to be less than 55 years old. Survival rates are 79, 66, and 54% at 1 month, 1 year and 3 years, respectively, after transplantation. 

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Cardiomyoplasty could gready reduce the overwhelming need for heart transplants. It might also eliminate the need for immunosuppressive dmgs. 

Artificial Hearts. Congestive heart failure (CHF) is a common cause of disabiHty and death. It is estimated that three to four million Americans suffer from this condition. Medical therapy in the form of inotropic agents, diuretics (qv), and vasofilators is commonly used to treat this disorder (see Cardiovascularagents). Cardiac transplantation has become the treatment of choice for medically intractable CHF. Although the results of heart transplantation are impressive, the number of patients who might benefit far exceeds the number of potential donors. Long-term circulatory support systems may become an alternative to transplantation (5). 

As stated at the beginning of this article, the liver is the most intensively studied animal tissue in biochemistry. In the context of the role of free radicals in human diseases, the liver is not obviously at centre stage, since heart disease and cancer are more important in the industrialized world than, for example, cirrhosis. Free-radical biochemistry of the liver will remain a fertile area of work, however, not least because so many original ideas and techniques are developed there and then applied to the study of other tissues. The increasing use of liver transplantation, following the acceptance of kidney and heart transplants as almost routine, will surely increase the interest in the study of ischaemia-reperfusion injury in... 

Occasional exercise testing is conducted in order to ascertain disease prognosis or suitability for heart transplant. Even though these tests can demonstrate improvement in heart function and therefore slowed disease progression, patient symptoms may not improve. 

Heart transplantation represents the final option for refractory, end-stage HF patients who have exhausted medical and device therapies. Heart transplantation is not a cure, but should be considered a trade between a life-threatening syndrome and the risks associated with the operation and long-term immunosuppression. Assessment of appropriate candidates includes comorbid illnesses, psychosocial behavior, available financial and social support, and patient willingness to adhere to lifelong therapy and close medical follow-up.1 Overall, the transplant recipient s quality of life may be improved, but not all patients receive this benefit. Posttransplant survival continues to improve due to advances in immunosuppression, treatment and prevention of infection, and optimal management of patient comorbidities. 

Cardiac transplantation is one option for patients with severe heart failure. Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III or IV symptoms and have an ejection fraction of less than 25%.1,3 The general indications for cardiac transplantation include rapidly declining cardiac function and a projected 1-year mortality rate of greater than 75%. Mechanical support with an implantable left ventricular assist device may be appropriate while patients await the availability of a viable organ.1,3 Some additional reasons for heart transplant include ... 

APCs, antigen-producing cells MMF, mycophenolate mofetil OKT-3, muronomab-CD3. (Adapted from Mueller XM. Drug immunosuppressive therapy for adult heart transplantation I. Immune response to allograft and mechanism of action of immunosuppressants. Ann Thorac Surg 2004 77 354-362, with permission.)... 

Horuk R, Clayberger C, Krensky AM, et al. A non-peptide functional antagonist of the CCR1 chemokine receptor is effective in rat heart transplant rejection. J Biol Chem 2001 276 4199-4204. 

The second factor that exerts control on heart rate is the release of the catecholamines, epinephrine and norepinephrine, from the adrenal medulla. Circulating catecholamines have the same effect on heart rate as direct sympathetic stimulation, which is to increase heart rate. In fact, in the intact heart, the effect of the catecholamines serves to supplement this direct effect. In a denervated heart, circulating catecholamines serve to replace the effect of direct sympathetic stimulation. In this way, patients who have had a heart transplant may still increase their heart rate during exercise. 

McLeod HL, Lin J-S, Scott EP, Pui C-H, Evans WE. Thiopurine methyltransferase activity in American white subjects and black subjects. Clin Pharmacol Ther 1994 55 15-20. McLeod HL, Miller DR, Evans WE. Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet 1993 1341 1151. 

Schutz E, Gummert J, Mohr F, Oel-lerich M. Azathioprine induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet 1993 341 436. 

Ventricular assist devices can be used in the short-term (days to several weeks) for temporary stabilization of patients awaiting an intervention to correct the underlying cardiac dysfunction. They can also be used long term (several months to years) as a bridge to heart transplantation. Permanent device implantation has recently become an option for patients who are not candidates for heart transplantation. 

Perrault LP, Malo O, Bidouard JP, Villeneuve N, Vilaine JP, Vanhoutte PM (2003) Inhibiting the NO pathway with intracoronary L-NAME infusion increases endothelial dysfunction and intimal hyperplasia after heart transplantation. J Heart Lung Transplant 22 439-451... 

D. W. (2004) Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clinical Pharmacology and Therapeutics, 76, 167-177. 

Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G. (2000). Acute heart transplant rejection due to Saint John s wort. Lancet. 355(9203) 548-49. 

HesseUnk, D. A., Van Gelder, T., Van Schaik, R. H., et al. (2004) Population pharmacokinetics of cyclosporine in kidney and heart transplant recipients and the influence of ethnicity and genetic polymorphisms in the MDR-1, CYP3A4, and CYP3A5 genes. Clin. Pharmacol. Ther. 76, 545-556. 

Shaw LM, Korecka M, De Nofrio D, Brayman KL. (2001) Pharmacokinetic, pharmacodynamic and outcome investigations as the basis for mycophenolic acid therapeutic drug monitoring in renal and heart transplant patients. Clin Biochem 34 17-22. 

The finding that the administration of 6-mercaptopurine to rabbits following exposure to bovine serum albumin prevented antibody formation [374] formed the basis for a new area of chemotherapy for purine analogues and other antimetabolites and was soon followed by the use of these drugs for the therapy of autoimmune disease and the suppression of homograft rejection. This subject has been reviewed in depth [ 12, 375, 375a], has occasioned a symposium [376], and has received much recent publicity as a result of human heart transplants. 

Despite efforts such as revascularization to halt the progression to ischemic heart failure, ventricular remodeling is still a growing danger. Efforts to treat severely failing hearts refractory to medical therapy have included heart transplantation and mechanical ventricular assistance [1]. Until recently, cardiologists believed that beyond revascularization and medical therapy, the process of ischemic heart failure was irreversible because the heart lacked the capacity to renew itself. 

Hocht-Zeisberg E, Kahnert H, Guan K, Wulf G, Hemmerlein B, Schlott T, Tenderich G, Korfer R, Raute-Kreisen, Hasenfuss G. Cellular repopulation of myocardial infarction in patients with sex-mismatched heart transplantation. Eur Heart J 2004 25 749-758. 

Owing to his tireless efforts, Brano became Associate Director of Transplant Research in 1998 and Director of the Center for Cardiac Support in 2005. In the latter capacity, he lectured and traveled extensively, sharing his knowledge and expertise about mechanical circulatory support, heart transplantation, and other heart failure therapies with colleagues and friends. 

Until his death in September 2007, Brano continued to make invaluable contributions to the field of heart transplantation, particularly immunosuppression... 

Simonson, S.G., Raza, A., Martin, P.D., Mitchell, P.D., Jarcho, J.A., Brown, C.D.A., Windass, A.S. and Schneck, D.W. (2004) Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine. Clinical Pharmacology and Therapeutics (St. Louis), 76, 167-177. 

Sebbag, L., Boucher, P., Davelu, P., Boissonnat, P., Champsaur, G., Ninet, J., Dureau, G., obadia, J.F., Vallon, J.J. and Delaye, J. (2000) Thiopurine s-methyl-transferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients. Transplantation, 69,1524—1527. 

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