PubMed1997
In spite of pharmacological progress, end stage congestive heart failure is still associated with a decrease in quality and expectation of life. Heart transplantation remains the last therapeutic option for these patients. While the one year survival rate has increased over the last few years up to 84%, a major problem remains the significant lack of donors. Therefore, the criteria for the selection of candidates for cardiac transplantation have to be kept quite tight: Evidence of poor outcome without transplantation is associated with ejection fractions below 20 to 25%, cardiac indices less than 2.01/min/m2, left ventricular filling pressure above 20 mm Hg and a enddiastolic diameter of > 80 mm. There are, however, also quite important functional parameters indicating the need for heart transplantation, e.g. the maximal oxygene uptake being less than 10 ml/kg/min or below 50% of the age-appropriate value. Elevated pulmonary vascular resistance above 4 to 5 Wood units without a significant decrease during application of prostaglandin derivatives or inhalation of NO represents a contraindication for orthotopic heart transplantation; alternatively, a heterotopic transplantation can be considered. Since there is a significant shortage of suitable donor organs, the donor criteria have been broadened, e. g. the accepted donor age was increased to 60 years. Based on these extended criteria, a careful donor evaluation including cardiac history, cardiac examination, ECG and echocardiogram has to be performed. Coronary angiography in older donors is suggested, but in many cases not possible due to circumstances. Further precondition for a good graft function is a sophisticated donor management until the time of explantation. Hypovolemia and hypocalemia, hypothermia, hypoxia and rapid lost of circulating triiodothyronine (T3) have to be detected and balanced. The cardioplegic solution used might not only have an impact on the immediate postoperative performance of the graft, but also on the long term outcome, particularly with regard to graft vessel disease. There are generally two types of solutions: Those with intracellular and those with extracellular electrolyte concentrations. In addition, the potassium concentration might be of some importance. Potassium seems to damage endothelial cells and trigger subsequent immunological reactions. Therefore, high potassium concentrations in the cardioplegic solution might correlate with the incidence of graft vessel disease during the long term follow-up. The surgical technique for orthotopic heart transplantation developed at the beginning of the sixties by Lower and Shumway has been used unchanged for the last 30 years. The only alteration recently introduced is the separate direct anastomosis of the pulmonary and systemic veins in order to improve the atrial function. Until recently the commonly employed immunosuppressive strategy after heart transplantation consisted of the standard drugs cyclosporin, azathioprin and prednisolon. Some transplant-units use additionally induction therapy with antibody preparations. Many centers, however, abolished this regimen due to significant short and long term side effects. Promising new, more specific antibodies (which are chimerized or humanised) could revive the induction concept. The most thoroughly tested novel immunosuppressive agent is tacrolimus (FK506). It has been demonstrated to be 10 to 100 times more potent than cyclosporin A in in vitro and in vivo models. It binds to a different binding protein (FK-binding-protein) than cyclosporin (cyclophilin), but has a similar mechanism of action inhibiting the expression of T-cell-activator genes for certain cytokines. First non-randomised studies after heart transplantation performed at the University of Pittsburgh revealed that significantly more tacrolimus than cyclosporin patients were free of rejection. In order to confirm these observations, we performed a prospective randomised controlled clin
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