With surgical tools in place, increased knowledge concerning immunogenetics and alloimmunity as well as improved management of immunocompromised patients, the foundations were lain for the rapid development of the transplantation enterprise. In contrast to pre-transplant conditioning by thoracic duct drainage or total lymphoid irradiation, which were too cumbersome for routine execution among the burgeoning recipient pool, cyclosporine was a facile method to produce immunosuppression de novo after transplantation. On the one hand, clinical data confirmed the potency of cyclosporine in a variety of clinical settings. On the other hand, a pleiotropic array of side effects, particularly nephrotoxicity, beclouded the regimens, even when used in reduced doses in combination with azathioprine or together with rigorous individualization of therapy by concentration control. The advent of cyclosporine condemned conditioning by pretransplant blood transfusions and donor-recipient HLA matching to therapeutic obsolescence. However, cross-matching achieved greater significance particularly due to the development of flow cytometry methods to detect modest amounts of anti-donor antibody. Adjunctive treatments with polyclonal preparations or monoclonal antibodies were developed to provide an additional layer of security during the critical induction phase of immunosuppression and for treatment of rejection episodes refractory to high dose steroid therapy. Active immunologic investigation was stimulated by antibodies that discriminated CD4+ versus CD8+ T cells, leading to dissection of their numbers of precursors or mature elements as well as their distinct activities. The search for methods to induce, maintain and detect the state of transplantation tolerance continued. The encouraging results in clinical transplantation raised a variety of ethical concerns related to public attitudes; to retrieval, distribution, and allocation of the limited supply of deceased donor organs; the increased utilization of living persons; the opportunities for commerce; the quasi-righteous requests for organ gifts by unrelated individuals and the scant financial resources for long-term treatment with costly immunosuppression. Transplantation had now achieved its rightful place in the clinical armamentarium.

Forty years of publication of transplantation proceedings--the second decade: the cyclosporine revolution.

The present study compares the preservation of the porcine pancreas by the standard Euro-Collins solution or the cardioplegic histidine-tryptophan-ketoglutarate solution (HTK). The explanted pancreas was stored at 4 degrees C for 6 and 24 h respectively, following which organ quality was assessed in a reperfusion chamber measuring physiological and biomedical parameters. After 6 h ischaemia, the amount of lactate was significantly lower when HTK was used for protection. Other parameters like insulin release, amylase release, vascular resistance and oxygen consumption of the pancreas did not indicate a significant difference. Protection with HTK significantly improved pancreas preservation after 24 h ischaemia: lactate content in the reperfusate was lower (HTK: 64.0 +/- 7.2 mumol 50 ml-1 n = 8, v. EC: 114.2 +/- 1.7 mumol 50 ml-1, n = 6), the arteriovenous flow rate was higher (HTK: 5.7 +/- 0.91 ml min-1 v. EC: 3.0 +/- 0.26 ml min-1), and the pancreatic oxygen consumption was increased (HTK: 2.15 +/- 0.22 microliter O2 min-1 g-1 v. 0.47 +/- 0.08 microliter O2 min-1 g-1). We conclude that pancreas preservation can be improved in vitro by protection with HTK solution.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2362.1990.tb01923.x

Preservation of the porcine pancreas with HTK and Euro-Collins solution: studies in a reperfusion system.

We have prospectively studied the predictive value of three tests commonly used in transplant units (mixed lymphocyte culture, phytohemagglutinininduced transformation, and skin testing with recall antigens), and their correlation with rejection and kidney loss. Thirty-five transplant receipients provided complete data for analysis. The results of mixed lymphocyte culture reactivity, phytohemagglutinin-induced transformation, and skin reactivity to recall antigens were similar and did not predict or discriminate between the patients that had few or many rejections, nor between those that kept or lost their allografts. Nonetheless, patients with a very high mixed lymphocyte culture stimulation index (above 3) had higher morbidity and mortality than those with a nonreactive mixed lymphocyte culture. Pretransplant mixed lymphocyte culture may give more important information than nonspecific immunologic tests regarding allograft outcome.

Pretransplant predictors in renal transplantation

Pretransplant immunologic reactivity to donor lymphocytes--lack of correlation with posttransplant events.

The impact of multiple organ retrieval on renal allograft function: experience of a Canadian center.

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Pretransplant immunologic reactivity to donor lymphocytes--lack of correlation with posttransplant events.

The impact of multiple organ retrieval on renal allograft function: experience of a Canadian center.