For Researchers

For Researchers

Exposure of cadaveric organs to periods of ischemia, restriction in blood supply, is detrimental for organ structure and function. As cellular energy stores are depleted, this results in anaerobic metabolism and the production of waste metabolites. On reperfusion, return of blood supply, organ injury is accelerated as reactive oxygen species, amongst other metabolites, are produced. The process of ischemia reperfusion injury is recognised as being detrimental to organ function and survival. Certain organs, such as the liver, appear particularly susceptible to ischemic injury.

 

In heart beating donors research has shown, that even when HLA mismatches and ischemia times are taken into consideration, significant organ injury occurs even prior to organ procurement. A number of pathophysiological processes have been implicated in leading to this organ injury. Research, in experimental studies, has shown that a complex interaction and disturbance of the hemodynamic, hormonal, coagulatory and inflammatory pathways results in significant organ injury. In experimental models, targeting these pathways has led to improvements in organ function and outcome. Donor interventional strategies have included exploring the application of heme-oxygenase up regulators, complement inhibitors, vagal nerve stimulation, aggressive hemodynamic and hormonal resuscitation amongst others.

 

Preventing organ injury in DCD donors is a particularly challenging problem, as inevitable exposure to warm ischemia occurs during the agonal phase. Reversing the detrimental effects of warm ischemia using ex vivo perfusion and resuscitation of organs is an attractive strategy in rescuing these marginal donor organs. A European multi-centre randomised control trial recently demonstrated the utility of hypothermic ex vivo kidney machine perfusion. Other experimental work has demonstrated a role for normothermic ex vivo liver preservation and even ex-vivo lung preservation.

 

The identification of a biomarker in the donor, which can be used to predict the outcomes of transplantation, would aid transplant teams in making decisions about the suitability of organs for transplantation. In addition, this would also aid post-operative management. No marker, to date, with sufficient sensitivity or specificity has been identified with adequate predictive value.

Publications

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NHS Blood and Transplant Statistics and Clinical Audit Team.

October 2011.

 

High survival rates of kidney transplants from spousal and living unrelated donors.

Terasaki PI, Cecka JM, Gjertson DW, Takemoto S. N Engl J Med. 1995 Aug 10;333(6):333-6.

 

Effects of brain death and hemodynamic status on function and immunologic activation of the potential donor liver in the rat.

van Der Hoeven JA, Ter Horst GJ, Molema G, de Vos P, Girbes AR, Postema F, Freund RL, Wiersema J, van Schilfgaarde R, Ploeg RJ Ann Surg. 2000 Dec;232(6):804-13.

 

Hormonal changes in brain death and immune activation in the donor.

Lopau K, Mark J, Schramm L, Heidbreder E, Wanner C CTranspl Int. 2000; 13 Suppl 1:S282-5.

 

 

 

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