New Strategies Of Organ Donor Preconditioning In Intensive Care Medicine Involving Nerves And Messenger Substances

Due to the urgent need of grafts, new strategies are warranted to increase the pool of limited resources. Organ donor preconditioning has the goal to preserve the organ quality of even marginal donors. In particular, the failure of central regulatory mechanisms and their pathophysiological consequences should be counteracted.Optimal organ perfusion and oxygenation are considered to be the most important outcome measures, to which end vasoactive substances such as catecholamines and volume replacement therapy are used. Moreover, hormone and electrolyte imbalances and an expected increase in pro-inflammatory cytokines are treated. Based on clinical data, dopamine donor preconditioning is considered to be organ protective, but may lead to haemodynamic side effects. For this reason, a dopamine derivative without vasoactive properties could be promising. N-octanoyl dopamine, a modified dopamine, revealed to be superior to dopamine in preclinical use as far as its anti-oxidative and anti-inflammatory potency are concerned and may provide an important contribution to maintaining organ quality in the future. Another approach to inhibit inflammatory processes during the brain death process is vagus nerve stimulation by reactivating the anti-inflammatory reflex or its efferent cholinergic signalling pathway. Here, afferents send pro-inflammatory information to specific nuclei in the brain. This information is passed on to the target cells via efferents and leads to an inhibition of pro-inflammatory cytokines. It is postulated that this reflex is disturbed by brain death, thus eliminating the reflex response. The restoration of this signal pathway could be effected by vagal stimulation, thus inhibiting the formation of pro-inflammatory cytokines. Both approaches consequently represent promising options for clinical research on donor preconditioning.