Time-course of plasma inflammatory mediators in a rat model of brain death.

BACKGROUND: Brain death (BD) is a donor-associated risk factor that negatively affects transplantation outcome. The inflammation associated with BD appears to have a negative effect on organ quality. Complement activation, apoptosis, and pro-inflammatory cytokine and chemokine expression are significantly increased after BD. To better understand this process, we investigated plasma chemokine and cytokine levels for 8h after BD in a rodent model.

METHODS: Thirteen healthy adult male Sprague Dawley rats were intubated and mechanically ventilated. After induction of BD, animals were kept hemodynamically stable for 8h. A panel of immune response factors, including cytokines and chemokines, were measured immediately prior to the induction of BD and at 1, 4, and 8h after BD by multiplex analyses in 10 rats.

RESULTS: In the early phase of BD, we observed an increase in heart rate and a decrease in mean arterial pressure. Only limited fluctuations were noted in the partial pressure of O2 , O2 saturation, and HCO3 . Monocyte-/macrophage- and lymphocyte-derived mediators (IL-2, IL-4, and IFN-γ) increased steadily during the 8-hour monitoring period.

CONCLUSIONS: The increase in immune responses, particularly pro-inflammatory responses, after BD is time-dependent. Cytokines and chemokines from donors and recipients require further investigation to determine the optimal time frames for organ transplantation in rodent models and humans.