Closed-loop regulation of arterial pressure after acute brain death.

The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors. Closed-loop stabilization therefore has the potential of increasing availability of acceptable donor organs, and serves to indicate feasibility within less demanding patient groups. A dynamic model of nitroglycerine pharmacology, suitable for controller synthesis, was identified from an experiment involving an anesthetized pig, using a gradient-based output error method. The model was used to synthesize a robust PID controller for hypertension prevention, evaluated in a second experiment, on a second, brain dead, pig. Hypotension was simultaneously prevented using closed-loop controlled infusion of noradrenaline, by means of a previously published controller. A linear model of low order, with variable (uncertain) gain, was sufficient to describe the dynamics to be controlled. The robustly tuned PID controller utilized in the second experiment kept the MAP within a user-defined range. The system was able to prevent hypertension, exceeding a reference of 100 mmHg by more than 10%, during 98% of a 12 h experiment. This early work demonstrates feasibility of the investigated modelling and control synthesis approach, for the purpose of maintaining normotension in a porcine BD model. There remains a need to characterize individual variability, in order to ensure robust performance over the expected population.

Ex Vivo Lung Perfusion Improves the Inflammatory Signaling Profile of the Porcine Donor Lung Following Transplantation.

BACKGROUND: Primary graft dysfunction and allograft rejection represent major caveats to successful lung transplantation. Reducing inflammation in donor lungs before transplantation may improve outcomes. Evidence exists that ex vivo lung perfusion (EVLP) can alter the donor lung environment, although the mechanisms remain unclear. This study aimed to characterize the inflammatory signaling profile of the lung following standard and EVLP transplant and delineate the immediate impact on the recipient circulation. METHODS: Female recipient pigs (n = 12) were randomized to undergo left lung transplantation from male donors either using the gold standard protocol (static cold storage) or following 3 hours of EVLP. The relative phosphorylation of 44 phosphokinases and the relative expression of 35 apoptosis-related molecules were profiled within the donor lung 24 hours posttransplantation. RESULTS: A global profile of mitochondrial salvage and cell survival was observed in the EVLP lung tissue compared with lungs undergoing standard transplantation. This included increased phosphorylation of downstream prosignaling kinases, including ERK1/2 and FAK. In addition, there was upregulated expression of the antiapoptotic proteins Bcl-2, HSP-70, LIVIN, and PON2 with downregulation of apoptosis inducing mitochondrial associated molecules, including clusterin, cytochrome C, and HTRA2/OMI. In the early postoperative period, there were significantly lower levels of circulating mitochondrial DNA in recipients receiving EVLP lungs compared with a standard transplant (P = 0.016). Genomic DNA did not differ between groups, with donor DNA undetectable at all time points. CONCLUSIONS: EVLP alters the inflammatory signaling profile of the donor lung before transplantation, with a global cell survival and antiapoptotic signature.

Lung edema formation during cold perfusion: important differences between rat and porcine lung.

BACKGROUND: The aim of this study was to investigate the effect of different perfusion pressures on edema formation during cold flush perfusion with the 2 most commonly used preservation solutions in clinical lung transplantation: Euro-Collins and Perfadex solutions. METHODS: Isolated rat and porcine lungs were perfused for 3 minutes at 4 degrees C to 8 degrees C at a pressure of either 10, 15 or 20 mm Hg. Weight gain was recorded continuously. Weight gain per minute was calculated after the first phase of rapid weight gain was completed. RESULTS: In the rat model, perfusion pressure of 10 mm Hg resulted in a macro- and microscopically apparent edema, irrespective of the type of preservation solution. Perfusion pressures of 10, 15 and 20 mm Hg have weight gains of 100%, 150% and 350%, respectively, after 3 minutes of perfusion. The corresponding weight gain per minute was 18%, 31% and 84% of the initial weight. There were no statistically significant differences in weight gain between the different solutions at equal perfusion pressure. In the porcine model the flow was extremely low at 10 mm Hg and no weight gain was registered, whereas the weight gain per minute at 15 and 20 mm Hg was 1.0% and 2.1% of the initial weight. CONCLUSIONS: In porcine lungs, cold perfusion at 20 mm Hg gives minimal edema formulation, whereas in rat lungs the edema formation is deleterious, irrespective of the solution used.