David P. Hughes

Normothermic Perfusion: A New Paradigm for Organ Preservation

Objective:Transplantation of organs retrieved after cardiac arrest could increase the donor organ supply. However, the combination of warm ischemia and cold preservation is highly detrimental to the reperfused organ. Our objective was to maintain physiological temperature and organ function during preservation and thereby alleviate this injury and allow successful transplantation. Background Data:We have developed a liver perfusion device that maintains physiological temperature with provision of oxygen and nutrition. Reperfusion experiments suggested that this allows recovery of ischemic damage. Methods:In a pig liver transplant model, we compared the outcome following either conventional cold preservation or warm preservation. Preservation periods of 5 and 20 hours and durations of warm ischemia of 40 and 60 minutes were tested. Results:After 20 hours preservation without warm ischemia, post-transplant survival was improved (27%–86%, P = 0.026), with corresponding differences in transaminase levels and histological analysis. With the addition of 40 minutes warm ischemia, the differences were even more marked (cold vs. warm groups 0% vs. 83%, P = 0.001). However, with 60 minutes warm ischemia and 20 hours preservation, there were no survivors. Analysis of hemodynamic and liver function data during perfusion showed several factors to be predictive of posttransplant survival, including bile production, base excess, portal vein flow, and hepatocellular enzymes. Conclusions:Organ preservation by warm perfusion, maintaining physiological pressure and flow parameters, has enabled prolonged preservation and successful transplantation of both normal livers and those with substantial ischemic damage. This technique has the potential to address the shortage of organs for transplantation.

Advantages of normothermic perfusion over cold storage in liver preservation.

Background. To minimize the ischemia-reperfusion injury that occurs to the liver with the current method of preservation and transplantation, we have used an extracorporeal circuit to preserve the liver with normothermic, oxygenated, sanguineous perfusion. In this study, we directly compared preservation by the standard method of simple cold storage in University of Wisconsin (UW) solution with preservation by perfusion. Methods. Porcine livers were harvested from large white sows weighing between 30 and 50 kg by the standard procedure for human retrieval. The livers were preserved for 24 hr by either cold storage in UW solution (n=5) or by perfusion with oxygenated autologous blood at body temperature (n=5). The extracorporeal circuit used included a centrifugal pump, heat exchanger, and oxygenator. Both groups were then tested on the circuit for a 24 hr reperfusion phase, analyzing synthetic function, metabolic capacity, hemodynamics, markers of hepatocyte and reperfusion injury, and histology. Results. Livers preserved with normothermic perfusion were significantly superior (P =0.05) to cold-stored livers in terms of bile production, factor V production, glucose metabolism, and galactose clearance. Cold-stored livers showed significantly higher levels of hepatocellular enzymes in the perfusate and were found to have significantly more damage by a blinded histological scoring system. Conclusions. Normothermic sanguineous oxygenated perfusion is a superior method of preservation compared with simple cold storage in UW solution. In addition, perfusion allows the possibility to assess viability of the graft before transplantation.

High-redshift radio galaxies and quasars at submillimetre wavelengths: assessing their evolutionary status

We present new results of a study of the sub-millimetre continuum emission from a sample of 9 radio galaxies and 4 radio-quiet quasars at redshifts

A Gene for an Extended Phenotype

z = 0.75 - 4.26

Behavioral mechanisms and morphological symptoms of zombie ants dying from fungal infection

. The observations were made at 800

Hepatic steatosis and normothermic perfusion-preliminary experiments in a porcine model

\mu m

The Evolution of Invasiveness in Garden Ants

, using the single-element bolometer UKT14 on the James Clerk Maxwell Telescope (JCMT), reaching a typical r.m.s. sensitivity of

Using Deep Learning for Image-Based Plant Disease Detection

\sigma_{rms} \sim 4

Phylogenetic-based nomenclatural proposals for Ophiocordycipitaceae (Hypocreales) with new combinations in Tolypocladium.

mJy and represent some of the deepest submillimetre extragalactic measurements made to date. Three detections were achieved, of which two are secure (4C41.17, Dunlop et al. (1994) and H1413

Patterns of graft infiltration and cytokine gene expression during the first 10 days of kidney transplantation.

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