Importance of left atrial pressure during ex vivo lung perfusion

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Background

Ex vivo lung perfusion (EVLP) allows for the evaluation and treatment of donor lungs before transplant. Different EVLP strategies have been described using either an open left atrium (LA) (pressure of 0 mm Hg) or closed LA (pressure of 5 mm Hg). We hypothesized that maintaining a physiologic positive LA pressure during EVLP is protective to the lung.

Methods

Pig lungs were flushed with Perfadex, retrieved and stored at 4°C for 4 hours [short cold ischemic time (CIT), n = 10] or 18 hours (prolonged CIT, n = 8). Subsequently, lungs underwent normothermic EVLP for 12 hours using either an open or closed LA technique. A linear mixed effect model was used to compare functional parameters between the 2 groups.

Results

After short CIT, 12-hour EVLP could not be completed in 4 of 5 open atrium cases due to significant pulmonary edema. Lung injury was evident in this group after 7 hours of EVLP, demonstrating an increase in pulmonary vascular resistance (p < 0.001) and peak inspiratory pressure (p = 0.001), and a decrease in lung compliance (p < 0.001) and perfusate oxygenation (p = 0.04). In contrast, in the closed atrium group, all lungs completed 12 hours of EVLP with stable functional parameters. At the end of the experiment, the wet/dry ratio (p = 0.015) and lung edema score (p = 0.02) were significantly worse in the open LA group compared with the closed LA EVLP group. Similar findings were observed in the prolonged CIT group.

Conclusion

The use of a closed atrial technique to create a controlled positive LA during EVLP leads to significantly less edema and superior lung physiology.

Section snippets

Animals

Male Yorkshire pigs (25 to 35 kg) were utilized for the experiments. All animals received care in compliance with the “Principles of Laboratory Animal Care,” formulated by the National Society for Medical Research; The Guide for the Care and Use of Laboratory Animals; and the Guide to the Care and Use of Experimental Animals, formulated by the Canadian Council on Animal Care. The animal care committee of the Toronto General Research Institute, University Health Network, approved the

Ability to complete 12 hours of perfusion

All 5 closed atrium cases successfully completed 12 hours of EVLP. In contrast, 4 of 5 cases in the open atrium group could not complete 12 hours of EVLP due to the development of massive edema and complete loss of perfusate volume from the reservoir. Most of these open atrium cases developed edema starting at 7 hours of perfusion. The perfusion times in the open group were 11, 10, 9, 12 and 11 hours, and 45 minutes (recorded as 12-hour time-point), respectively.

Pulmonary physiology

Lung function parameters were

Discussion

In this study we have demonstrated the importance of a positive LA pressure carefully regulated at a physiologic level in a closed circuit to maintain lung integrity during EVLP. The main goal of EVLP is to provide a safe platform for detailed evaluation of donor lungs and, more importantly, to provide a safe means for organ treatment and repair. Different LAP management strategies in EVLP systems have been studied previously. Petak et al13 studied the effects of pulmonary vascular pressure and

Disclosure statement

M.C., S.K. and T.W. are founders of Perfusix, Inc., and XOR Labs, Toronto. Perfusix, Inc., with United Therapeutics Corporation, will provide EVLP services on a commercial basis. The other authors have no conflicts of interest to disclose.

This research was supported by the Canadian Institutes of Health Research (OOP Grant 312227). XVIVO Perfusion (Sweden) provided the Steen Solution and EVLP circuits for this study.

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