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. 2017 Jan;153(1):197-204.
doi: 10.1016/j.jtcvs.2016.09.029. Epub 2016 Sep 22.

Airway pressure release ventilation during ex vivo lung perfusion attenuates injury

J Hunter Mehaffey  1 , Eric J Charles  1 , Ashish K Sharma  1 , Dustin T Money  1 , Yunge Zhao  1 , Mark H Stoler  2 , Christine L Lau  1 , Curtis G Tribble  1 , Victor E Laubach  1 , Mark E Roeser  1 , Irving L Kron  3
Affiliations

Airway pressure release ventilation during ex vivo lung perfusion attenuates injury

J Hunter Mehaffey et al. J Thorac Cardiovasc Surg. 2017 Jan.

Abstract

Objective: Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation.

Methods: Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured.

Results: Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion.

Conclusions: Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.

Keywords: APRV; EVLP; airway pressure release ventilation; ex vivo lung perfusion; ischemia reperfusion; lung injury; lung transplant.

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Conflict of interest statement

There are no financial disclosures or conflicts of interest from any of the authors.

Figures

Figure 1
Figure 1
Changes in PaO2/FiO2 ratios of the left lung over the course of the experiment. PaO2/FiO2 ratios were significantly higher in the APRV group after transplantation at both the 2-hr and 4-hr reperfusion times.
Figure 2
Figure 2
Changes in PaO2/FiO2 ratios and dynamic compliance during EVLP A. No significant differences in PaO2/FiO2 ratios during EVLP were observed between the Control and APRV groups. B. Dynamic compliance throughout the 4-hours of EVLP was similar for both groups.
Figure 3
Figure 3
Lung function and edema after transplantation. PaO2/FiO2 ratios (A) and dynamic lung compliance (B) were significantly improved in the APRV group at both 2 and 4 hours of post-transplant reperfusion. C. Pulmonary edema, as a percent weight change after 4 hours of reperfusion, was significantly reduced in the APRV group during EVLP versus Control but there was no significant difference after post-transplant reperfusion.
Figure 4
Figure 4
Lung tissue expression of pro-inflammatory cytokines in left lungs of the APRV and Control groups as well as in post-EVLP right lungs. Several cytokines (IL-6 and IL-12) were significantly elevated in the Control group but were significantly reduced in the APRV group.
Figure 5
Figure 5
Representative lung H&E histology images from the Control and APRV groups (A). Although lower in the APRV group, lung injury severity scores were not significantly different between the Control and APRV groups (B).
Figure 6
Figure 6
Representative images of immunohistochemistry staining for neutrophils in lung sections from both groups after transplantation and 4-hrs of reperfusion (A). Neutrophil counts per high-powered field (HPF) were significantly reduced in the APRV group versus Control (B).
Central Image
Central Image
APRV during EVLP improves Oxygenation post-transplant despite no difference on EVLP.
See this image and copyright information in PMC

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References

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