IMPROVED OUTCOMES WITH NEGATIVE PRESSURE VENTILATION (NPV) DURING NORMOTHERMIC EX VIVO LUNG PERFUSION

Nader Aboelnazar ⁰; Sayed Himmat ⁰; Sanaz Hatami ⁰; Jayan Nagendran ⁰; Darren H. Freed ⁰; Christopher W. White ⁰

²Experimental Surgery, University of Alberta, Edmonton, AB, Canada; ³Cardiac Surgery Resident, University of Alberta, Edmonton, AB, Canada; ⁴Division of Cardiac Surgery, Mazankowski Alberta Heart Institute, Edmonton, AB, Canada

Introduction: Normothermic Ex Vivo Lung Perfusion (EVLP) has increased the rate of donor organ utilization, and increased volumes of lung transplantation at centers that have adopted the technology. Current ventilation methodology for EVLP uses Positive Pressure Ventilation (PPV) with all clinically available devices. We developed a novel ventilation system that replicates in vivo lung ventilation wherein a negative pressure is applied to the pleural surface of the lung (NPV). We hypothesize that NPV would be superior to PPV during EVLP.

Methods: A fully automated NPV EVLP platform was developed and compared to conventional (PPV) EVLP. Pig and human lungs were perfused for 12 hours and physiologic parameters, cytokine profile, bronchopleural fistula (BPF) and edema formation were analyzed. A total of 24 pigs were perfused, divided equally into 4 groups based on ventilation strategy and perfusate composition: Acellular-NPV vs. Acellular-PPV, and, Cellular-NPV vs. Cellular-PPV (Acellular: STEEN solution™ & Cellular: packed Red Blood Cells + STEEN solution™). Preliminary unutilized human lungs compared Cellular-NPV (N=2) and Cellular-PPV (N=2).

Results: Using ANOVA pairwise comparison (mean±SE), pig and human lungs showed stable trends in lung oxygenation (>400 mmHg) and physiological parameters. Cytokine analysis of the pig lungs showed significantly lower TNFa, IL-6, and IL-8 production with an NPV strategy regardless of perfusate (p<0.05). Moreover, there was a 38% lower incidence of BPF with a NPV vs. PPV strategy (p=0.02). Edema after 12 hours of EVLP for pRBCs using NPV and PPV were 15.4±2.0% and 40.6±9.0% (p<0.05); while with acellular using NPV and PPV it was 33.2±6.4% and 88.1±11.0% (p<0.05) (Figure 1), respectively. Interestingly, with human lung perfusion we found edema at 12 hours for pRBCs using NPV and PPV were -10.8±9.0% and 37.1±9.0% (p<0.05) (Figure 2), respectively.

Conclusions: Negative pressure ventilation (NPV) is potentially more beneficial compared to traditional positive pressure ventilation (PPV), with significantly less inflammation, bullae, and edema formation during extended EVLP for both perfusate groups. The value of a NPV strategy may lead to further improvements to currently available clinical EVLP platforms.

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