Mild Permissive Alkalosis Improves Outcomes in Porcine Negative Pressure Ventilation Ex-Situ Lung Perfusion.

Abstract

Background: Ex-Situ Lung Perfusion (ESLP) employs a membrane deoxygenator and mixed (N₂/O₂/CO₂) or pure sweep gas (CO₂) to target venous blood gas composition with physiologic pCO₂ and pH. Clinically, mild permissive alkalosis counteracts elevated pulmonary vascular resistance (PVR) to improve perfusion. Increased PVR and pulmonary artery pressure (PAP) during ESLP mirrors rising pro-inflammatory cytokines. Increased hydrostatic pressure worsens edema and lung function. We report improved ESLP outcomes using mild permissive alkalosis.

Methods: Twelve juvenile pig lungs underwent 12-hour Negative Pressure Ventilation (NPV)-ESLP with a physiologic pH (Control: pH 7.35-7.45, n=6) or mild permissive alkalosis (pH+: pH 7.45-7.55, n=6) by varying sweep CO₂ delivery. Three left lungs per group were transplanted and assessed over 4-hours.

Results: Five Control lungs failed on ESLP due to high PAPs, low compliance, and poor oxygenation. Repeat Controls (n=6) were performed to attain 12-hours of ESLP. There were no failures in the pH+ group. Results are pH+ vs Control. Oxygenation (PaO₂/FiO₂ 454.2 vs 438.2; P = .37) and dynamic compliance (21.38 vs 22.22 mL/cmH₂O; P = .41) were stable over 12-hour NPV-ESLP. Mean evaluation pH/pCO₂/HCO₃^- was 7.50/15.6/14.5 vs 7.41/38.7/24.7. Control lungs required repeat THAM and milrinone boluses on ESLP to prevent acidosis and treat elevated PVR; this was not necessary in the pH+ group. Weight-gain/hour was similar (1.23% vs 1.38%; P = .37). Mean left lung PF ratios 4-hours post-transplantation were 301 mmHg vs 196 mmHg (P = .11). Control TNF-⍺ and IL-6 perfusate concentrations were significantly greater.

Conclusions: Mild permissive alkalosis porcine NPV-ESLP demonstrated more reliable preservation with reduced inflammation compared to a physiologic pH strategy.