Prolonged EVLP Using OCS Lung

Abstract

Background We report the ability to extend lung preservation up to 24 hours (24H) by using autologous whole donor blood circulating within an ex vivo lung perfusion (EVLP) system. This approach facilitates donor lung reconditioning in a model of extended normothermic EVLP. We analyzed comparative responses to cellular and acellular perfusates to identify these benefits. Methods Twelve pairs of swine lungs were retrieved after cardiac arrest and studied for 24H on the Organ Care System (OCS) Lung EVLP platform. Three groups (n=4 each) were differentiated by perfusate: (1) isolated red blood cells (RBCs) (current clinical standard for OCS); (2) whole blood (WB); and (3) acellular buffered dextran-albumin solution (BDAS, analogous to STEEN solution). Results Only the RBC and WB groups met clinical standards for transplantation at 8 hours; our primary analysis at 24H focused on perfusion with WB versus RBC. The WB perfusate was superior (vs. RBC) for maintaining stability of all monitored parameters, including the following mean 24H measures: pulmonary artery pressure (6.8 vs. 9.0 mmHg), reservoir volume replacement (85 vs. 1607 mL), and PaO2:FiO2 ratio (541 vs. 223). Acellular perfusion was limited to 6 hours on the OCS system due to prohibitively high vascular resistance, edema, and worsening compliance. Conclusions The use of an autologous whole donor blood perfusate allowed 24H of preservation without functional deterioration and was superior to both RBC and BDAS for extended lung preservation in a swine model using OCS Lung. This finding represents a potentially significant advance in donor lung preservation and reconditioning.

Cellular and acellular ex vivo lung perfusion preserve functional lung ultrastructure in a large animal model: a stereological study

“…Perfusion times in clinical EVLP range from 4 to 11 h. For functional assessment of lungs after donation after circulatory death (DCD) or of marginal lungs after donation after brain death usually shorter time periods are used, while for reconditioning purposes or therapeutic interventions an extension of perfusion times up to 6–12 h or even beyond might be necessary [ 30 – 32 ]. In experimental EVLP, perfusion times of up to 24 h have been performed [ 17 , 33 ].…”

“…erythrocyte addition to perfusate. Previous studies mainly focusing on functional parameters gave differential and sometimes conflicting results regarding the superiority of any one of the techniques [ 13 – 17 ]. However, uncertainties about preferable strategies limit further expansion of EVLP usage.…”

Perfusate adsorption during ex vivo lung perfusion improves early post-transplant lung function

“…To our knowledge, EVLP for more than 12h has not been reported so far using the three widely used EVLP protocols in the clinical setting. Several studies have been performed to optimize the EVLP protocols looking at the roles of atrial pressure, 9 synchronous bronchial artery circulation, 10 cellular and acellular perfusates, 11 continued perfusate exchange, 12 negative pressure ventilation, 13 perfusate oxygen concentration, 14 continuous perfusate adsorption, 15 and positioning of donor lungs. 16 Combination of these strategies may result in prolonged EVLP times.…”

Pulmonary endothelial permeability and tissue fluid balance depend on the viscosity of the perfusion solution

“…Fluid exchange depends on the balance of hydrostatic and oncotic pressure differences between the lumen of the microvasculature and the interstitial space, and the selective permeability of the endothelium to molecules of different sizes, as described in the classic Starling hypothesis (27). The essential roles of the normal electrolyte composition, pH, nutrient, hormonal and colloid osmotic pressure of the perfusion solution in maintaining vascular function have been well characterized in the classic isolated organ preparations such as the isolated heart, lung, and kidney, and more recently in ex vivo perfusion protocols used to recondition donor lungs before transplantation (6,16,22,25,27,35). However, these isolated organ preparations develop edema after relatively brief periods (hours).…”

“…However, these isolated organ preparations develop edema after relatively brief periods (hours). To further increase the period for which isolated organs can be maintained viable, nonphysiological modifications of classic perfusion media have been introduced such as increasing concentrations of albumin and globulins substantially above normal in vivo values to increase colloid osmotic pressure, and addition of pharmacological vasodilators and oxidant scavengers (25,35). Nonetheless, development of edema after relatively restricted periods of time remains a problem (6,35).…”