Reduced-flow ex vivo lung perfusion to rehabilitate lungs donated after circulatory death

Abstract

BACKGROUND: Current ex vivo lung perfusion (EVLP) protocols aim to achieve perfusion flows of 40% of cardiac output or more. We hypothesized that a lower target flow rate during EVLP would improve graft function and decrease inflammation of donation after circulatory death (DCD) lungs. METHODS: A porcine DCD and EVLP model was utilized. Two groups (n = 4 per group) of DCD lungs were randomized to target EVLP flows of 40% (high-flow) or 20% (low-flow) predicted cardiac output based on 100 ml/min/kg. At the completion of 4 hours of normothermic EVLP using Steen solution, left lung transplantation was performed, and lungs were monitored during 4 hours of reperfusion. RESULTS: After transplant, left lung−specific pulmonary vein partial pressure of oxygen was significantly higher in the low-flow group at 3 and 4 hours of reperfusion (3-hour: 496.0 § 87.7 mm Hg vs. 252.7 § 166.0 mm Hg, p = 0.017; 4-hour: 429.7 § 93.6 mm Hg vs. 231.5 § 178 mm Hg, p = 0.048). Compliance was significantly improved at 1 hour of reperfusion (20.8 § 9.4 ml/cm H 2 O vs. 10.2 § 3.5 ml/cm H 2 O, p = 0.022) and throughout all subsequent time points in the low-flow group. After reperfusion, lung wet-to-dry weight ratio (7.1 § 0.7 vs. 8.8 § 1.1, p = 0.040) and interleukin-1b expression (927 § 300 pg/ng protein vs. 2,070 § 874 pg/ng protein, p = 0.048) were significantly reduced in the low-flow group. CONCLUSIONS: EVLP of DCD lungs with low-flow targets of 20% predicted cardiac output improves lung function, reduces edema, and attenuates inflammation after transplant. Therefore, EVLP for lung rehabilitation should use reduced flow rates of 20% predicted cardiac output.

Two Hours of In Vivo Lung Perfusion Improves Lung Function in Sepsis-Induced Acute Respiratory Distress Syndrome

“…Using the EVLP platform of isolated lung perfusion, our group previously demonstrated that lower lung perfusion flows provide better rehabilitation. 26 This likely occurred through reduction of shear stress on the vasculature, which aided in maintaining the integrity of the endothelium and limited hydrostatic edema. Therefore, our IVLP protocol targeted a low left lung perfusion goal of 8% of cardiac output, which may also play a role in reduction of pulmonary edema.…”

Establishing an economical and widely accessible donation after circulatory death animal abattoir model for lung research using ex vivo lung perfusion

“…We however, used 20% of calculated CO, as we believe that this amount of perfusion provides the lung with ample perfusion and decreases shear stress on the endothelium. 9 Additionally, we calculated the tidal volume using 6 ml per kilogram butchered bodyweight, which does not include the weight of the skin and head of the sheep. Important to note is that we did not add perfusate nor remove metabolites, to see the unadulterated effect of EVLP on sheep lungs and the perfusate.…”

“…The protocol we presented here is similar to the original porcine EVLP protocol as established by Steen et al 8 Using 40% of the calculated living cardiac output as max flow rate, is seen in many EVLP setups. We however, used 20% of calculated CO, as we believe that this amount of perfusion provides the lung with ample perfusion and decreases shear stress on the endothelium 9 . Additionally, we calculated the tidal volume using 6 ml per kilogram butchered bodyweight, which does not include the weight of the skin and head of the sheep.…”

Expanding Donor Options for Lung Transplant: Extended Criteria, Donation After Circulatory Death, ABO Incompatibility, and Evolution of Ex Vivo Lung Perfusion

“…For example, Ali et al 121 recently demonstrated that with repeated EVLP and cold ischemic preservation, they could extend total preservation time to 3 d. Other experiments have demonstrated that EVLP time can be extended by modifying aspects of EVLP protocols such as ventilator settings, perfusate composition, perfusion flow, temperature, and supplemented nutrients. [122][123][124][125][126][127][128] If this concept of extended EVLP for prolonged graft preservation can be successfully demonstrated in clinical EVLP, it would be absolutely advantageous for broader graft sharing. Additionally, acutely damaged lungs, for example, from an active infection, aspiration, or traumatic injury, raise substantial concerns for favorable transplant outcomes and cannot be used for transplant currently.…”