Pushing the limits… again!!
Two recent studies presented at the April, 2018 ISHLT congress in Nice, both from Toronto, suggest that the safe duration of both cold preservation and warm ex-vivo perfusion of lungs (EVLP) can be further extended by relatively modest protocol modifications.
Extending warm ex-vivo lung perfusion (EVLP) to 24 hours!
Takahashi et al investigated strategies to stabilize extended EVLP in a pig model by varying the manner in which the Steen solution perfusate is partially replenished during the course of a prolonged 24-hour EVLP perfusion run.
The current EVLP protocol is reliable only up to 12 hours which limits potential advances in therapeutic and reconditioning strategies. The authors noted that the composition of Steen solution changes over time during extended EVLP and therefore investigated whether a Continuous Replacement (CR) or a modified feed (MF) strategy could be used to improve the stability of normothermic EVLP to reliably preserve lung integrity for up to 24 hours.
Pig lungs were placed in the EVLP system for 24 hours and divided into three groups: 1. Conventional Toronto EVLP (Control), 2. Continuous Replacement (CR), and 3. Modified Feed (MF). In the Control group, they added 100 mL Steen solution every 2 hours (as per their current practise). In the CR group, they continuously injected fresh Steen solution at 50 mL/hr. In the MF group, they controlled the glucose levels (>10 mmol/l) and sodium levels (<155 mmol/l) by adding 5% glucose solution and water to Steen solution calculated to maintain stable perfusate glucose and sodium levels.
In the Control group, 3 of the 4 lungs failed to complete 24 h EVLP (Perfusion times: 18, 19, 20, 24 hours). In the MF group, 3 out of 4 lungs were able to maintain stable glucose and electrolyte concentrations, and only 3 out of 4 lungs completed 24h EVLP (Perfusion times: 23, 24, 24, 24 hours). Notably, all lungs in the continuous replacement (CR) group successfully completed 24 hours EVLP. The authors conclude, “We have shown that modifications of the technique of replenishment of the perfusate can significantly improve stability of the EVLP process.”
5. Takahashi et al, Twenty-Four Hour Ex Vivo lung Perfusion: Strategies to Stabilize Extended EVLP in a Pig Model J Heart Lung Transplant. 37, 45, April 2018, Suppl S223-4 (link to abstract)
Extending cold lung preservation to 48 hours!!
A recent study from Toronto (Ali et al, 2018) suggests a novel extracellular oxygen carrier may help extend the safe duration of cold lung preservation to 36 or even 48 hours. The novel oxygen carrier, HEMO2Life, aka Hemarina-M101, is derived from hemoglobin of the lugworm or sandworm (Arenicola marina) commonly found on sandy beaches. M101 has potent anti-oxidative properties and each molecule can carry up to 156 O2 molecules.
Two groups of 4 pig lungs were statically preserved cold in either PERFADEX alone or PERFADEX + 1g/L of M101. After 36 hours of cold preservation, the lungs were evaluated by warm EVLP for another 12 hours followed by transplantation plus four hours of reperfusion.
During EVLP, lung function significantly improved in the treatment group in comparison to the control, as shown by a greater decrease in peak airway pressures, increased compliance and greater improvements in lung oxygenation. After 48 hours of preservation and four hours of reperfusion post-transplantation, the mean P/F ratio of the graft was still higher in the treatment group compared with the controls. If these results can be confirmed in a larger series this strategy may be an effective way to extend cold static lung preservation.
6. Ali A, et al, Two-Day Lung Preservation Followed by Lung Transplantation in a Large Animal Model Using Novel Extracellular Oxygen Carrier , J Heart Lung Transplant. 37, 45, April 2018, Suppl S123-4 (link to abstract)
Xvivo Insights PB-2018-05-20