OBJECTIVE: The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. METHODS: Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP. ATL802, an adenosine A2B receptor antagonist, was administered to select groups. Four groups (n = 4/group) were randomized: cold preservation (Cold), cold preservation with ATL802 during reperfusion (Cold + ATL802), EVLP (EVLP), and EVLP with ATL802 during ex vivo perfusion (EVLP + ATL802). Lungs subsequently were transplanted, reperfused, and assessed by measuring dynamic lung compliance and oxygenation capacity. RESULTS: EVLP + ATL802 significantly improved dynamic lung compliance compared with EVLP (25.0 ± 1.8 vs 17.0 ± 2.4 mL/cmH2O, P = .04), and compared with cold preservation (Cold: 12.2 ± 1.3, P = .004; Cold + ATL802: 10.6 ± 2.0 mL/cmH2O, P = .002). Oxygenation capacity was highest in EVLP (440.4 ± 37.0 vs Cold: 174.0 ± 61.3 mm Hg, P = .037). No differences in oxygenation or pulmonary edema were observed between EVLP and EVLP + ATL802. A significant decrease in interleukin-12 expression in tissue and bronchoalveolar lavage was identified between groups EVLP and EVLP + ATL802, along with less neutrophil infiltration. CONCLUSIONS: Severely injured donation after circulatory death lungs subjected to 2 hours of warm ischemia are transplanted successfully after enhanced EVLP with targeted drug therapy. Increased use of lungs after uncontrolled donor cardiac death and prolonged warm ischemia may be possible and may improve transplant wait list times and mortality.
OBJECTIVE: The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. METHODS:Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP. ATL802, an adenosine A2B receptor antagonist, was administered to select groups. Four groups (n = 4/group) were randomized: cold preservation (Cold), cold preservation with ATL802 during reperfusion (Cold + ATL802), EVLP (EVLP), and EVLP with ATL802 during ex vivo perfusion (EVLP + ATL802). Lungs subsequently were transplanted, reperfused, and assessed by measuring dynamic lung compliance and oxygenation capacity. RESULTS: EVLP + ATL802 significantly improved dynamic lung compliance compared with EVLP (25.0 ± 1.8 vs 17.0 ± 2.4 mL/cmH2O, P = .04), and compared with cold preservation (Cold: 12.2 ± 1.3, P = .004; Cold + ATL802: 10.6 ± 2.0 mL/cmH2O, P = .002). Oxygenation capacity was highest in EVLP (440.4 ± 37.0 vs Cold: 174.0 ± 61.3 mm Hg, P = .037). No differences in oxygenation or pulmonary edema were observed between EVLP and EVLP + ATL802. A significant decrease in interleukin-12 expression in tissue and bronchoalveolar lavage was identified between groups EVLP and EVLP + ATL802, along with less neutrophil infiltration. CONCLUSIONS: Severely injured donation after circulatory death lungs subjected to 2 hours of warm ischemia are transplanted successfully after enhanced EVLP with targeted drug therapy. Increased use of lungs after uncontrolled donorcardiac death and prolonged warm ischemia may be possible and may improve transplant wait list times and mortality.
Keywords:
adenosine A2B receptor antagonism; donation after circulatory death; ex vivo lung perfusion; lung transplantation; porcine lung transplant model
Authors: Yunge Zhao; Damien J LaPar; John Steidle; Abbas Emaminia; Irving L Kron; Gorav Ailawadi; Joel Linden; Christine L Lau Journal: J Heart Lung Transplant Date: 2010-12 Impact factor: 10.247
Authors: G Haskó; D G Kuhel; J F Chen; M A Schwarzschild; E A Deitch; J G Mabley; A Marton; C Szabó Journal: FASEB J Date: 2000-10 Impact factor: 5.191
Authors: Farshad Anvari; Ashish K Sharma; Lucas G Fernandez; Tjasa Hranjec; Katya Ravid; Irving L Kron; Victor E Laubach Journal: J Thorac Cardiovasc Surg Date: 2010-07-24 Impact factor: 5.209
Authors: Steven M Fiser; Curtis G Tribble; Stewart M Long; Aditya K Kaza; John A Kern; David R Jones; Mark K Robbins; Irving L Kron Journal: Ann Thorac Surg Date: 2002-04 Impact factor: 4.330
Authors: Yang Zhou; Daniel J Schneider; Eva Morschl; Ling Song; Mesias Pedroza; Harry Karmouty-Quintana; Thuy Le; Chun-Xiao Sun; Michael R Blackburn Journal: J Immunol Date: 2010-12-13 Impact factor: 5.422
Authors: Ashish K Sharma; Victor E Laubach; Susan I Ramos; Yunge Zhao; George Stukenborg; Joel Linden; Irving L Kron; Zequan Yang Journal: J Thorac Cardiovasc Surg Date: 2009-11-11 Impact factor: 5.209
Authors: Marcelo Cypel; Jonathan C Yeung; Shin Hirayama; Matthew Rubacha; Stefan Fischer; Masaki Anraku; Masaaki Sato; Stephen Harwood; Andrew Pierre; Thomas K Waddell; Marc de Perrot; Mingyao Liu; Shaf Keshavjee Journal: J Heart Lung Transplant Date: 2008-12 Impact factor: 10.247
Authors: Rebecca E Cagnina; Susan I Ramos; Melissa A Marshall; Guoquan Wang; C Renea Frazier; Joel Linden Journal: Am J Physiol Lung Cell Mol Physiol Date: 2009-07-02 Impact factor: 5.464
Authors: Jared P Beller; Matthew R Byler; Dustin T Money; William Z Chancellor; Aimee Zhang; Yunge Zhao; Mark H Stoler; Adishesh K Narahari; Alexander Shannon; J Hunter Mehaffey; Curtis G Tribble; Victor E Laubach; Irving L Kron; Mark E Roeser Journal: J Heart Lung Transplant Date: 2019-09-18 Impact factor: 10.247
Authors: James H Mehaffey; Dustin Money; Eric J Charles; Sarah Schubert; Angela Fernandez Piñeros; Di Wu; Sai Vineela Bontha; Robert Hawkins; Nicholas R Teman; Victor E Laubach; Valeria R Mas; Curtis G Tribble; Daniel G Maluf; Ashish K Sharma; Zequan Yang; Irving L Kron; Mark E Roeser Journal: Ann Surg Date: 2019-06 Impact factor: 12.969
Authors: Qimeng Gao; Isabel F DeLaura; Imran J Anwar; Samuel J Kesseli; Riley Kahan; Nader Abraham; Aravind Asokan; Andrew S Barbas; Matthew G Hartwig Journal: Front Immunol Date: 2022-07-01 Impact factor: 8.786
Authors: Nikhil K Prasad; Chetan Pasrija; Tara Talaie; Alexander S Krupnick; Yunge Zhao; Christine L Lau Journal: Transplantation Date: 2021-05-01 Impact factor: 4.939
Authors: Eric J Charles; J Hunter Mehaffey; Mary E Huerter; Ashish K Sharma; Mark H Stoler; Mark E Roeser; Dustin M Walters; Curtis G Tribble; Irving L Kron; Victor E Laubach Journal: Transplant Direct Date: 2018-11-12
Authors: Jasper Iske; Christopher A Hinze; Jawad Salman; Axel Haverich; Stefan G Tullius; Fabio Ius Journal: Am J Transplant Date: 2021-08-24 Impact factor: 8.086