BACKGROUND: Lung dysfunction after transplantation continues to be a significant clinical problem. Soluble complement receptor 1 (sCR1) is a potent inhibitor of complement activation. We evaluated the inhibitory effect of sCR1 on complement activation and reperfusion injury in pig lung allografts. METHODS: In a randomized and blinded study, left lung transplantation was performed in 13 pigs. Donor lungs were flushed and then stored for 30 hr at 4 degrees C. Control pigs (n=7) received saline, and the treatment group (n=6) received 15 mg/kg sCR1 1 hr before reperfusion. One hour after reperfusion, the right pulmonary artery was clamped for 10 min to assess the function of the transplanted lung. Pulmonary function was assessed again on day 3. RESULTS: Complement inhibition was 93% in the sCR1 group and returned to baseline (8% inhibition) after 3 days. There was a trend toward a higher partial pressure of oxygen at 1 hr in the sCR1 group compared with the control group (mean +/- SE: 408+/-42 mmHg vs. 288+/-69 mmHg, P = 0.19). Alveolar ventilation was better in the sCR1 group than in the control group (P = 0.01) at 1 hr. Mixed venous saturation was significantly lower in the control group at both 1 hr (P = 0.02) and 3 days (P = 0.001). The wet/dry weight of the lung tissue was lower in the sCR1 group compared with the control group on day 3 (P < 0.05). Chemiluminescence, an index of phagocyte priming, was lower in the sCR1 group when cells were stimulated with complement opsonized zymosan but not when stimulated with zymosan or phorbol myristate acetate. CONCLUSION: sCR1 improves ventilation, reduces pulmonary edema, and may be beneficial in improving posttransplant lung oxygenation.
BACKGROUND:Lung dysfunction after transplantation continues to be a significant clinical problem. Soluble complement receptor 1 (sCR1) is a potent inhibitor of complement activation. We evaluated the inhibitory effect of sCR1 on complement activation and reperfusion injury in pig lung allografts. METHODS: In a randomized and blinded study, left lung transplantation was performed in 13 pigs. Donor lungs were flushed and then stored for 30 hr at 4 degrees C. Control pigs (n=7) received saline, and the treatment group (n=6) received 15 mg/kg sCR1 1 hr before reperfusion. One hour after reperfusion, the right pulmonary artery was clamped for 10 min to assess the function of the transplanted lung. Pulmonary function was assessed again on day 3. RESULTS: Complement inhibition was 93% in the sCR1 group and returned to baseline (8% inhibition) after 3 days. There was a trend toward a higher partial pressure of oxygen at 1 hr in the sCR1 group compared with the control group (mean +/- SE: 408+/-42 mmHg vs. 288+/-69 mmHg, P = 0.19). Alveolar ventilation was better in the sCR1 group than in the control group (P = 0.01) at 1 hr. Mixed venous saturation was significantly lower in the control group at both 1 hr (P = 0.02) and 3 days (P = 0.001). The wet/dry weight of the lung tissue was lower in the sCR1 group compared with the control group on day 3 (P < 0.05). Chemiluminescence, an index of phagocyte priming, was lower in the sCR1 group when cells were stimulated with complement opsonized zymosan but not when stimulated with zymosan or phorbol myristate acetate. CONCLUSION: sCR1 improves ventilation, reduces pulmonary edema, and may be beneficial in improving posttransplant lung oxygenation.
Authors: Valeria Ramaglia; Ruud Wolterman; Maryla de Kok; Miriam Ann Vigar; Ineke Wagenaar-Bos; Rosalind Helen Mary King; Brian Paul Morgan; Frank Baas Journal: Am J Pathol Date: 2008-03-18 Impact factor: 4.307
Authors: Qi Cheng; Kunal Patel; Biao Lei; Lindsay Rucker; D Patterson Allen; Peng Zhu; Chentha Vasu; Paulo N Martins; Martin Goddard; Satish N Nadig; Carl Atkinson Journal: Am J Transplant Date: 2018-04-10 Impact factor: 8.086
Authors: Jonathan C Yeung; Dirk Wagnetz; Marcelo Cypel; Matthew Rubacha; Terumoto Koike; Yi-Min Chun; Jim Hu; Thomas K Waddell; David M Hwang; Mingyao Liu; Shaf Keshavjee Journal: Mol Ther Date: 2012-03-27 Impact factor: 11.454
Authors: Hrishikesh S Kulkarni; Kristy Ramphal; Lina Ma; Melanie Brown; Michelle Oyster; Kaitlyn N Speckhart; Tsuyoshi Takahashi; Derek E Byers; Mary K Porteous; Laurel Kalman; Ramsey R Hachem; Melanie Rushefski; Ja'Nia McPhatter; Marlene Cano; Daniel Kreisel; Masina Scavuzzo; Brigitte Mittler; Edward Cantu; Katrine Pilely; Peter Garred; Jason D Christie; John P Atkinson; Andrew E Gelman; Joshua M Diamond Journal: JCI Insight Date: 2020-09-03