Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function

Andrew F. Pierre, Alexandre M. Xavier, Mingyao Liu, Stephen D. Cassivi, Thomas F. Lindsay, Henry C. Marsh, Arthur S. Slutsky, Shaf H. Keshavjee

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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°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.

Original languageEnglish (US)
Pages (from-to)723-732
Number of pages10
JournalTransplantation
Volume66
Issue number6
DOIs
StatePublished - Sep 27 1998
Externally publishedYes

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Complement C1
Complement Receptors
Swine
Lung
Control Groups
Zymosan
Complement Activation
Reperfusion
Ventilation
Lung Transplantation
Partial Pressure
Tetradecanoylphorbol Acetate
Pulmonary Edema
Phagocytes
Luminescence
Reperfusion Injury
Pulmonary Artery
Allografts
Transplantation
Oxygen

ASJC Scopus subject areas

  • Transplantation

Cite this

Pierre, A. F., Xavier, A. M., Liu, M., Cassivi, S. D., Lindsay, T. F., Marsh, H. C., ... Keshavjee, S. H. (1998). Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function. Transplantation, 66(6), 723-732. https://doi.org/10.1097/00007890-199809270-00006

Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function. / Pierre, Andrew F.; Xavier, Alexandre M.; Liu, Mingyao; Cassivi, Stephen D.; Lindsay, Thomas F.; Marsh, Henry C.; Slutsky, Arthur S.; Keshavjee, Shaf H.

In: Transplantation, Vol. 66, No. 6, 27.09.1998, p. 723-732.

Research output: Contribution to journalArticle

Pierre, AF, Xavier, AM, Liu, M, Cassivi, SD, Lindsay, TF, Marsh, HC, Slutsky, AS & Keshavjee, SH 1998, 'Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function', Transplantation, vol. 66, no. 6, pp. 723-732. https://doi.org/10.1097/00007890-199809270-00006
Pierre, Andrew F. ; Xavier, Alexandre M. ; Liu, Mingyao ; Cassivi, Stephen D. ; Lindsay, Thomas F. ; Marsh, Henry C. ; Slutsky, Arthur S. ; Keshavjee, Shaf H. / Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function. In: Transplantation. 1998 ; Vol. 66, No. 6. pp. 723-732.
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abstract = "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°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.",
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AU - Pierre, Andrew F.

AU - Xavier, Alexandre M.

AU - Liu, Mingyao

AU - Cassivi, Stephen D.

AU - Lindsay, Thomas F.

AU - Marsh, Henry C.

AU - Slutsky, Arthur S.

AU - Keshavjee, Shaf H.

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N2 - 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°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.

AB - 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°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.

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