Selective adenosine-A(2A) activation reduces lung reperfusion injury following transplantation

Scott D. Ross, Curtis G. Tribble, Joel Linden, James J. Gangemi, Brendan C. Lanpher, Andrew Y. Wang, Irving L. Kron

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Background: The adenosine-A(2A) receptor on the neutrophil is responsible for several anti-inflammatory actions. We hypothesized that DWH- 146e, a selective adenosine-A(2A) agonist, would reduce lung reperfusion injury following transplantation. Methods: We used an isolated, whole blood- perfused, ventilated rabbit lung model. Donor rabbits underwent lung harvest after pulmonary arterial PGE1 injection and Euro-Collins preservation solution flush, and lungs were preserved for 18 hours at 4°C. Group I lungs (n = 9) served as control subjects. Group II lungs (n = 9) were reperfused with whole blood that was first passed through a leukocyte-depleting filter. In group III (n = 9), DWH-146e was added to the blood reperfusate (25 μg/kg) immediately before reperfusion and was administered throughout the reperfusion period (1 μg/kg/min). All lungs were reperfused for 30 minutes. Results: Arterial oxygenation in group II and group III was significantly higher than that of group I after 30 minutes of reperfusion (514.27 ± 35.80 and 461.12 ± 43.77 vs 91.41 ± 20.58 mm Hg, p < .001). Pulmonary vascular resistance was significantly reduced in group III (22,783 ± 357 dynes · s · cm-5) compared to both group II and group I (31,057 ± 1743 and 36,911 ± 2173 dynes · s · cm-5, p < .001). Airway compliance was improved in groups II and III when compared to group I (1.68 ± 0.08 and 1.68 ± 0.05 vs 1.36 ± 0.13, p = .03). Microvascular permeability in group III was reduced to 106.82 ± 17.09 compared with 165.70 ± 21.83 ng Evans blue dye per gram of tissue in group I (p = .05). Group III myeloperoxidase activity was 39.88 ± 4.87 compared with 88.70 ± 18.69 ΔOD/g/min in group I (p = .03); group II myeloperoxidase activity was 56.06 ± 7.46. Conclusions: DWH-146e reduced lung neutrophil sequestration and dramatically improved pulmonary graft function. Neutrophils are important components of the inflammatory cascade of reperfusion injury and their source may include both the circulating blood and the lung graft itself. Selective adenosine-A(2A) activation interrupts the neutrophil-mediated inflammatory response and reduces lung reperfusion injury following transplantation.

Original languageEnglish (US)
Pages (from-to)994-1002
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume18
Issue number10
DOIs
StatePublished - Oct 1 1999
Externally publishedYes

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Lung Injury
Reperfusion Injury
Adenosine
Transplantation
Lung
Reperfusion
Neutrophils
Peroxidase
Adenosine A2A Receptors
Rabbits
Transplants
Evans Blue
Neutrophil Activation
Alprostadil
Capillary Permeability
Vascular Resistance
Compliance
Leukocytes
Anti-Inflammatory Agents
Coloring Agents

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

Selective adenosine-A(2A) activation reduces lung reperfusion injury following transplantation. / Ross, Scott D.; Tribble, Curtis G.; Linden, Joel; Gangemi, James J.; Lanpher, Brendan C.; Wang, Andrew Y.; Kron, Irving L.

In: Journal of Heart and Lung Transplantation, Vol. 18, No. 10, 01.10.1999, p. 994-1002.

Research output: Contribution to journalArticle

Ross, Scott D. ; Tribble, Curtis G. ; Linden, Joel ; Gangemi, James J. ; Lanpher, Brendan C. ; Wang, Andrew Y. ; Kron, Irving L. / Selective adenosine-A(2A) activation reduces lung reperfusion injury following transplantation. In: Journal of Heart and Lung Transplantation. 1999 ; Vol. 18, No. 10. pp. 994-1002.
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abstract = "Background: The adenosine-A(2A) receptor on the neutrophil is responsible for several anti-inflammatory actions. We hypothesized that DWH- 146e, a selective adenosine-A(2A) agonist, would reduce lung reperfusion injury following transplantation. Methods: We used an isolated, whole blood- perfused, ventilated rabbit lung model. Donor rabbits underwent lung harvest after pulmonary arterial PGE1 injection and Euro-Collins preservation solution flush, and lungs were preserved for 18 hours at 4°C. Group I lungs (n = 9) served as control subjects. Group II lungs (n = 9) were reperfused with whole blood that was first passed through a leukocyte-depleting filter. In group III (n = 9), DWH-146e was added to the blood reperfusate (25 μg/kg) immediately before reperfusion and was administered throughout the reperfusion period (1 μg/kg/min). All lungs were reperfused for 30 minutes. Results: Arterial oxygenation in group II and group III was significantly higher than that of group I after 30 minutes of reperfusion (514.27 ± 35.80 and 461.12 ± 43.77 vs 91.41 ± 20.58 mm Hg, p < .001). Pulmonary vascular resistance was significantly reduced in group III (22,783 ± 357 dynes · s · cm-5) compared to both group II and group I (31,057 ± 1743 and 36,911 ± 2173 dynes · s · cm-5, p < .001). Airway compliance was improved in groups II and III when compared to group I (1.68 ± 0.08 and 1.68 ± 0.05 vs 1.36 ± 0.13, p = .03). Microvascular permeability in group III was reduced to 106.82 ± 17.09 compared with 165.70 ± 21.83 ng Evans blue dye per gram of tissue in group I (p = .05). Group III myeloperoxidase activity was 39.88 ± 4.87 compared with 88.70 ± 18.69 ΔOD/g/min in group I (p = .03); group II myeloperoxidase activity was 56.06 ± 7.46. Conclusions: DWH-146e reduced lung neutrophil sequestration and dramatically improved pulmonary graft function. Neutrophils are important components of the inflammatory cascade of reperfusion injury and their source may include both the circulating blood and the lung graft itself. Selective adenosine-A(2A) activation interrupts the neutrophil-mediated inflammatory response and reduces lung reperfusion injury following transplantation.",
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T1 - Selective adenosine-A(2A) activation reduces lung reperfusion injury following transplantation

AU - Ross, Scott D.

AU - Tribble, Curtis G.

AU - Linden, Joel

AU - Gangemi, James J.

AU - Lanpher, Brendan C.

AU - Wang, Andrew Y.

AU - Kron, Irving L.

PY - 1999/10/1

Y1 - 1999/10/1

N2 - Background: The adenosine-A(2A) receptor on the neutrophil is responsible for several anti-inflammatory actions. We hypothesized that DWH- 146e, a selective adenosine-A(2A) agonist, would reduce lung reperfusion injury following transplantation. Methods: We used an isolated, whole blood- perfused, ventilated rabbit lung model. Donor rabbits underwent lung harvest after pulmonary arterial PGE1 injection and Euro-Collins preservation solution flush, and lungs were preserved for 18 hours at 4°C. Group I lungs (n = 9) served as control subjects. Group II lungs (n = 9) were reperfused with whole blood that was first passed through a leukocyte-depleting filter. In group III (n = 9), DWH-146e was added to the blood reperfusate (25 μg/kg) immediately before reperfusion and was administered throughout the reperfusion period (1 μg/kg/min). All lungs were reperfused for 30 minutes. Results: Arterial oxygenation in group II and group III was significantly higher than that of group I after 30 minutes of reperfusion (514.27 ± 35.80 and 461.12 ± 43.77 vs 91.41 ± 20.58 mm Hg, p < .001). Pulmonary vascular resistance was significantly reduced in group III (22,783 ± 357 dynes · s · cm-5) compared to both group II and group I (31,057 ± 1743 and 36,911 ± 2173 dynes · s · cm-5, p < .001). Airway compliance was improved in groups II and III when compared to group I (1.68 ± 0.08 and 1.68 ± 0.05 vs 1.36 ± 0.13, p = .03). Microvascular permeability in group III was reduced to 106.82 ± 17.09 compared with 165.70 ± 21.83 ng Evans blue dye per gram of tissue in group I (p = .05). Group III myeloperoxidase activity was 39.88 ± 4.87 compared with 88.70 ± 18.69 ΔOD/g/min in group I (p = .03); group II myeloperoxidase activity was 56.06 ± 7.46. Conclusions: DWH-146e reduced lung neutrophil sequestration and dramatically improved pulmonary graft function. Neutrophils are important components of the inflammatory cascade of reperfusion injury and their source may include both the circulating blood and the lung graft itself. Selective adenosine-A(2A) activation interrupts the neutrophil-mediated inflammatory response and reduces lung reperfusion injury following transplantation.

AB - Background: The adenosine-A(2A) receptor on the neutrophil is responsible for several anti-inflammatory actions. We hypothesized that DWH- 146e, a selective adenosine-A(2A) agonist, would reduce lung reperfusion injury following transplantation. Methods: We used an isolated, whole blood- perfused, ventilated rabbit lung model. Donor rabbits underwent lung harvest after pulmonary arterial PGE1 injection and Euro-Collins preservation solution flush, and lungs were preserved for 18 hours at 4°C. Group I lungs (n = 9) served as control subjects. Group II lungs (n = 9) were reperfused with whole blood that was first passed through a leukocyte-depleting filter. In group III (n = 9), DWH-146e was added to the blood reperfusate (25 μg/kg) immediately before reperfusion and was administered throughout the reperfusion period (1 μg/kg/min). All lungs were reperfused for 30 minutes. Results: Arterial oxygenation in group II and group III was significantly higher than that of group I after 30 minutes of reperfusion (514.27 ± 35.80 and 461.12 ± 43.77 vs 91.41 ± 20.58 mm Hg, p < .001). Pulmonary vascular resistance was significantly reduced in group III (22,783 ± 357 dynes · s · cm-5) compared to both group II and group I (31,057 ± 1743 and 36,911 ± 2173 dynes · s · cm-5, p < .001). Airway compliance was improved in groups II and III when compared to group I (1.68 ± 0.08 and 1.68 ± 0.05 vs 1.36 ± 0.13, p = .03). Microvascular permeability in group III was reduced to 106.82 ± 17.09 compared with 165.70 ± 21.83 ng Evans blue dye per gram of tissue in group I (p = .05). Group III myeloperoxidase activity was 39.88 ± 4.87 compared with 88.70 ± 18.69 ΔOD/g/min in group I (p = .03); group II myeloperoxidase activity was 56.06 ± 7.46. Conclusions: DWH-146e reduced lung neutrophil sequestration and dramatically improved pulmonary graft function. Neutrophils are important components of the inflammatory cascade of reperfusion injury and their source may include both the circulating blood and the lung graft itself. Selective adenosine-A(2A) activation interrupts the neutrophil-mediated inflammatory response and reduces lung reperfusion injury following transplantation.

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