Apyrase treatment prevents ischemia–reperfusion injury in rat lung isografts
| Autor: | Mikio Okazaki, Ridong Chen, Nitin A. Das, Daniel Kreisel, Soon Seog Jeong, J. Lai, G.A. Patterson, Alexander S. Krupnick, Xue Lin, Andrew E. Gelman, Wenjun Li, Seiichiro Sugimoto |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Neutrophils medicine.medical_treatment Cold storage Apoptosis Pulmonary Edema Pharmacology Leukocyte Count chemistry.chemical_compound Adenosine Triphosphate Animals Medicine Lung transplantation Bronchopulmonary Sequestration Peroxidase business.industry Apyrase medicine.disease Rats Inbred F344 Recombinant Proteins Rats Adenosine Diphosphate Transplantation Adenosine diphosphate chemistry Reperfusion Injury Immunology Ectonucleoside Triphosphate Diphosphohydrolase 1 Cytokines Surgery Endothelium Vascular Chemokines business Cardiology and Cardiovascular Medicine Adenosine triphosphate Reperfusion injury Lung Transplantation |
| Zdroj: | The Journal of Thoracic and Cardiovascular Surgery. 138(3):752-759 |
| ISSN: | 0022-5223 |
| DOI: | 10.1016/j.jtcvs.2009.04.049 |
| Popis: | Objective Endothelial cells express the ectoenzyme ectonucleoside adenosine triphosphate diphosphohydrolase, an apyrase that inhibits vascular inflammation by catalyzing the hydrolysis of adenosine triphosphate and adenosine diphosphate. However, ectonucleoside adenosine triphosphate diphosphohydrolase expression is rapidly lost following oxidative stress, leading to the potential for adenosine triphosphate and related purigenic nucleotides to exacerbate acute solid organ inflammation and injury. We asked if administration of a soluble recombinant apyrase APT102 attenuates lung graft injury in a cold ischemia reperfusion model of rat syngeneic orthotopic lung transplantation. Methods Male Fisher 344 donor lungs were cold preserved in a low-potassium dextrose solution in the presence or absence of APT102 for 18 hours prior to transplantation into syngeneic male Fisher 344 recipients. Seven minutes after reperfusion, lung transplant recipients received either a bolus of APT102 or vehicle (saline solution). Four hours after reperfusion, APT102- and saline solution–treated groups were evaluated for lung graft function and inflammation. Results APT102 significantly reduced lung graft extracellular pools of adenosine triphosphate and adenosine diphosphate, improved oxygenation, and protected against pulmonary edema. Apyrase treatment was associated with attenuated neutrophil graft sequestration and less evidence of tissue inflammation as assessed by myeloperoxidase activity, expression of proinflammatory mediators, and numbers of apoptotic endothelial cells. Conclusions Administration of a soluble recombinant apyrase promotes lung function and limits the tissue damage induced by prolonged cold storage, indicating that extracellular purigenic nucleotides play a key role in promoting ischemia–reperfusion injury following lung transplantation. |
| Databáze: | OpenAIRE |
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