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Preservation with 8-bromo-cyclic GMP improves pulmonary function after prolonged ischemia
R C King1, V E Laubach, R C Kanithanon
1Department of Surgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
The Annals of Thoracic Surgery
|January 6, 1999
Summary
Adding 8-bromo-cGMP to preservation solution improved lung function after prolonged hypothermic ischemia. This cyclic guanosine monophosphate (cGMP) analogue enhanced pulmonary vasodilatation and reduced injury better than standard methods.
Area of Science:
- Cardiovascular Science
- Organ Transplantation
- Biochemistry
Background:
- Cyclic guanosine monophosphate (cGMP) is a key second messenger in the nitric oxide pathway, crucial for pulmonary vascular tone.
- Elevated cGMP levels promote pulmonary vasodilation, reducing vascular resistance and improving lung function, especially after ischemia-reperfusion injury.
- Current preservation solutions may not fully mitigate reperfusion injury during prolonged hypothermic storage.
Purpose of the Study:
- To investigate the efficacy of adding a membrane-permeable cGMP analogue (8-bromo-cGMP) to a Euro-Collins (EC) preservation solution.
- To compare the protective effects of 8-bromo-cGMP-enriched EC solution against prostaglandin E1 (PGE1) injection alone in ameliorating pulmonary reperfusion injury.
- To evaluate the impact of prolonged hypothermic ischemia on lung function and biochemical markers when preserved with EC solution with or without 8-bromo-cGMP.
Main Methods:
- New Zealand White rabbit lungs were harvested and flushed with EC solution.
- Lungs underwent prolonged hypothermic storage (18 or 30 hours) with either standard EC solution or EC solution supplemented with 200 µmol/L 8-bromo-cGMP.
- Post-storage, lungs were reperfused with whole blood, and pulmonary function (oxygenation, pressure, resistance) and tissue markers (cGMP, cAMP, NOS activity, myeloperoxidase, wet/dry weight) were assessed.
Main Results:
- Addition of 8-bromo-cGMP to the EC solution significantly improved oxygenation, pulmonary artery pressure, pulmonary vascular resistance, and reduced edema formation in lungs stored for 18 and 30 hours.
- Hypothermic storage, regardless of preservation solution, led to decreased nitric oxide synthase (NOS) activity and myeloperoxidase levels compared to immediate reperfusion.
- The 8-bromo-cGMP group demonstrated superior functional recovery compared to controls after extended cold storage.
Conclusions:
- Supplementing EC preservation solution with 8-bromo-cGMP enhances pulmonary function following prolonged hypothermic ischemia and reperfusion.
- This cGMP analogue offers a potential improvement over standard EC preservation and PGE1 treatment for lung preservation.
- Reduced myeloperoxidase levels post-hypothermic storage and reperfusion suggest a significant role for pulmonary hemodynamic control in mitigating lung injury.