Pharmacologic modulation of alveolar liquid clearance in transplanted lungs by phentolamine and FK506.
BACKGROUND
The lung's capacity to clear alveolar fluid can determine the severity of the edema seen after transplantation. We recently observed that alveolar liquid clearance was decreased in transplanted lungs. This study evaluates the ability of phentolamine and FK506 to modulate the severity of lung injury and the decline in alveolar liquid clearance after transplantation.


METHODS
A canine orthotopic single-lung transplantation model was used. The lungs were preserved with a low-potassium-dextran solution (50 mL/kg) and transplanted after 3 hours of cold ischemia. The experimental protocol included a control group, a phentolamine group, in which donor lungs were infused with phentolamine (2 mg/kg), and a FK506 group, in which the animals received FK506 (25 mg/kg per hour) intravenously during reperfusion. After 4 hours of reperfusion, alveolar liquid clearance, wet-to-dry ratios, lung epithelial Na(+) channel expression, and the response to beta-adrenergic stimulation were measured.


RESULTS
The increase in wet-to-dry ratios of transplanted lungs was less pronounced in the phentolamine and FK506 groups. The FK506 treatment led to improvement of alveolar liquid clearance. Neither phentolamine nor FK506 influenced lung epithelial Na(+) channel expression in transplanted lungs or preserved alveolar cell ability to respond to beta-adrenergic stimulation.


CONCLUSIONS
Phentolamine or FK506 treatment during reperfusion improves alveolar liquid clearance and decreases the severity of lung injury.
Sugita
Makoto
M
Centre de Recherche, CHUM, Montreal, Quebec, Canada.
Berthiaume
Yves
Y
VanSpall
Michael
M
Dagenais
André
A
Ferraro
Pasquale
P
D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D015633:Extravascular Lung Water / Q000187:drug effects* / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D016040:Lung Transplantation / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D010646:Phentolamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D011292:Premedication; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000503:physiopathology*; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000503:physiopathology*; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D007166:Immunosuppressive Agents; D009195:Peroxidase; D016559:Tacrolimus; D010646:Phentolamine