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J Thorac Cardiovasc Surg 1996;111:259-267
© 1996 Mosby, Inc.

CARDIAC AND PULMONARY REPLACEMENT

DELTA OPIOID EXTENDS HYPOTHERMIC PRESERVATION TIME OF THE LUNG

Lexington, Ky., and Baltimore, Md.

Supported by National Institutes of Health grant Nos. GM-43890 and HL-36552.

Received for publication July 20, 1994. Accepted for publication April 27, 1995. Address for reprints: Sufan Chien, MD, Department of Surgery, University of Kentucky Medical Center, 800 Rose St., Lexington, KY 40536.

Abstract

To test the hypothesis that a delta opioid, DADLE ([D-Ala², D-Leu⁵]-enkephalin), could protect tissue from ischemic damage during hypothermic lung preservation, we studied three groups of rats. In group 1 (n = 8), lung function was studied immediately after harvesting. In group 2 (n = 8), the lung was flushed with 4º C Euro-Collins solution and preserved for 24 hours. In group 3 (n = 8), the lung was flushed with 4º C Euro-Collins solution plus DADLE (1 mg/kg) and preserved for 24 hours. Lung function was studied by using a living rat perfusion model. Venous blood from the host rat perfused the pulmonary artery of the isolated lung. Blood from the isolated lung was returned to the carotid artery of the host rat with a roller pump. Severe pulmonary edema, hemorrhage, and occlusive pulmonary artery resistance occurred in group 2 within 30 minutes of perfusion. Perfusion studies were carried out for more than 60 minutes in groups 1 and 3. Pulmonary blood flow was lower in group 2 than in either group 1 or group 3. Pulmonary vascular resistance was much higher in group 2 than in groups 1 and 3 (p < 0.05). Airway pressure and airway resistance were much higher in group 2 than in groups 1 and 3 (p < 0.05). Airway resistance was also higher in group 3 than in group 1 after 20 minutes of perfusion (p < 0.05). Oxygen tensions from the pulmonary vein of the isolated lung in group 2 were lower than those in groups 1 and 3 (p < 0.05). Alveolar-arterial oxygen difference was much higher in group 2 than in groups 1 and 3 (p < 0.05). Lung tissue wet/dry weight ratio after perfusion was much higher in group 2 than in groups 1 and 3. The results clearly show, for the first time, that DADLE can effectively enhance hypothermic lung preservation in rats.(J THORAC CARDIOVASC SURG 1996;111:259-67)

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