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Byline: Motohiro Yamashita, Ralph A. Schmid, Shozo Fujino, Joel D. Cooper, G.Alexander Patterson Abstract: Background: Lung allograft ischemia-reperfusion injury, characterized by increased pulmonary vascular resistance, pulmonary edema, and hypoxia, is the most frequent cause of early graft failure. Exogenous nitric oxide has been shown to reduce lung allograft reperfusion injury. During hypoxia, the adenosine triphosphate-sensitive potassium channel is an important ionic channel that links the bioenergetic metabolism to membrane excitability. It has been shown to play a critical role in vascular permeability and in activation of neutrophils and their subsequent interaction with vessel wall cellular components. The purpose of this study was to investigate whether nicorandil, a novel nitric oxide generator and adenosine triphosphate-sensitive potassium-channel opener, might enhance lung preservation and prevent allograft reperfusion injury. Materials and methods: Fourteen dogs underwent left lung allotransplantation. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1[degrees] C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (inspired oxygen fraction 1.0) were assessed for 6 hours before the dogs were put to death. After the assessment, activity of allograft myeloperoxidase and protein levels of bronchoalveolar lavage fluid were measured. Control animals (group I, n = 5) received no nicorandil. In group II (n = 5), the donor lung received nicorandil (24 mg/L) in the flush solution. In addition, recipient animals received nicorandil (0.5 mg/kg, intravenously) just before reperfusion, as well as a continuous infusion (0.74 [+ or -] 0.03 mg/kg per hour) during the 6-hour assessment period. In group III (n = 4), glibenclamide, a selective adenosine triphosphate-sensitive potassium-channel blocker, was administered 15 minutes before nicorandil administration to both donor and recipient. The animals in group III received nicorandil in the same regimen as group II. Result: Superior gas exchange and hemodynamics were observed in lungs receiving only nicorandil. Allograft myeloperoxidase activity and protein levels in bronchoalveolar lavage fluid were significantly reduced in group II. Glibenclamide eliminated the beneficial effects of nicorandil. Conclusions: Nicorandil administration in the flush solution and during the reperfusion period ameliorates lung allograft dysfunction, improves blood flow, and reduces pulmonary vascular resistance and myeloperoxidase activity in the transplanted lung. The present study suggests that nicorandil reduces lung allograft reperfusion injury. The beneficial effects of nicorandil may be attributed to its properties as an adenosine triphosphate-sensitive potassium-channel opener. (J THORAC CARDIOVASC SURG 1996;112:1307-14) Article History: Received 6 May 1996; Revised 20 May 1996; Revised 12 June 1996; Accepted 13 June 1996 Article Note: (footnote) [star] From the Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, Barnes Hospital, St. Louis, Mo., [star][star] Supported by National Institutes of Health grant 12 R01 HL41281 and a grant from Chugai Pharmaceutical Co., Ltd., a Read at the Seventy-sixth Annual meeting of The American Association for Thoracic Surgery, San Diego, Calif., April 28-May 1, 1996., aa Address for reprints: G. Alexander Patterson, MD, Division of Cardiothoracic Surgery, Wahington University School of Medicine, 3108 Queeny Tower, One Barnes Hospital Plaza, St. Louis, MO 63110, acents J Thorac Cardiovasc Surg 1996;112:1307-14, acentsacents 0022-5223/96 $5.00 + 0, a[bar] 12/6/75894

Study objectives: There have been many studies on the physical characteristics at the time of contraction of a primary spontaneous pneumothorax (PSP), but it has not been shown when and [...]