Protective effects of inhaled nitric oxide and gabexate mesilate in lung reperfusion injury after transplantation from non-heart-beat donors

Luh, Shi-Ping; Tsai, Chen-Cheng; Shau, Wen-Yi; Shiau, Shoei-Yn Lin; Jan, I-Shiow; Kuo, Sow-Hsong; Yang, Pan-Chyr

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 21, Issue 2 , Pages 251-259, February 2002

Protective effects of inhaled nitric oxide and gabexate mesilate in lung reperfusion injury after transplantation from non-heart-beat donors

This manuscript was presented at the Transplant 2000 meeting at the Chicago Sheraton Hotel, May 13–17, 2000.

Shi-Ping Luh, MD, PhD
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
Chen-Cheng Tsai, MD
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
Wen-Yi Shau, MD
- Institute of Clinical Research, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
Shoei-Yn Lin Shiau, PhD
- Pharmacology and Toxicology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
I-Shiow Jan, MD
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
Sow-Hsong Kuo, MD
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
Pan-Chyr Yang, MD, PhD
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
- Reprint requests: Pan-Chyr Yang, Department of Medicine, National Taiwan University Hospital. Room 14 to 05, 7 Chun-Shan S Rd, Taipei, Taiwan, Republic of China. Telephone: +011-8862-23123456, ext 2116

Received 19 January 2001; accepted 27 June 2001.

Abstract

Background: The use of lung grafts from non-heart-beat donors (NHBDs) is one way of solving the critical donor organ shortage. Inhaled nitric oxide (NO) and gabexate mesilate (FOY), a protease inhibitor, can attenuate some types of neutrophil-mediated tissue injury. Using an isolated lung ventilation and perfusion model, we studied the effects of these agents on reperfusion injury following lung transplantation from NHBDs.

Methods: Five groups of minipigs were studied. In group 1(n = 6), the lungs were flushed and harvested after cardiac arrest, and were reperfused for 2 hours after 2 hours of cold ischemia. In group 2 (n = 6), the lungs were harvested after 2 hours of in situ warm ischemia, followed by 2 hours of cold ischemia and 2 hours of reperfusion. In groups 3 (n = 7), 4 (n = 7), and 5 (n = 6), the procedure was the same as in group 2, except in group 3, NO was inhaled before and after ischemia, in group 4, FOY was given intravenously, and in group 5, a combination of inhaled NO and intravenous FOY were administered.

Results: Compared with group 1, group 2 had higher mean pulmonary arterial pressure, vascular resistance, and lower arterial blood oxygen tension. Furthermore, these negative effects of warm ischemia were also reflected in the contents of bronchoalveolar lavage fluid, tissue myeloperoxidase (MPO) activity, histology, and permeability change. Either FOY or NO administration (groups 3 or 4) ameliorated the associated injury. A combination of FOY and NO use (group5) decreased the parameters of lung reperfusion injury measurement to a larger degree than either agent individually.

Conclusions: The inhaled NO and FOY can protect NHBD lung grafts at an early reperfusion period. Their use in combination has an additive protective effect that might be applied to the protection of NHBD grafts from preservation and reperfusion injury.