Objective: Infection is a major cause of mortality in the first year following single lung transplantation and is a distinct risk factor for the development of obliterative bronchiolitis. However, little is known about changes in pulmonary vascular activity in the setting of infection, which might affect and limit function of the graft. Therefore, the aim of this study was to determine how acute infection altered pulmonary arterial reactivity in single lung allografts. Such information could help to develop better diagnostic and therapeutic targets to improve outcome when grafts become infected. Methods: Following single lung transplantation, dogs were immunosuppressed with methylprednisolone acetate, cyclosporine and azathioprine. On postoperative day 5, infection was induced in one group of dogs by endobronchial inoculation of antibiotic resistant Eschericia coli (infection group, n = 5); in the second group, the same amount of culture media without bacteria was flushed into the bronchus (control group, n = 4). All animals were medicated under the same drug protocol. On postoperative day 8, lungs were removed, reviewed for histological assessment, pulmonary arteries were isolated, cut into rings and suspended for pharmacological characterization in organ chambers. Results: With acute infections, contractions to phenylephrine and angiotensin-1, but not endothelin-1, were reduced in pulmonary arteries with but not without endothelium. Inhibition of nitric oxide synthase with NG-monomethyl-l-arginine, monoacetate salt (l-NMMA) restored these contractions. Endothelium-dependent relaxations to adenosine diphosphate and calcium ionophore, which stimulate release of endothelium-derived nitric oxide by a receptor and non-receptor mediated process, respectively, were not different between groups. Relaxations to nitric oxide also were not different between groups. Conclusion: These results suggest that acute infection selectively reduces contractions of pulmonary arteries in part through receptor-mediated release of nitric oxide from the endothelium. Inhibiting nitric oxide during episodes of acute infection may help to improve graft perfusion during episodes of acute infection.
Bibliographical noteFunding Information:
§ Presented at the joint 20th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society of Thoracic Surgeons, Stockholm, Sweden, September 10—13, 2006. * Corresponding author. Address: Mayo Clinic College of Medicine, 4-62 Medical Sciences Bldg., 200 First Street SW, Rochester, MN 55905, United States. Tel.: +1 507 284 2290; fax: +1 507 266 2233. E-mail address: firstname.lastname@example.org (V.M. Miller). 1 Hae Kyoon Kim was a visiting scientist supported by grants from the Yonsei University College of Medicine, Seoul Yongdong, 1217 Seoul, Korea. 2 Young-Sik Park was a was a visiting scientist supported by grants from the Ewha Women’s University, Makdong Hospital, 158-056 Yangcheonku, Seoul, Korea.
Supported by the Mayo Clinic and Foundation. Mr Ronald Lee, Mr Kevin Rud and Ms Sandy Severson are thanked for their expert technical assistance; Ms Beth Allred is thanked for her secretarial help with manuscript preparation.
- Endothelium-dependent relaxation
- Nitric oxide