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Eur J Cardiothorac Surg 2007;31:475-481. doi:10.1016/j.ejcts.2006.11.051
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Pulmonary arterial reactivity during induced infection of single lung allografts

Mayo Clinic College of Medicine, Rochester, MN 55905, United States

Received 13 September 2006; received in revised form 22 November 2006; accepted 28 November 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. (Email: miller.virginia{at}mayo.edu).

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 N^G-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.

Key Words: Endothelium-dependent relaxation • Histamine • Nitric oxide • Rejection