Abstract
Long-term survival following lung transplantation has been limited primarily by the development in patients’ lungs of a rejection-related obliteration of terminal bronchioles by fibroblasts. It is known to result from frequent and persistent acute lung rejection and its physiological features include a progressive decline in the lung function measurement of forced expiratory volume in1 s. We report the dramatic effect on this hitherto usually fatal condition of a specific inhibitionof purine metabolism at the xanthine oxidase enzyme by the hypoxanthine analogue allopurinol. The effect of this drug in heart-lung transplant patients with deteriorating lung function in reducing therate of rejection and in stabilizing lung function was apparent over as short a follow-up period as 3 months and in ten patients. Although the follow-up time is short, we believe the effects are so striking as to require reporting although the mechanisms of this phenomenon are not yet well understood.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bonser RS, Fragomeni LS, Edwards BJ, et al (1990) Allopurinol and desferoximine improve canine lung preservation. Transplant Proc 22:557–558
Burke CM, Theodore J, Baldwin JC, et al (1986) Twenty-eight cases of human heart-lung transplantation. Lancet 1:517–519
Clelland CAC, Higenbottam TW, Otulana BA, et al (1990) Histological classification of acute lung rejection in heart-lung transplantation. J Heart Transplant 9:177–186
Elion GB, Callahan S, Rundles RW, Hitchings GH (1963) Relationship between metabolic fates and antitumor activities of thiopurines. Cancer Res 23:1207–1217
Fogt F, Zilker T (1981) Total exclusion from external respiration protects lungs from the development of fibrosis after paraquat in the immunosuppressed host. Clin Chest Med 2:19–39
Glandville AR, Baldwin JC, Burke CM, Theodore J, Robin ED (1987) Obliterative bronchiolitis after heart-lung transplantation: Apparent arrest by augmented immunosuppression. Ann Intern Med 107:300–304
Griffith BP, Paradis IL, Zeevi A, et al (1988) Immunologically mediated disease of the airways after pulmonary transplantation. Ann Surg 208:371–378
Gruber DF, O’Halloran KP, Farese AM (1989) Xanthine oxidase potentiation of reactive oxygen intermediates in isolated canine peripheral neutrophils. J Biol Response Mod 8:462–467
Hajjar GB, Toledo-Pereyra LH, MacKenzie GH (1987) Twenty-four hour heart-lung preservation and oxygen free radical scavengers. Transplant Proc 19:1342–1344
Junod AF (1989) Oxygen free radicals and the lungs. Intensive Care Med 15:S21–23
Kennedy TP, Rao NV, Hopkins C, Pennington L, Tolley E, Hoidal JR (1990) Role of reactive oxygen molecules in experimental colitis. Gut 31:786–790
Kriett JM, Kaye MP (1990) The registry of the international society for heart transplantation: seventh official report-1990. J Heart Transplant 9:323–330
Miyazawa T, Fujimoto K, Oikawa S (1990) Determination of lipid hydroperoxides in low density lipoprotein from human plasma using high performance liquid chromatography with chemiluminescence detection. Biomed Chromatogr 4:131–134
Murrell GA, Francis MJ, Bromley L (1990) Modulation of fibroblast proliferation by oxygen free radicals. Biochem J 265:659–665
Scott JP, Higenbottam TW, Clelland CAC, et al (1989) The natural history of obliterative bronchiolitis and occlusive vascular disease of patients following heart-lung transplantation. Transplant Proc 21:2592–2593
Scott JP, Higenbottam TW, Sharpies L, et al (1991) Risk factors for obliterative bronchiolitis in heart-lung transplant recipients. Transplantation (in press)
Yousem SA, Burke CM, Billingham ME (1985) Pathologic pulmonary alterations in long-term human heart-lung transplantation. Hum Pathol 16:911–923
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Wallwork, J., Scott, J.P. (1992). The use of allopurinol in the inhibition of obliterative bronchiolitis of the transplanted lung. In: Kootstra, G., Opelz, G., Buurman, W.A., van Hooff, J.P., MacMaster, P., Wallwork, J. (eds) Transplant International Official Journal of the European Society for Organ Transplantation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77423-2_78
Download citation
DOI: https://doi.org/10.1007/978-3-642-77423-2_78
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-55342-7
Online ISBN: 978-3-642-77423-2
eBook Packages: Springer Book Archive