Inhaled Nitric Oxide Therapy: Non-response and Rebound Response
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Therapeutic inhaled nitric oxide (INO) has proved beneficial in patients with pulmonary hypertension. However, around 30-40% of the patients are non-responders to this therapy, and a life-threatening rebound response may occur during attempts to withdraw INO. This thesis investigated the link between vasoconstrictors and non- and rebound responses in piglets subjected to acute lung injury by exposure to endotoxin or oleic acid (OA). We found that INO had strong effect in mainly ET-1 related, endotoxin-induced pulmonary hypertension, and there was a rebound response after INO withdrawal. Thus, the weaker the response to INO, the greater the rebound. Neither response nor rebound was seen in oleic acid-induced, mainly prostaglandin related pulmonary hypertension. INO decreased expression of the ET-A receptor, and this might be another signal transduction pathway whereby INO relieves pulmonary vasoconstriction besides increasing c-GMP. Thus INO might have better effect in pulmonary vasoconstriction that is mainly mediated by ET-1 than when other vasoconstrictors are involved in the vascular reaction. Increased production and/or release of vasoconstrictor peptide endothelin-1 (ET-1) during INO, and release of prostaglandin TXA2 and PGF2α after INO withdrawal, were more important causes of the rebound, than a decreasing endogenous NO production during INO. The latter mechanism has been proposed in previous studies. An increase in prostaglandins after INO withdrawal is possibly secondary to the increase in ET-1 during INO. Combination of INO with the COX inhibitor diclofenac blocked the rebound reaction. These findings may open the way for new therapeutic modalities.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2002. , 58 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1201
Anaesthesiology and intensive care, nitric oxide inhalation, rebound response, non-response, endothelin-1, COX inhibitor, prostaglandin, ARDS, endotoxin, oleic acid
Anestesiologi och intensivvård
Anesthesiology and Intensive Care
Research subject Clinical Physiology
IdentifiersURN: urn:nbn:se:uu:diva-3081ISBN: 91-554-5475-5OAI: oai:DiVA.org:uu-3081DiVA: diva2:162217
2002-12-18, Robergsalen, Akademiska Sjukhuset, Ing 40, 4tr, Uppsala, 13:15