Postpneumonectomy pulmonary edema and the nitric oxide pathway : experimental studies in sheep

Suborov, Evgeny

dc.contributor.advisor	Bjertnaes, Lars
dc.contributor.author	Suborov, Evgeny
dc.date.accessioned	2012-11-26T12:04:55Z
dc.date.available	2012-11-26T12:04:55Z
dc.date.issued	2012-11-07
dc.description.abstract	Ventilator-induced lung injury after pneumonectomy, a life-threatening complication of excessive one-lung mechanical ventilation Lung edema after lung resection is associated with a mortality of 50–100% and no cure. In sheep we found that removal of one lung followed by excessive one-lung ventilation triggered a severe lung injury with lung edema. This is a novel model of acute lung injury (ALI) in a large animal. Inhibition of neuronal nitric oxide synthase improved oxygenation, but did not prevent lung edema from developing.	en
dc.description.doctoraltype	ph.d.	en
dc.description.popularabstract	Lung edema after resection of a lung is a life-threatening subtype of ALI. Excessive mechanical ventilation with low end-expiratory pressure may result in damage to the lungs, referred to as ventilator - induced lung injury (VILI). Studies of VILI in small mammals have demonstrated an involvement of the nitric oxide (NO) pathway. We and other investigators have shown that NO synthase inhibitors modulate various subtypes of ALI. We speculated if removal of one lung followed by excessive one-lung ventilation and zero end-expiratory pressure promotes VILI and whether this subtype of ALI is attenuated by the inhibitor of endothelial and inducible NO synthase (NOS), methylene blue, or the inhibitor of neuronal NOS (nNOS), 7-nitroindazole. After surgical removal of one lung, the anesthetized sheep was randomized to groups of protective or injurious ventilation, consisting of tidal volumes of 6 and 12 ml/kg, respectively. In sheep exposed to injurious ventilation with excessive tidal volumes and zero end-expiratory pressure, lung edema occurred in concert with derangement of gas exchange that were uninfluenced by methylene blue. In contrast, infusion of an inhibitor of nNOS, improved gas exchange, most likely by reinforcement of hypoxic pulmonary vasoconstriction, but did not influence the pulmonary edema development. Thus, our experiments do not indicate a major role of nitric oxide or its metabolites in the pathogenesis of this condition. Nevertheless, other compounds should be investigated for potential effects on this subtype of acute lung injury.	en
dc.description	Papers 1 & 2 of the thesis are not available in Munin: <br/>1. V.V. Kuzkov, E.V. Suborov, M.Y. Kirov, V.N. Kuklin, M. Sobhkhez, S. Johnsen, K. Waerhaug and L.J. Bjertnaes: 'Extravascular lung water after pneumonectomy and one-lung ventilation in sheep', Critical Care Medicine (2007), vol. 35, no. 6:1550-1559. Available at <a href=http://dx.doi.org/10.1097/01.CCM.0000265739.51887.2B>http://dx.doi.org/10.1097/01.CCM.0000265739.51887.2B</a> <br/>2. E.V. Suborov, V.V. Kuzkov, M. Sobhkhez, M.Y. Kirov and L.J. Bjertnaes: 'The effects of methylene blue on ovine post-pneumonectomy pulmonary oedema', Acta Anaesthesiologica Scandinavica (2010), vol. 54, no. 9:1089–109. Available at <a href=http://dx.doi.org/10.1111/j.1399-6576.2010.02287.x>http://dx.doi.org/10.1111/j.1399-6576.2010.02287.x</a>	en
dc.identifier.isbn	978-82-7589-373-2
dc.identifier.uri	https://hdl.handle.net/10037/4634
dc.identifier.urn	URN:NBN:no-uit_munin_4349
dc.language.iso	eng	en
dc.publisher	University of Tromsø	en
dc.publisher	Universitetet i Tromsø	en
dc.rights.accessRights	openAccess
dc.rights.holder	Copyright 2012 The Author(s)
dc.rights.uri	https://creativecommons.org/licenses/by-nc-sa/3.0	en_US
dc.rights	Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)	en_US
dc.subject	VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Lung diseases: 777	en
dc.subject	VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Lungesykdommer: 777	en
dc.subject	VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Human and veterinary science physiology: 718	en
dc.subject	VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Human og veterinærmedisinsk fysiologi: 718	en
dc.title	Postpneumonectomy pulmonary edema and the nitric oxide pathway : experimental studies in sheep	en
dc.type	Doctoral thesis	en
dc.type	Doktorgradsavhandling	en