Inhibitor of neuronal nitric oxide synthase improves gas exchange in ventilator-induced lung injury after pneumonectomy

BMC Anesthesiology

Lars J Bjertnaes²  Mikhail Y Kirov³  Vsevolod V Kuzkov³  Andrey Y Valkov¹  Timofey V Kondratiev²  Alexey A Smetkin³  Evgeny V Suborov² 

[1]Institute of Medical Biology, University of Tromsø, 9037, Tromsø, Norway

[2]Anesthesia and Critical Care Research Group, Institute of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway

[3]Department of Anesthesiology, Northern State Medical University, Arkhangelsk, Russian Federation

关键词: 7-nitroindazole;    Ventilator-induced lung injury;    Nitric oxide;    Sheep;    Pulmonary edema;    nNOS;    Mechanical ventilation;    Pneumonectomy;   

Others  :  817062
DOI  :  10.1186/1471-2253-12-10

 received in 2012-01-13, accepted in 2012-06-06,  发布年份 2012

【 摘 要 】

Background

Mechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI) and enhanced generation of nitric oxide (NO). We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS), which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy.

Methods

Anesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (V_T) of 6 mL/kg and FiO₂ 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8) keeping V_T and FiO₂ unchanged, respiratory rate (RR) 25 inflations/min and PEEP 4 cm H₂O for the following 8 hrs; an injuriously ventilated group with V_T of 12 mL/kg, zero end-expiratory pressure, and FiO₂ and RR unchanged (INJV; n = 8) and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI) 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8). We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI). We measured plasma nitrite/nitrate (NOx) levels and examined lung biopsies for lung injury score (LIS).

Results

Both the injuriously ventilated groups demonstrated a 2–3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group.

Conclusion

Inhibition of nNOS improved gas exchange, but did not reduce lung water extravasation following injurious ventilation after pneumonectomy in sheep.

【 授权许可】

   
2012 Suborov et al.; licensee BioMed Central Ltd.

【 图 表 】

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