HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/L1300    most recent 00396.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Liu, R. Articles by Zapol, W. M. Search for Related Content PubMed PubMed Citation Articles by Liu, R. Articles by Zapol, W. M.

Congenital NOS2 deficiency prevents impairment of hypoxic pulmonary vasoconstriction in murine ventilator-induced lung injury

¹Department of Anesthesia and Critical Care and ²Cardiovascular Research Center of Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Submitted 5 October 2006 ; accepted in final form 23 August 2007

Hypoxic pulmonary vasoconstriction (HPV) preserves systemic arterial oxygenation during lung injury by diverting blood flow away from poorly ventilated lung regions. Ventilator-induced lung injury (VILI) is characterized by pulmonary inflammation, lung edema, and impaired HPV leading to systemic hypoxemia. Studying mice congenitally deficient in inducible nitric oxide synthase (NOS2) and wild-type mice treated with a selective NOS2 inhibitor, L-N⁶-(1-iminoethyl)lysine (L-NIL), we investigated the contribution of NOS2 to the impairment of HPV in anesthetized mice subjected to 6 h of either high tidal volume (HV_T) or low tidal volume (LV_T) ventilation. HPV was estimated by measuring the changes of left lung pulmonary vascular resistance (LPVR) in response to left mainstem bronchus occlusion (LMBO). LMBO increased the LPVR similarly in wild-type, NOS2^–/–, and wild-type mice treated with L-NIL 30 min before commencing 6 h of LV_T ventilation (96% ± 30%, 103% ± 33%, and 80% ± 16%, respectively, means ± SD). HPV was impaired in wild-type mice subjected to 6 h of HV_T ventilation (23% ± 16%). In contrast, HPV was preserved after 6 h of HV_T ventilation in NOS2^–/– and wild-type mice treated with L-NIL either 30 min before or 6 h after commencing HV_T ventilation (66% ± 22%, 82% ± 29%, and 85% ± 16%, respectively). After 6 h of HV_T ventilation and LMBO, systemic arterial oxygen tension was higher in NOS2^–/– than in wild-type mice (192 ± 11 vs. 171 ± 17 mmHg; P < 0.05). We conclude that either congenital NOS2 deficiency or selective inhibition of NOS2 protects mice from the impairment of HPV occurring after 6 h of HV_T ventilation.

mechanical ventilation; nitric oxide synthase; hypoxia