Inducible nitric oxide synthase dimerization inhibitor prevents cardiovascular and renal morbidity in sheep with combined burn and smoke inhalation injury

Inducible nitric oxide synthase (iNOS) is implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). ARDS treatment is frequently complicated by significant extrapulmonary comorbidity. This study was designed to clarify the role of iNOS in mediating extrapulmonary comorbidity in sheep after combined burn and smoke inhalation injuries using a potent and highly selective iNOS dimerization inhibitor, BBS-2. Twenty-two female sheep were operatively prepared. After 5 days of recovery, tracheostomy was performed under ketamine-halothane anesthesia. Sheep were given a 40% total body surface third-degree burns and insufflated with cotton smoke (48 breaths,