Bronchial circulation plays a critical role in the pathophysiology of
burn and
smoke inhalation-induced
acute lung injury. A 10-fold increase in bronchial blood flow is associated with excessive production of
nitric oxide (NO) following
smoke inhalation and cutaneous
burn. Because an increased release of
neuropeptides from the airway has been implicated in
smoke inhalation injury, we hypothesized that direct delivery into the bronchial artery of low-dose
7-nitroindazole (7-NI), a specific neuronal
NO synthase inhibitor, would attenuate
smoke/
burn-induced
acute lung injury. Eighteen adult female sheep were instrumented for chronic hemodynamic monitoring 5 to 7 days before the injury. The bronchial artery was cannulated via intercostal
thoracotomy, while blood flow was preserved.
Acute lung injury was induced by 40% total body surface area third-degree cutaneous
burn and
smoke inhalation (48 breaths of cotton
smoke, <40°C) under deep
anesthesia. Following injury, animals (35.4 ± 1.1 kg) were divided into three groups: (a) 7-NI group: 1 h after injury, 7-NI (0.01 mg · kg · h, 2 mL · h) was continuously infused into the bronchial artery, n = 6; (b) control group: 1 h after injury, same amount of saline was injected into the bronchial artery, n = 6; (c)
sham group: no injury, no treatment, same operation and
anesthesia, n = 6. After injury, all animals were ventilated and fluid resuscitated according to an established protocol. The experiment was conducted for 24 h. Injury induced severe pulmonary dysfunction, which was associated with increases in lung
edema formation,
airway obstruction,
malondialdehyde, and
nitrate/
nitrite.
7-Nitroindazole injection into the bronchial artery reduced the degree of lung
edema formation and improved pulmonary gas exchange. The increase in
malondialdehyde and
nitrate/
nitrite in lung tissue was attenuated by treatment. Our data strongly suggest that local airway production of NO contributes to pulmonary dysfunction following
smoke inhalation and
burn injury. Most mechanisms that drive this pathophysiology reside in the airway.