Lidocaine attenuates hyperoxic lung injury in rabbits.
BACKGROUND
High concentrations of oxygen acute lung injury. Neutrophils are thought to play a pivotal role in the pathogenesis of this lung injury through the release of oxygen radicals, neutral proteases, and lysosomal enzymes. Lidocaine has been shown to inhibit neutrophil function. We examined whether intravenous pretreatment with lidocaine attenuated acute lung injury induced by hyperoxia.


METHODS
Twenty-seven anaesthetized male rabbits were allocated to receive one of three treatments (n = 9 for each group): ventilation with 100% oxygen for 36 h with and without lidocaine treatment, and ventilation with air for 36 h without lidocaine. In the lidocaine-treated group, a single intravenous lidocaine 2 mg/kg was administered immediately after the initiation of exposure to 100% oxygen; thereafter, the lidocaine was infused at a rate of 2 mg.kg(-1).h(-1) for 36 h until the animals were sacrificed. Haemodynamics, PaO2, and lung mechanics were recorded during the ventilation period. After exposure, the lung mechanics and cell fraction in bronchoalveolar lavage fluid (BALF) were measured and analyzed, as was the concentration of activated complements, and cytokines in BALF. The lung wet-to dry- (W/D) weight ratio and albumin concentrations in BALF were analyzed as an index of pulmonary oedema. We also compared the chemiluminescence of neutrophils isolated from the pulmonary artery, and light microscopic findings, in the three groups.


RESULTS
Pure oxygen for 36 h caused no significant changes in haemodynamics, lung mechanics, or PaO2/FiO2 ratio. However, hyperoxia significantly increased the lung W/D weight ratio, the influx of neutrophils into the lung, and BALF concentrations of C3a, C5a, TNF-alpha, IL-1 beta, and albumin. Lidocaine attenuated these increases (W/D ratio: 5.7 vs 5.1, %PMN: 19.2% vs 1.6%, C3a: 62 ng/dl vs 14 ng/dl, C5a: 7.9 ng/dl vs 4.1 nd/dl, TNF-alpha: 25 fmol/ml vs 2.8 fmol/ml, IL-1 beta: 36 fmol/ml vs 2.2 fmol/ml, and albumin: 9.5 mg/dl vs 2.8 mg/dl, all: P < 0.05). The chemiluminescence was increased in hyperoxic compared with in normoxic rabbits and lidocaine treatment attenuated the increase (opsonized zymosan stiluated: 3.7 x 10(6) cpm vs 2.3 x 10(6) cpm, P < 0.05). Exposure to 100% oxygen caused extensive morphologic lung damage which was lessened by lidocaine (lung injury score (mean): 3 vs 4, P < 0.05).


CONCLUSIONS
These findings suggest that intravenous lidocaine has a prophylactic effect on initial hyperoxic lung injury (pulmonary vascular permeability, histopathological, and biochemical BALF changes) in rabbits. The effects of lidocaine on more severe lung injury (decreased oxygenation) caused by hyperoxia for 72 h deserve further study.
Takao
Y
Y
Department of Anaesthesiology, Kobe University School of Medicine, Japan.
Mikawa
K
K
Nishina
K
K
Maekawa
N
N
Obara
H
H
D000418:Albumins / Q000032:analysis; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D003165:Complement System Proteins / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D010450:Endopeptidases / Q000378:metabolism; D018496:Hyperoxia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015656:Respiratory Mechanics / Q000187:drug effects
D000418:Albumins; D000779:Anesthetics, Local; D016207:Cytokines; D017382:Reactive Oxygen Species; D003165:Complement System Proteins; D008012:Lidocaine; D010450:Endopeptidases; D010100:Oxygen