Effect of lidocaine pretreatment on endotoxin-induced lung injury in rabbits.
BACKGROUND
It is well known that endotoxin causes acute lung injury resulting in adult respiratory distress syndrome. Numerous cellular and humoral factors such as macrophages, neutrophils, platelets, and inflammatory mediators (e.g., activated complements, cytokines, and arachidonic acid metabolites) are thought to play a pivotal role in the pathogenesis of endotoxin-induced lung injury. Furthermore, pulmonary edema in acute lung injury is associated with an increase in vascular permeability that may arise from a perturbation of the endothelial cell surface membrane. Lidocaine has been shown to inhibit function of these cells and stabilize cell membranes. The aim of the current study was to determine whether pretreatment with intravenous lidocaine could attenuate acute lung injury induced by endotoxin in rabbits.


METHODS
Twenty-seven anesthetized male rabbits were randomly assigned to receive one of three treatments (n = 9 for each group); infusion of saline (as a control), infusion of Escherichia coli endotoxin (30 micrograms kg-1 over a 60-min period) without treatment with lidocaine, and infusion of endotoxin with treatment with lidocaine. A single dose of intravenous lidocaine 2 mg.kg-1 was administered 10 min before infusion of endotoxin and thereafter infused at a rate of 2 mg.kg-1.h-1 until 6 h after the start of endotoxin administration, when the animals were killed. The lungs of the rabbits were ventilated with 40% oxygen. Hemodynamics, peripheral leukocytes counts, and arterial oxygen tension were recorded during the ventilation period. After the observation, lung mechanics, cell fraction of bronchoalveolar lavage fluid (BALF), activated complements, cytokines, and arachidonic acid metabolites concentrations in BALF were measured and analyzed. The lung wet-to-dry-weight ratio and albumin concentrations in BALF were analyzed as an indices of pulmonary edema. The cypridina luciferin analog-dependent chemiluminescence (representing superoxide production) by neutrophils isolated from the pulmonary artery and light microscopic findings were compared among the three groups.


RESULTS
Endotoxin caused decreases in peripheral leukocyte counts, lung compliance, and arterial oxygen tension, and increases in the lung wet-to dry-weight ratio, polymorphonuclear cell counts in BALF, and albumin, C3a, C5a, tumor necrosis factor alpha, interleukin-1 beta, and thromboxane B2 concentrations in BALF. Lidocaine pretreatment attenuated these changes. The cypridina luciferin analog--dependent chemiluminescence was greater in rabbits receiving endotoxin than in the control. Lidocaine pretreatment attenuated the increase in chemiluminescence. Endotoxin caused extensive morphologic lung damage, which was lessened by lidocaine.


CONCLUSIONS
These results suggest that intravenous lidocaine pretreatment has a prophylactic effect on endotoxin-induced lung injury in rabbits. However, further studies are required to investigate the therapeutic (as an early posttreatment) effect of the drug given after lung injury because rabbits in the current study received lidocaine before endotoxemia.
Mikawa
K
K
Department of Anaesthesiology, Kobe University School of Medicine, Japan.
Maekawa
N
N
Nishina
K
K
Takao
Y
Y
Yaku
H
H
Obara
H
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000187:drug effects; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008012:Lidocaine / Q000097:blood / Q000627:therapeutic use*; D008163:Luminescent Measurements; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D015656:Respiratory Mechanics / Q000187:drug effects; D013997:Time Factors
D004731:Endotoxins; C044101:endotoxin, Escherichia coli; D008012:Lidocaine; D010100:Oxygen