Does early posttreatment with lidocaine attenuate endotoxin-induced acute injury in rabbits?

BACKGROUND

It is well known that endotoxin causes acute lung injury, resulting in adult respiratory distress syndrome. Lidocaine pretreatment has recently been shown to attenuate endotoxin-induced lung injury in rabbits. The aim of the current study was to determine whether early postinjury treatment with intravenous lidocaine could attenuate acute lung injury induced by endotoxin in rabbits.

METHODS

Thirty-two male anesthetized rabbits were randomly assigned to receive one of four treatments (n = 8 for each group): infusion of saline (group S-S), infusion of saline with lidocaine treatment (group S-L), infusion of Escherichia coli endotoxin (100 micrograms.kg-1 over a 60-min period) without lidocaine treatment (group E-S), or infusion of endotoxin with lidocaine treatment (group E-L). Ten minutes after the end of infusion of endotoxin (groups E-L and E-S) or saline (groups S-S and S-L), the animals received a bolus injection followed by continuous infusion of lidocaine (2 mg.kg-1 + 2 mg.kg-1.h-1 in groups S-L and E-L) or saline (groups S-S and E-S). The rabbits' lungs were ventilated with 40% O2. Hemodynamics, peripheral leukocyte and platelet counts, and arterial O2 tension (PaO2) were recorded during the ventilation period (6 h). After the observation, lung mechanics; the cell fraction of bronchoalveolar lavage fluid (BALF); and concentrations of activated complement components C3a and C5a, cytokines, and arachidonic acid metabolites in BALF were measured and analyzed. The ratio of lung wet weight to dry weight (W/D weight ratio) and albumin concentrations in BALF were analyzed as indexes of pulmonary edema. The Cypridina luciferin analogue-dependent chemiluminescence (representing O2 production) by neutrophils isolated from the pulmonary artery and light-microscopic findings of the lung were compared among the four groups.

RESULTS

Endotoxin caused decreases in peripheral leukocyte and platelet counts, lung compliance, and PaO2. It caused increases in lung W/D weight ratio; polymorphonuclear cell counts in BALF; and albumin, C3a, C5a, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and thromboxane B2 concentrations in BALF. Lidocaine attenuated the changes in W/D weight ratio and morphologic lung damage. The change in compliance, decrease in PaO2, and albumin concentrations in BALF were slightly but significantly less in rabbits receiving lidocaine after injury. The Cypridina luciferin analogue-dependent chemiluminescence by neutrophils was greater in rabbits receiving endotoxin without lidocaine than in those receiving endotoxin with lidocaine.

CONCLUSIONS

These results indicate that early treatment with lidocaine attenuates endotoxin-induced lung edema in rabbits without affecting chemical mediators in BALF. However, the improvement is slight and likely to be of little clinical significance.