The Effects of Lipopolysaccharide Derivatives in Rodent Models of Cardiac Arrhythmia.

Abstract

Several previous studies have suggested that sublethal doses of Escherichia coli lipopolysaccharide (endotoxin) and monophosphoryl lipid A Re595, a nonpyrogenic derivative of Salmonella minnesota lipopolysaccharide, exhibit antiarrhythmic effects in the rat model of ischemia-reperfusion arrhythmias. In this study, the protective effect of lipopolysaccharide derivatives was also further investigated in drug (aconitine or ouabain)-induced arrhythmia models, and conclusions were drawn with particular emphasis on the molecular characteristics of different types of lipopolysaccharide. The importance of the molecular structure for the antiarrhythmic effect of monophosphoryl lipid A and E. coli lipopolysaccharide was tested in the ischemia-reperfusion arrhythmia model. In contrast to monophosphoryl lipid A from Salmonella typhimurium SL 684 which has only monophosphoryl residue in its structure, monophosphoryl lipid A Re595, obtained from S. minnesota, and E. coli lipopolysaccharide which have both mono and diphosphoryl residue reduced the duration of ventricular tachycardia (e.g., during reperfusion: vehicle: 176 ± 22.8; monophosphoryl lipid A Re595: 132.83 ± 12.1, as second, n=8-10, P < .05) and the incidence of ventricular fibrillation. The antiarrhythmic effects of E. coli lipopolysaccharide and monophosphoryl lipid A Re595 in ischemia-reperfusion arrhythmia model were absent in either aconitine- (e.g., onset time for ventricular ectopic beats: saline 25.3 5.0, E. coli lipopolysaccharide 24.3 ± 7.1; vehicle: 24.0 ± 4.5, monophosphoryl lipid A SL684 23.8 ± 4.3, as second, n=6, P > .05) or ouabain-induced arrhythmia models in mice. Therefore, we conclude that lipopolysaccharide derivatives exhibit antiarrhythmic effect only in ischemia-reperfusion arrhythmias, and lipopolysaccharide should possess diphosphoryl groups in its subcomponent composition for this antiarrhythmic effect.