Myocardial Protection by Monophosphoryl Lipid A: Potential Mechanisms

Xi, Lei; Heß, Michael; Kukreja, Rakesh C.

doi:10.1111/j.1527-3466.1999.tb00019.x

Cited by 2 publications

(4 citation statements)

References 85 publications

(134 reference statements)

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“…The beneficial effects of MLA have been used in inducing tolerance to endotoxemia in both laboratory animals and humans, in immunotherapy or immunoprophylaxis, as an adjuvant for many vaccines, in inducing delayed protection against cerebral vasospasm caused by subarachnoid hemorrhage, and for delayed cardioprotection through complex mechanisms. 26 In the present study, MLA ( S. typhimurium SL684, Rc mutant) containing “monophosphoryl residue” did not attenuate ischemia–reperfusion arrhythmias. Monophosphoryl lipid A used in this and previous studies had both “the mono and the diphosphoryl residues” (Re595 R mutant).…”

Section: Discussionmentioning

confidence: 44%

“… 22 - 24 Among various mediators, particular interest has focused on nitric oxide which has also been implicated in the antiarrhythmic and cardioprotective effects of preconditioning against ischemia and can also be inhibited by dexamethasone. 25 , 26 Despite the fact that L-NAME, a nitric oxide synthase inhibitor that inhibits both the constitutive (cNOS) and inducible (iNOS) versions of the enzyme, it failed to change the number or severity of ischemia or reperfusion arrhythmias in anesthetized rats. 14 In previous studies, by using intracellular recording methods, it was shown that atria obtained from LPS-treated rats had prolonged action potential duration.…”

Section: Discussionmentioning

confidence: 99%

“…Monophosphoryl lipid A used in this and previous studies had both “the mono and the diphosphoryl residues” (Re595 R mutant). 8 , 26 In this study, it was determined that diphosphoryl groups, subcomponent composition, were necessary or responsible for the antiarrhythmic effect of MLA. The antiarrhythmic effect of both LPS and MLA is explained with iNOS activation, 1 , 2 and diphosphoryl residue is necessary for this antiarrhythmic effect.…”

Section: Discussionmentioning

confidence: 99%

“…Monophosphoryl lipid A’s positive benefits have also been used in cardioprotection, which uses complicated processes to prevent ischemia–reperfusion arrhythmias. 26 Monophosphoryl lipid A could be a promising candidate for prophylaxis of arrhythmias after myocardial infarction.…”

Section: Discussionmentioning

confidence: 99%

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The Effects of Lipopolysaccharide Derivatives in Rodent Models of Cardiac Arrhythmia

Yılmaz¹,

Boz²,

İskit³

2022

The Anatolian Journal of Cardiology

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Background: Several previous studies have suggested that sublethal doses of Escherichia coli lipopolysaccharide (endotoxin) and monophosphoryl lipid A Re595, a non-pyrogenic derivative of Salmonella minnesota lipopolysaccharide, exhibit antiarrhythmic effects in the rat model of ischemia–reperfusion arrhythmias. Methods: 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. Results: 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. Conclusion: 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.

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Section: Discussionmentioning

confidence: 44%