Current progress in the studies of myocardial membrane alterations during
endotoxin shock indicates that
endotoxin administration impairs (Na(+) + K(+)-
ATPase enzyme system by disrupting the coordination of the
ouabain receptor subunit and the catalytic subunit of the
enzyme system, and that the disruption is due to an alteration in the
lipid microenvironment and a decrease in the phosphorylated intermediate of the
enzyme cycle. Studies of the
membrane lipid profile provide evidence that
endotoxin administration modifies the molecular structure of cardiac
membrane lipids in association with the activation of
phospholipases A1 and A2 and with the inhibition of
phospholipid methylating
enzymes. Using
liposomes as a membrane model for investigation,
endotoxin was found to be capable of modifying the physical property of membrane
phospholipids by altering the molecular packing and the phase transition temperature of
lipid bilayers. Further studies with Na(+)-Ca2+ exchange system in cardiac sarcolemma have established the roles of
phospholipase A2 and
protein phosphorylation on the
endotoxin-induced derangement in myocardial Na(+)-Ca2+ exchange. Based on these studies, it is concluded that
endotoxin administration exerts
multiple injuries in different membrane-associated
enzyme/receptor systems and that the mechanisms responsible for the
endotoxin-induced membrane damage can be categorized into two conceptual frameworks: namely, changes in
membrane lipid microenvironment in response to
phospholipase A activation and alterations in the phosphorylation of the
enzyme/receptor
proteins.