monensin and Shock--Septic

Although a linkage between aerobic glycolysis and sodium-potassium transport has been demonstrated in diaphragm, vascular smooth muscle, and other cells, it is not known whether this linkage occurs in skeletal muscle generally. Metabolism of intact hind-leg muscles from young rats was studied in vitro under aerobic incubation conditions. When sodium influx into rat extensor digitorum longus (EDL) and soleus muscles was facilitated by the sodium ionophore monensin, muscle weight gain and production of lactate and alanine were markedly stimulated in a dose-dependent manner. Although lactate production rose in both muscles, it was more pronounced in EDL than in soleus. Monensin-induced lactate production was inhibited by ouabain or by incubation in sodium-free medium. Preincubation in potassium-free medium followed by potassium re-addition also stimulated ouabain-inhibitable lactate release. Replacement of glucose in the incubation medium with pyruvate abolished monensin-induced lactate production but exacerbated monensin-induced weight gain. Muscles from septic or endotoxin-treated rats exhibited an increased rate of lactate production in vitro that was partially inhibited by ouabain. Increases muscle lactate production in sepsis may reflect linked increases in activity of the Na+, K+-ATPase, consumption of ATP and stimulation of aerobic glycolysis.

Topics: Aerobiosis; Alanine; Amino Acids; Animals; Dose-Response Relationship, Drug; Glucose; Glutamic Acid; Glycolysis; Hindlimb; Hydrogen-Ion Concentration; Lactic Acid; Lipopolysaccharides; Male; Monensin; Muscle, Skeletal; Ouabain; Potassium; Pyruvic Acid; Rats; Rats, Sprague-Dawley; Shock, Septic; Sodium; Sodium-Potassium-Exchanging ATPase

The present investigation was carried out in anesthetized dogs to compare the cardiovascular effects of dopamine and monensin, a carboxylic ionophore, in normal and E coli endotoxin-induced shock conditions. In control animals, monensin increased cardiac contractility, cardiac output, systemic blood pressure, and coronary blood flow in a dose-dependent manner, but had little or no effect on heart rate. However, unlike dopamine, which selectively increased renal blood flow, monensin did not affect renal blood flow in doses that produced a maximal increase in coronary blood flow or other hemodynamic effects. The duration of action of monensin was longer than 2 hr. Both dopamine and monensin reversed the cardiac depression and hypotension produced by E coli endotoxin, and in these experiments also, the duration of action of monensin was longer than 2 hr. Regional blood flow measurements with the radioactive microsphere (15 mu) technique demonstrated a marked decrease in organ blood flows at 60 min postendotoxin, but some recovery was observed at 90 min. In the left ventricle, reduction of flow to the endocardial region was greater than to the epicardium. In dogs with endotoxic shock, monensin produced a significant increase in organ blood flows towards or even above control values.

Topics: Animals; Blood Pressure; Cardiac Output; Coronary Circulation; Dogs; Dopamine; Escherichia coli Infections; Furans; Hemodynamics; Monensin; Myocardial Contraction; Regional Blood Flow; Renal Circulation; Shock, Septic; Stimulation, Chemical

The haemodynamic effects of the carboxylic ionophore monensin have been examined in cats anaesthetized with sodium pentobarbitone. Marked increases in left ventricular dP/dtmax (and dP/dt at fixed isovolumic pressures) and slight increases in cardiac output and stroke volume occurred, indicating increased myocardial contractility. Heart rate was unchanged but systemic arterial pressure was substantially increased. Satisfactory increases in contractility and arterial pressure were obtained when monensin was infused intravenously in a total dose of 0.25 mg kg-1 over 10 min. Larger doses, especially if rapidly injected, resulted in very marked increases in myocardial contractility leading eventually to cardiac failure. The haemodynamic effects of monensin were markedly reduced during shock induced by E. coli endotoxin and there was unfortunately no evidence to suggest that this extremely potent compound might be potentially beneficial in this form of profound cardiovascular shock.

Topics: Animals; Cats; Endotoxins; Escherichia coli; Female; Furans; Hemodynamics; Male; Monensin; Shock, Septic; Time Factors