THE EFFECTS OF GLIBENCLAMIDE, A BLOCKER OF K-SENSITIVE POTASSIUM CHANNELS, ON DIAPHRAGMATIC FATIGUE DURING ENDOTOXEMIA IN PIGS( ATP)

An in vivo porcine model of endotoxaemia was used to study the effects of glibenclamide, a K(+)ATP-sensitive potassium channel blocker. Esch erichia coli lipopolysaccharides (LPS, 70 mu g/kg, i.v., as a bolus) w ere infused into anaesthetized, mechanically ventilated, indomethacin- treated pigs. After 120 min of endotoxaemia, glibenclamide was adminis tered (10 mg/kg, i.v., over 5 min) to half the pigs. The strength at d ifferent frequencies of stimulation (10, 20, 30, 50 Hz, 20 V, 1 s) and the endurance capacity (10 Hz, 20 V, 30 s) of the diaphragm were eval uated after 120 min of endotoxaemia and 5, 10, 20 and 30 min after dru g infusion. Glibenclamide transiently increased the blood pressure wit hout changing the decreased cardiac output and at the same time furthe r impaired the diaphragmatic activity. The reduced ability of the diap hragm to generate force in response to different electrical stimulatio ns was shown by a significant reduction in strength. The endurance ind ex decreased 5 min after glibenclamide infusion, returning to the pre- glibenclamide values by 150 min. These results indicate that glibencla mide modifies the activity of vascular smooth muscle and of the diaphr agm.