CARDIOVASCULAR-RESPONSES TO GLIBENCLAMIDE DURING ENDOTOXEMIA IN THE PIG

The effects of blockading the ATP-sensitive potassium channel (K-ATP() channels) on endotoxin-induced vascular derangements was studied. Es cherichia coli endotoxin was infused (20 mu g/kg per h) intravenously for 180 min into anaesthetized, mechanically ventilated, indomethacin- treated pigs. After 150 min of endotoxaemia, glibenclamide (a K-ATP(+) channel blocker) was infused intravenously at 2 mg/kg per min for 5 m in. The cardiovascular parameters were recorded before (control), ever y 30 min up to 150 min during endotoxaemia, and then at 5, 15 and 30 m in after administration of glibenclamide. Infusion of endotoxin reduce d the systemic arterial pressure to 60.6% +/- 3.7% (p < 0.01) and incr eased the pulmonary arterial pressure by 75.9% +/- 11.0% (p < 0.01) of the control values. Within 5 min, infusion of glibenclamide transient ly but significantly reversed the systemic hypotension by raising the systemic vascular resistance, whereas the increased pulmonary arterial pressure was further augmented. Glibenclamide infusion did not influe nce the cardiac output. Within 30 min, the cardiovascular parameters h ad returned to the values induced by endotoxin, except for the systemi c vascular resistance. Infusion of glibenclamide into normal pigs did not change the systemic pressure or resistance, but the pulmonary pres sure and resistance were augmented transiently. These data suggest tha t, in pigs, the ATP-sensitive K+ channels may be one factor playing a role in the vascular changes due to endotoxaemia, especially in the sy stemic circulation.