The effects of glibenclamide, a blocker of K+ ATP-sensitive potassium channels, on diaphragmatic fatigue during endotoxaemia in pigs.
An in vivo porcine model of endotoxaemia was used to study the effects of glibenclamide, a K+ ATP-sensitive potassium channel blocker. Escherichia coli lipopolysaccharides (LPS, 70 micrograms/kg, i.v., as a bolus) were infused into anaesthetized, mechanically ventilated, indomethacin-treated pigs. After 120 min of endotoxaemia, glibenclamide was administered (10 mg/kg, i.v., over 5 min) to half the pigs. The strength at different 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 evaluated after 120 min of endotoxaemia and 5, 10, 20 and 30 min after drug infusion. Glibenclamide transiently increased the blood pressure without changing the decreased cardiac output and at the same time further impaired the diaphragmatic activity. The reduced ability of the diaphragm to generate force in response to different electrical stimulations was shown by a significant reduction in strength. The endurance index decreased 5 min after glibenclamide infusion, returning to the pre-glibenclamide values by 150 min. These results indicate that glibenclamide modifies the activity of vascular smooth muscle and of the diaphragm.
Aguggini
G
G
Institute of Veterinary Physiology and Biochemistry, University of Milan, Italy.
Dimori
M
M
Vanelli
G
G
Albertini
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003964:Diaphragm / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D004558:Electric Stimulation; D004731:Endotoxins / Q000097:blood; D005260:Female; D005905:Glyburide / Q000494:pharmacology* / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018763:Muscle Fatigue / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D010791:Phrenic Nerve / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D013553:Swine Diseases / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D013997:Time Factors; D014115:Toxemia / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary*
D004731:Endotoxins; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005905:Glyburide