Cardiovascular Responses to Glibenclamide During Endotoxaemia in the Pig

Vanelli, G., Hussain, S.N.A., Dimori, M. and Aguggini, G., 1996. Cardiovascular responses to glibenclamide during endotoxaemia in the pig. Veterinary Research Communications, 21(3), 187-200The effects of blockading the ATP-sensitive potassium channel (K+ATP channels) on endotoxin-induced vascular derangements was studied. Escherichia coli endotoxin was infused (20 µg/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 min. The cardiovascular parameters were recorded before (control), every 30 min up to 150 min during endotoxaemia, and then at 5, 15 and 30 min after administration of glibenclamide. Infusion of endotoxin reduced the systemic arterial pressure to 60.6% ± 3.7% (p < 0.01) and increased the pulmonary arterial pressure by 75.9% ± 11.0% (p < 0.01) of the control values. Within 5 min, infusion of glibenclamide transiently 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 influence the cardiac output. Within 30 min, the cardiovascular parameters had returned to the values induced by endotoxin, except for the systemic vascular resistance. Infusion of glibenclamide into normal pigs did not change the systemic pressure or resistance, but the pulmonary pressure and resistance were augmented transiently. These data suggest that, in pigs, the ATP-sensitive K+ channels may be one factor playing a role in the vascular changes due to endotoxaemia, especially in the systemic circulation.     

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 g/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 steength 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.Abbreviations BP blood pressure - CO cardiac output - LPS lipopolysaccharides - Glib glibenclamide - i.m. intramuscular - i.v. intravenous - SEM standard error of the mean - v/v volume/volume P _ab, abdominal pressure - P _di transdiaphragmatic pressure - P _oes oesophageal pressure     

Unusual response of anaesthetised pigs to asphyxia

The effects of vagosympathectomy, asphyxia, hypoxia and hypercapnia on the breathing of anaesthetised pigs are described. Vagosympathectomy caused changes in cardiovascular variables and in the pattern of breathing characteristic of the loss of stretch receptor activity. After vagosympathectomy the linear relationship between tI and tE was abolished. Hypoxia in intact animals produced changes in minute ventilation by peripheral chemoreceptor drive. When this drive was removed by vagosympathectomy the central depressing effects of hypoxia were revealed as a slowing of breathing and reduction in minute volume. The central depressing effect of hypoxia on respiration was very potent in the pig and very clearly seen in asphyxia. Vagosympathectomy caused a reduction in frequency of breathing and respiratory arrest occurred when a dead space of only moderate size was used. Breathing slowed from the moment of connection of the dead space to produce respiratory arrest within 2 min. The pig lung has been considered similar to the human lung on morphometric and physiological grounds but these results show that there are very important species differences in response to asphyxia.