Role of K+(ATP) channels in diaphragmatic fatigue in the pig

We infused cromakalim, a K+ATP-sensitive channel opener (80microg(kg as a bolus, followed by 1 microg/kg/min, drop by drop infusion) into 15 anaesthetised, mechanically ventilated, indomethacin-treated pigs. In six of these animals, 120 min after hypotension had been evoked by cromakalim, glibenclamide (10 mg/kg), a K+ATP-sensitive channel antagonist, was administered i.v. over 5 min. The vascular variables and the fatigue of the diaphragm evaluated as Pdi obtained during stimulus strength and endurance test were recorded 120 min after hypotension (control time) and 5, 10, 20 and 30 min later. Cromakalim that induced a stable systemic hypotension did not modify diaphragmatic activity. Glibenclamide decline the transdiaphragmatic pressure during contractions of the diaphragm obtained with different frequencies of phrenic nerve stimulation and changed the response in the endurance test. Glibenclamide chenges the Pdi,max and half-relaxation time of a single contraction obtained immediately after the endurance test. Glibenclamide reversed the hypotensivee effects of cromakalim. Our data indicate that K+ATP-sensitive channels are involved in diaphragmatic activity and are important in delaying the appearance of fatigue.