EFFECT OF THE POTASSIUM CHANNEL OPENER ZM260384 ON SKELETAL-MUSCLE FUNCTION DURING RESTRICTED BLOOD-FLOW IN THE ANESTHETIZED CAT

The aim of the present experiment was to determine whether the potassi um channel opener 4-dihydro-2H-1,4-benzoxazine-4-yl)pyridine-N-oxide ( ZM260384) was capable of accelerating the decline in skeletal muscle f unction during restricted blood flow in vivo. Cats (3.0-4.5 kg body we ight) were anaesthetized with alphaxalone-alphadalone and breathed spo ntaneously following tracheotomy. Isometric tension was measured in th e extensor digitorum longus-anterior tibialis (EDL-TA) muscle group. I schaemia was induced by perfusing the hindlimb with the animal's own b lood at a rate of 12.5 ml min(-1) using a roller pump and stimulating the common peroneal nerve to induce repetitive submaximal tetanic cont ractions in the EDL-TA. The number of stimulation voltage increments r equired each minute to maintain a constant level of submaximal mechani cal output and the time to exhaustion were used as indices of the rare of tension decline. The rare of tension decline in the ischaemic EDL- TA in the presence of ZM260384 at 3 mg kg(-1), a maximally hypotensive dose predicted to be within the dose range required to exert direct e ffects on skeletal muscle, was measured and compared with the rate of tension decline in the presence of ZM260384 at 0.03 mg kg(-1), also a maximally hypotensive dose but below the predicted dose range for skel etal muscle effects. The number of voltage increments per minute was 1 .93 +/- 0.07 and 1.48 +/- 0.14 (P < 0.05) in the presence of 3 and 0.0 3 mg kg(-1) ZM260384, respectively. Time to exhaustion was 17.5 +/- 4. 2 and 7.2 +/- 0.8 min (P < 0.05) in the presence of 3 and 0.03 mg kg(- 1) ZM260384, respectively. Given that there was no difference between these two groups in any haemodynamic variable measured, the results of the present study suggest that ZM260384 (3 mg kg(-1)) increases the r ate of isometric force loss in ischaemic skeletal muscle in vivo.