Effect of the potassium channel opener ZM260384 on skeletal muscle function during restricted blood flow in the anaesthetized cat

Abstract

SUMMARYThe aim of the present experiment was to determine whether the potassium channel opener 2-(2,2-bis(difluoromethyl)-6-nitro-3,4-dihydro-2H-1,4-benzoxazine-4-yl)pyridine-N-oxide (ZM260384) was capable of' accelerating the decline in skeletal muscle function during restricted blood flow in vivo. Cats (3.0-4.5 kg body weight) were anaesthetized with alphaxalone-alphadalone and breathed spontaneously following tracheotomy. Isometric tension was measured in the extensor digitorum longus-anterior tibialis (EDL-TA) muscle group. Ischaemia was induced by perfusing the hindlimb with the animal's own blood at a rate of 12 5 ml min' using a roller pump and stimulating the common peroneal nerve to induce repetitive submaximal tetanic contractions in the EDL-TA. The number of stimulation voltage increments required each minute to maintain a constant level of submaximal mechanical output and the time to exhaustion were used as indices of the rate of tension decline. The rate of tension decline in the ischaemic EDL-TA in the presence of ZM260384 at 3 mg kg-', a maximally hypotensive dose predicted to be within the dose range required to exert direct effects on skeletal muscle, was measured and compared with the rate of tension decline in the presence of ZM260384 at 0 03 mg kg-', also a maximally hypotensive dose but below the predicted dose range for skeletal 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 0-03 mg kg 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 003 mg kg-IZM260384, 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 ') increases the rate of isometric force loss in ischaemic skeletal muscle in vivo.

Cats in Scientific Procedures: Main Areas of Use in the UK and Some Causes for Concern

“…Three papers on work involving cats were published in the area of applied immunology, each studying the epidemiology of a different parasitic infection affecting both cats and humans. A single publication, which was categorised as applied musculoskeletal research, described work on 23 terminally anaesthetised, mature male cats to observe the effects of a potassium channel opener on skeletal muscle function (14).…”

Carbocation Organocatalysis in Interrupted Povarov Reactions to cis‐Fused Pyrano‐ and Furanobenzodihydropyrans

“…Benzodihydropyran (BDHP) skeletons ( A , Scheme ) are recognized as privileged substructures pivotal in bioactive molecules and drug discovery Compounds containing a BDHP core feature a natural product‐like scaffold and have high potential in effective drug‐like molecular entities in both biological and synthetic, explorations. Constructions of the BDHP core by formal [4+2] cycloadditions have shown step‐economic routes through reactions of dienophiles with ortho ‐quinone methide (Scheme a) or with oxocarbenium (Scheme b).…”