CROMAKALIM DOES NOT PROTECT AGAINST SKELETAL-MUSCLE FATIGUE IN AN ANESTHETIZED RAT MODEL OF ACUTE HINDLIMB ISCHEMIA

The effects of the potassium (K+) channel opener, cromakalim, on skele tal muscle performance were studied in a model of acute hindlimb ischa emia in the anaesthetized rat. Twitch contractions to direct electrica l stimulation of the extensor digitorum and tibialis anterior skeletal muscles were recorded following administration of cromakalim (10-100 mu g kg-1 i.v.) under normal and reduced whole limb blood flow. With n ormal blood flow, twitch responses (0.5 and 1 Hz) of the hindlimb skel etal muscles were sustained for > 30 min. Controlled adjustment of the perfusion pressure in the contralateral hindlimb to 45, 30 or 0 mm Hg by partial or total occlusion of the abdominal aorta produced a press ure-related fall in flow to the working hindlimb, and a corresponding increase in the rate of muscle fatigue. Cromakalim (10-100 mug kg-1 i. v.) produced dose-dependent reduction in mean carotid arterial blood p ressure, femoral arterial pressure and hindlimb vascular resistance to gether with an increase in iliac artery blood flow and heart rate, but did not attenuate skeletal muscle fatigue under the different conditi ons of muscle work and ischaemia employed. A similar profile was obser ved with levcromakalim (15 mug kg-1 i.v), the active enantiomer of cro makalim. These results demonstrate that in the direct muscle-stimulate d hindlimb of the anaesthetized rat, the K+ channel opener cromakalim does not prevent acute ischaemia-induced skeletal muscle fatigue. The previous observation that K+ channel openers improve nutritive blood f low in a chronic model of rat hindlimb ischaemia is not reflected by a n improvement in muscle function in the present study.