COMPARISON OF THE PROTECTIVE EFFECTS OF GLUCOSE METABOLISM AND OPIOID PRECONDITIONING AGAINST HYPOXIC DAMAGE IN SWINE SKELETAL MUSCLE

Abstract

Pharmacological preconditioning by opioid receptor activation, as a means to prevent or attenuate ischemic damage of both cardiac and skeletal muscle, has been reported. 1,8,53-55 In general, it is believed that this protection is conferred by subsequent activation of protein kinase C and opening of ATP dependent potassium channels. Another reported modality of protecting muscle from ischemia relies on increasing glucose oxidation through pharmacological means. Since both modalities of protection rely ultimately on increased postischemic ATP levels, we hypothesized that preconditioning by either method would result in similar preservation of posthypoxic muscle force. Swine skeletal muscle bundles were therefore pretreated with either [DPen 2,5]-enkephalin (DPDPE), a δ 1-selective opioid receptor agonist (N=24), or the pyruvate dehydrogenase activator dichloroacetate (DCA) (N=8). The muscle bundles were then exposed to 90 min of hypoxia and then reoxygenated for 120 min. Stimulated twitch forces were recorded throughout to provide functional assessment of the bundles. The muscle bundles pretreated with DPDPE maintained higher mean peak twitch forces compared to controls both at the end of hypoxia and during early reoxygenation (P < 0.05). In comparison, those treated with DCA had similar mean values compared to control throughout the duration of the protocol. These results suggest that metabolic pretreatment with DCA did not confer the same degree of protection that opioid pretreatment with DPDPE provided during hypoxia and early reoxygenation.