Lidocaine and structure-related mexiletine induce similar contractility-enhancing effects in ischaemia-reperfusion injured equine intestinal smooth muscle in vitro. 2013

Karen Tappenbeck, and Susanne Hoppe, and Klaus Hopster, and Manfred Kietzmann, and Karsten Feige, and Korinna Huber
Department of Physiology, University of Veterinary Medicine, Bischofsholer Damm 15, D-30173 Hannover, Germany.

Postoperative ileus (POI) is a severe complication following small intestinal surgery in horses. It was hypothesised that prokinetic effects of lidocaine, the most commonly chosen drug for treatment of POI, resulted from drug integration into smooth muscle (SM) cell membranes, thereby modulating cell membrane properties. This would probably depend on the structural and lipophilic characteristics of lidocaine. To assess the influence of molecular structure and lipophilicity on prokinetic effects in vitro, the current study compared the effects of lidocaine with four structure-related drugs, namely, mexiletine, bupivacaine, tetracaine and procaine. The response to cumulative drug administration and reversibility of effects were tested by measuring isometric contractile performance of equine jejunal circular SM strips, challenged by a standardised, artificial in vivo ischaemia-reperfusion injury. A second set of SM strips were incubated with the different drugs to determine changes in creatine kinase (CK) release. All drugs caused a drug-specific increase in contractility, although only lidocaine and mexiletine induced similar concentration-dependent curve progressions, significantly reduced CK release, and featured shorter recovery times of tissue contractility after washing, compared to bupivacaine and tetracaine. In was concluded that the structural and lipophilic similarity of mexiletine and lidocaine were responsible for the similar effects of these drugs on SM contractility and cell membrane permeability, which supported the hypothesis that prokinetic effects of lidocaine are based on interactions with SM cell membranes modulated by these features.

UI MeSH Term Description Entries
D007422 Intestines The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE. Intestine
D008012 Lidocaine A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE. Lignocaine,2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide,2-2EtN-2MePhAcN,Dalcaine,Lidocaine Carbonate,Lidocaine Carbonate (2:1),Lidocaine Hydrocarbonate,Lidocaine Hydrochloride,Lidocaine Monoacetate,Lidocaine Monohydrochloride,Lidocaine Monohydrochloride, Monohydrate,Lidocaine Sulfate (1:1),Octocaine,Xylesthesin,Xylocaine,Xylocitin,Xyloneural
D008297 Male Males
D008801 Mexiletine Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties. KO-1173,KO1173,KOE-1173,Mexiletene,Mexiletine Hydrochloride,Mexitil,Mexitil PL,Mexityl,Novo-Mexiletine,KO 1173,KOE 1173,KOE1173,Novo Mexiletine
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D003402 Creatine Kinase A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. Creatine Phosphokinase,ADP Phosphocreatine Phosphotransferase,ATP Creatine Phosphotransferase,Macro-Creatine Kinase,Creatine Phosphotransferase, ATP,Kinase, Creatine,Macro Creatine Kinase,Phosphocreatine Phosphotransferase, ADP,Phosphokinase, Creatine,Phosphotransferase, ADP Phosphocreatine,Phosphotransferase, ATP Creatine
D006736 Horses Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest. Equus caballus,Equus przewalskii,Horse, Domestic,Domestic Horse,Domestic Horses,Horse,Horses, Domestic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015427 Reperfusion Injury Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA. Ischemia-Reperfusion Injury,Injury, Ischemia-Reperfusion,Injury, Reperfusion,Reperfusion Damage,Damage, Reperfusion,Injury, Ischemia Reperfusion,Ischemia Reperfusion Injury,Ischemia-Reperfusion Injuries,Reperfusion Damages,Reperfusion Injuries

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