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

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.