In vitro analysed effects of two different in vivo administered lidocaine dosageson the equine jejunal smooth muscle challenged by an ischemia-reperfusion-injury-model (IRIM)

Abstract

SummaryLidocaine as a prokinetic drug is acting dose-dependently on the ischemia-reperfusion (IR) injured equine jejunal smooth muscle. The aim of the study was to examine the effects of different dosages of lidocaine on jejunal smooth muscle contractility in vitro as a basic research approach to examine the potential mechanism of lidocaine. Sustainability of this in vivo effect of applied lidocaine was tested under in vitro conditions. Hypothesis: Application of a higher initial dose of lidocaine during IR in vivo could change, improve or even impair the contractility effects on jejunal smooth muscle in vitro. 12 horses received either a 1.3 mg/kg (IRL1; N = 7) or 2.6 mg/kg (IRL2; N = 5) lidocaine bolus infusion over 10 minutes followed by 0.05 mg/kg/min intravenously for 5 minutes while artificial IR injury on the jejunum was induced. To examine the effects of lidocaine on jejunal smooth muscle function, isometric force performance (amplitude, frequency and contractility) was measured in vitro at two different times (t1,t2). The influence of either in vitro lidocaine supplementation (KHB+L) or no supplementation (KHB) was studied to assess the sustainability of lidocaine effects. IRL2 KHB+L showed a significant higher frequency of contraction at t2 compared to IRL1KHB+L. Amplitude of contractions and contractility were significantly decreased in the IRL1 KHB tissues compared to IRL1 KHB+L at t2. The IRL2 KHB tissues at t2 showed a significant decrease of frequency and amplitude of contractions compared to the IRL2 KHB+L. There was a significant decrease in frequency and an increase in amplitude of contractions and in contractility in IRL 1 KHB+L from t1 to t2. In IRL1 KHB a significant decrease in frequency was observed but increase in amplitude of contractions and contractility was lacking from t1 to t2. IRL2 KHB expressed a significant decrease in frequency and a significant increase in amplitude from t1 to t2, while amplitude, frequency and contractility in IRL2 KHB+L were not influenced by time. High dosage lidocaine bolus infusion with further supplementation increased frequency of contractions and maintained amplitude of contractions over the experimental time. This in vitro study suggested that immediate application of a high bolus dosage may improve protective effects of lidocaine furthermore in vitro. At the moment, no pharmacokinetic data for a 2.6 mg/kg over 10 min. lidocaine bolus in vivo is available. Recommending a higher initial lidocaine bolus in vivo, especially because of negative side effects, requires further investigation.Keywords: lidocaine / equine jejunum / contractility / smooth muscle / prokinetic effects / anesthesiology / horse In vitro untersuchte Effekte von zwei unterschiedlichen in vivo verabreichten Lidokaindosierungen auf die glatte Muskulatur des equinen Jejunums in einem Ischämie-Reperfusions-Modell Lidokain wirkt dosisabhängig prokinetisch auf die Ischämie-Reperfusion (IR) geschädigte glatte Muskulatur des equinen Jejunums. Ziel dieser Studie war, die Effekte unterschiedlic...