Effects of selective and non-selective NSAIDs on in vitro contractility of the equine jejunum

Abstract

NSAIDs are commonly used in colic therapy. Especially in the post-operative stage, dysmotility is a severe complication. Literature provides evidence of an effect on the contractility of the gastrointestinal tract through NSAIDs. Therefore, the aim of this study was to investigate the effects of NSAIDs on the equine small intestine and, in particular, to accurately examine the effects on the injured intestine. Included were horses with a healthy intestine which had been subject to a median laparotomy with two consecutive experimental ischemias and reperfusions. In the first experiment, an in vitro application of the NSAIDs flunixin and firocoxib was carried out. In the second experiment, the respective NSAID was administered to the probands in vivo and the samples were examined by means of a measurement of the contractility in vitro. The in vitro application of the non-selective COX inhibitor flunixin had significant inhibitory effects on the contractility of the equine jejunum in vitro. These inhibitory effects occurred in comparison to all other samples. In vitro application of firocoxib had no significant effects on the contractility in vitro but showed a slight insignificant increasing effect, especially on the frequency of contractions of the circular musculature. After intravenous in vivo application, subsequent sample taking and examination, the results of the measurements of contractility in vitro were clearly more heterogenous. This, for example, led to a significant increase in frequency of contractions of the longitudinal musculature of the samples, damaged by ischemia and reperfusion, after intravenous application of flunixin, and to a significantly higher amplitude of contractions of the longitudinal musculature of the samples, damaged by ischemia and reperfusion, after intravenous application of firocoxib. These inconsistent effects and the deviations to the effects after in vitro application probably indicate a toxicological effect after in vitro application of the agents and an altered initial situation in the second experiment due to a panenteric occurrence (resulting from previous damage through the first experiment). The explanation would be an overdosage and, therefore, an intoxication of the tissue after in vitro application of the agents because the inhibitory effects of flunixin only occurred in high concentrations. Based on the examinations of the current study, significant differences between the in vitro application of flunixin and firocoxib on the in vitro contractility of the equine jejunum could be determined. The inhibitory effects of flunixin were dependent on its concentration and only appeared in high concentrations (2.7 × 10-5M). Although the dosages applied in vitro, were oriented towards plasma concentrations of the agents after intravenous application or concentrations used in other studies, it was not clear whether these concentrations corresponded to the actually reached tissue concentrations after intravenous or oral application of the agents. Due to high plasma protein bindings, the actual tissue concentration after intravenous or oral application could be much lower. In the current study, also merely the in vitro contractility was examined and conclusions regarding in vivo motility could not be drawn absolutely. The clinical relevance of the inhibitory effect of flunixin on the contractility in vitro after in vitro application cannot be estimated due to the current study. Also it is not clear to which extent the type of application (in vitro application and intravenous in vivo application) actually had an influence on the results. In the future, studies have to follow that examine the effects of selective and non-selective NSAIDs on the contractility and motility of the equine intestine after intravenous in vivo application, in order to support the choice of an adequate NSAID, especially in post-operative therapy after colic surgery.