Attenuation of intestinal ischemic injury and shock by physostigmine.

Background: Recently, protection in shock (hemorrhagic or septic) by physostigmine has been demonstrated. Here, we studied the protective effect of intravenous infusion of physostigmine in a rat model of severe intestinal ischemia-reperfusion (I/R) injury and shock.

Materials And Methods: Mesenteric I/R was induced in male Wistar rats by occlusion of the superior mesenteric artery (90 min) and subsequent reperfusion (120 min). Physostigmine (30 or 70 μg/kg) was administered as bolus injection before induction of I/R. One additional group received, subsequent to the bolus of 30-μg/kg physostigmine, a continuous infusion of 60-μg/kg physostigmine till the end of the experiment.

Results: Physostigmine at a dose of 70 μg/kg administered before I/R significantly decreased the macroscopically and microscopically visible intestinal damage. In addition to and presumably as a result of this local protective effect, physostigmine prevented shock induced by reperfusion of the ischemically injured intestine. Lower doses (30 μg/kg) or continuous application of physostigmine were less advantageous.

Conclusions: Physostigmine is clearly protective in intestinal I/R injury and shock. However, for this purpose, physostigmine has to be applied at a dose (70 μg/kg), that is, approximately double the amount of the presently used clinical dose.