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.

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.