Intraperitoneal instillation of polihexanide produces hypotension and vasodilation: In vivo and in vitro study in rats

Background and aims: Treatment of peritonitis may include abdominal lavage with a local disinfectant polihexanide, available as 0.04% solution, which is often accompanied by hypotension. Methods: We examined the effects of peritoneal installation of polihexanide or NaCl 0.9% (10 ml each, for 10 min; polihexanide n=5, NaCl n=5) on mean arterial pressure in healthy rats and, using intravital microscopy, measured in seven other animals the diameter of terminal ileum submucosal arterioles and venules before and after local superfusion with polihexanide. Furthermore, in an in vitro isometric preparation of rat thoracic aortal rings, with and without endothelium, we tested the effects of cumulative concentrations of polihexanide on vascular basic tension and on tension elicited by phenylephrine and KCl. Results: It was found that polihexanide peritoneal instillation produce d a decrease in mean arterial pressure, while superfusion with polihexanide caused local vasodilation of intestinal wall blood vessels. In vitro, polihexanide produced endothelium-dependent relaxation in the preparations pre-contracted with phenylephrine (EC₅₀, polihexanide 0.04% solution 2.53±0.16 vs. 1.36±0.16, n=4, P<0.05; polihexanide 4.02±0.12 vs. 3.21±0.10, n=12, P<0.001;+ vs. - endothelium, respectively; -log g%) which (in aortae +endothelium) could be attenuated by either N(G)-nitro-L-arginine methyl ester, a nitric oxide generation inhibitor, or 1H-(1,2,4)oxodiazolo-(4,3-a)quinoxalin-1-one, an inhibitor of guanylyl cyclase. The relaxing effect of polihexanide (aortae -endothelium) was not affected by K⁺-channel blocking agents charybdotoxin, tetraethylammoniumchloride, glibenclamide or 4-aminopyridine, while polihexanide had no effects on 40-mM KCl contractions. Conclusion: This implies that polihexanide may promote nitric oxide liberation, potassium channel activation and vasodilation that may result in hypotension.