Intraperitoneal instillation of polihexanide produces hypotension and vasodilation: in vivo and in vitro study in rats.
OBJECTIVE
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 produced 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 (EC(50), 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.


CONCLUSIONS
This implies that polihexanide may promote nitric oxide liberation, potassium channel activation and vasodilation that may result in hypotension.
Frieling
Helge
H
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany. helge.frieling@psych.imed.uni-erlangen.de
Gründling
Matthias
M
Lauer
Kai-Steffen
KS
Wendt
Michael
M
Hachenberg
Thomas
T
Hackenberg
Thomas
T
Lehmann
Christian
C
Pavlovic
Dragan
D
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006586:Hexanes / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced*; D007082:Ileum / Q000098:blood supply; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008297:Male; D008853:Microscopy; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010533:Peritoneal Lavage; D010656:Phenylephrine / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000891:Anti-Infective Agents, Local; D006586:Hexanes; D011108:Polymers; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; C475962:polymeric biguanide polihexanide