Methylene blue abolishes aortal tone impairment induced by liver ischemia-reperfusion in a dose response manner: an isolated-perfused double-organ rat model study.
Liver ischemia-reperfusion (IR) generates remote organ reperfusion injury attributable to oxidative mediators. We tested the protective properties of methylene blue (MB) on aortal dysfunction. An ex vivo rat liver-aortal ring model was used to study the results of aortal exposure to post-ischemia (IR) hepatic effluent and its response to phenylephrine and isosorbide dinitrate in the absence or presence of increasing concentrations of MB in the effluent. Aortal incubation with IR effluents resulted in abnormal contraction. Ring's response to the vasoactive drugs was abnormally weak both during and following this exposure. Return to stabilization tone was irregular. MB (1.28 mM) best avoided overall dysfunction; 0.86 mM was partially effective, and 0.42 mM was ineffective. Nitrite/nitrate levels were similar to controls in the only IR 1.28 mM perfusate. Liver IR interferes with aortal tone and its response to vasoactive drugs, probably via oxidative interaction with nitric oxide. MB reverses these effects in a dose-dependent fashion.
Department of Anesthesiology and Critical Care, Tel Aviv Sourasky Medical Center, Tel Aviv University, Israel.
A A
AA
Weinbroum
Y
Y
Kluger
I
I
Shapira
V
V
Rudick
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D002316:Cardiotonic Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D007548:Isosorbide Dinitrate; D000109:Acetylcholine; D008751:Methylene Blue