title: Impact of methylene blue in addition to norepinephrine on the intestinal microcirculation in experimental septic shock.
abstract: Methylene blue (MB) has been used with some success as a treatment for the vasoplegia of vasopressor-refractory septic shock. The putative mechanism of action of MB is the inhibition of endothelial nitric oxide within the microvasculature and improved responsiveness to endogenous catecholamines (norepinephrine (NE)). However, to date, no study has demonstrated the microcirculatory effect of methylene blue in septic shock. The objective of this randomized, controlled, animal study was to show, in an experimentally-induced, septic shock model in rats, the effects of MB and NE on global hemodynamics and the microcirculation. Mean arterial pressure (MAP) was drastically reduced following bacterial endotoxin (lipopolysaccharide, LPS) administration in animals not receiving vasopressors. Only the combination of NE + MB restored MAP to control levels by the end of the three hour experiment. Intravital microscopy of the microcirculation was performed in the terminal ileum in order to examine functional capillary density in intestinal muscle layers and the mucosa, as well as leukocyte activation in venules (rolling, adhesion to the endothelium). Untreated LPS animals showed a significant increase in leukocyte adhesion and a decrease in capillary perfusion in the intestinal microcirculation. In groups receiving NE or NE+MB, we observed a significant decrease in leukocyte adhesion and improved functional capillary density, indicating that microvasculature function was improved. This study suggests that methylene blue may be able to improve hemodynamics while preserving microvascular function in septic shock.
authors.affiliation: Department of General Surgery, Dalhousie University, Halifax, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Nantais
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Canada.
authors.forename: Tristan C
authors.initials: TC
authors.lastname: Dumbarton
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Canada Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada.
authors.forename: Nizam
authors.initials: N
authors.lastname: Farah
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Canada Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Maxan
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Canada Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Dalhousie University, Halifax, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Minor
authors.affiliation: Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, Canada Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada Deparment of Pharmacology, Dalhousie University, Halifax, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D004731:Endotoxins / Q000737:chemistry; D006439:Hemodynamics; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects*; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry; D008751:Methylene Blue / Q000737:chemistry*; D008833:Microcirculation / Q000187:drug effects*; D009638:Norepinephrine / Q000737:chemistry*; D011312:Pressure; D051381:Rats; D011917:Rats, Inbred Lew; D012772:Shock, Septic / Q000503:physiopathology*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D008751:Methylene Blue; D009638:Norepinephrine
keywords: Methylene blue; intravital imaging; microcirculation; norepinephrine; septic shock