Impact of methylene blue in addition to norepinephrine on the intestinal microcirculation in experimental septic shock
Issue title: Selected Presentations held at the 33th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology, Villingen-Schwenningen, Germany, 14-15 November, 2014
Affiliations: Department of General Surgery, Dalhousie University, Halifax, Canada | 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
Note: [] Corresponding author: Christian Lehmann, Department of Anesthesia, Pain Management and Perioperative Medicine, QE II Health Sciences Centre, 10 West Victoria, 1276 South Park Street, Halifax, NS, B3H 2Y9, Canada. Tel.: +1 902 494 1287; Fax: +1 902 473 1035; E-mail: chlehmann@dal.ca
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.
