title: Ropivacaine inhibits leukocyte rolling, adhesion and CD11b/CD18 expression.
abstract: Ropivacaine, a new local anesthetic, is currently being investigated for the treatment of ulcerative colitis, with promising results so far. The aim of this study was to examine anti-inflammatory properties of ropivacaine with regard to its effects on vascular permeability and inflammatory leukocyte behavior in vivo. The effects on leukocyte rolling, firm adhesion and vascular permeability were examined in the hamster cheek pouch microvasculature via intravital microscopy, and the effects on leukocyte adhesion molecules were examined in vitro by means of flow cytometry. In large venules, leukocyte adhesion induced by topical leukotriene B4 (LTB4) was almost completely inhibited during the combined application of ropivacaine and LTB4. The spontaneous rolling leukocyte flux was reduced by 72%, the rolling leukocyte fraction by 47% and the total leukocyte flux, which reflects blood flow, by 47%. In postcapillary venules, ropivacaine abolished rolling and LTB4-induced firm adhesion of leukocytes. LTB4 challenge also resulted in increased plasma exudation that was almost completely inhibited by ropivacaine. Moreover, ropivacaine inhibited the tumor necrosis factor alpha-induced up-regulation of CD11b/CD18 and L-selectin shedding by human leukocytes in vitro. Our results suggest that ropivacaine exerts anti-inflammatory activity, and this appears to be mediated to a significant extent by inhibition of both leukocyte rolling and adhesion.
authors.affiliation: Preclinical Research and Development, Astra Pain Control AB, Södertälje, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Martinsson
authors.forename: T
authors.initials: T
authors.lastname: Oda
authors.forename: E
authors.initials: E
authors.lastname: Fernvik
authors.forename: K
authors.initials: K
authors.lastname: Roempke
authors.forename: C J
authors.initials: CJ
authors.lastname: Dalsgaard
authors.forename: E
authors.initials: E
authors.lastname: Svensjö
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D018821:CD18 Antigens / Q000032:analysis*; D002118:Calcium / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D006224:Cricetinae; D006801:Humans; D019041:L-Selectin / Q000032:analysis; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000032:analysis*; D008297:Male; D008647:Mesocricetus; D000077212:Ropivacaine
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D019041:L-Selectin; D000077212:Ropivacaine; D002118:Calcium