Effects of five amino–amide local anaesthetic agents on human polymorphonuclear leukocytes measured by chemiluminescence

Abstract

The aim of this study was to assess the influence of five amino-amide local anesthetic agents on the production of oxygen metabolites in the human polymorphonuclear leukocyte (PMNL), both intra- and extracellularly. Ropivacaine, a new long-acting amino-amide local anaesthetic agent, bupivacaine, lidocaine, mepivacaine and prilocaine in concentrations 1-5 micrograms.ml-1 up to 500-1000 micrograms.ml-1 were compared to an untreated control. PMNLs were isolated from heparinized blood (healthy adult volunteers). Cells were incubated with the various local anaesthetics (37 degrees C, 30 min), then placed in a Biolumat (luminol-amplified chemiluminescence) and stimulated by formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol myristate acetate (PMA) or ionomycin. Horseradish peroxidase (HRP) was added to discriminate between an intra- or extracellular response. In general, a decrease in chemiluminescence-response was seen with higher concentrations (500-1000 micrograms.ml-1) of the various local anaesthetics. Lidocaine showed a decrease even at lower concentrations. A marked increase in intracellular response for prilocaine 1000 micrograms.ml-1 (3894 mumol.l-1) accompanied by a reduction in extracellular response, using FMLP +/- HRP as a stimuli, was noted. Ropivacaine 1000 micrograms.ml-1 (3216 mumol-l-1) showed a decrease both intra- and extracellularly that was similar to, and even somewhat more pronounced than lidocaine 1000 micrograms.ml-1 (3692 mumol.l-1), when using PMA with or without HRP as the stimuli.

Effects of ropivacaine on eicosanoid release from human granulocytes and endothelial cells in vitro

“…Ropivacaine has also been found to exert protective effects in a rat colitis model (T. Martinsson, unpublished observation) and, as assessed using human neutrophils in vitro, to inhibit formation of reactive oxygen metabolites [18] as well as adhesion and expression of adhesion molecules [19]. These observations are in line with several previous studies indicating anti-inflammatory effects of local anesthetics other than ropivacaine [20][21][22][23][24][25][26].…”

Effects of Lidocaine on Cytosolic pH Regulation and Stimulus-Induced Effector Functions in Alveolar Macrophages

“…Lidocaine has been shown previously to inhibit a variety of the stimulus-induced effector functions of leukocytes, including superoxide production, release of granule lysozyme and myeloperoxidase, and production of leukotriene B 4 and interleukin-1 [7,11,24,25]. In keeping with these findings, lidocaine significantly suppressed PMAinduced superoxide production in rabbit alveolar m. These actions of lidocaine are probably mediated through effects on cytoplasmic second messenger systems.…”

“…The findings of these in vivo studies are generally consistent with what is known of the effect of lidocaine on leukocytes in vitro. Lidocaine suppresses a number of leukocyte effector functions in vitro, including the respiratory burst, phagocytosis, inflammatory mediator release, and cell degranulation [7,8,11,[23][24][25]. The local anesthetic may also interfere with leukocyte housekeeping (homeostatic) functions, including intracellular pH (pH i ) regulation.…”

Leukocyte hydrogen peroxide production in a surgical wound in mice. The effects of an amide local anaesthetic

“…Lidocaine may also inhibit (via an unknown pathway) molecular interactions between immunoreactants and the surface of the leukocyte, leading to failed microtubular/microfilament changes and subsequent reduced superoxide anion production and failed occurrence of intracellular enzymes (11) at the inflammatory site. As a result, this can possibly decrease concentrations of known biologically active agents (4,15), including oxygen metabolites (16). In an earlier study, with topical lidocaine treatment in higher dosage, we found a decreased number of leukocytes in the inflammatory exudate during the first three days postoper-atively (13).…”

“…Apart from studies using chemiluminescence (CL) (13,16), few details are known about the interactions of amide local anaesthetics with leukocyte oxygen metabolism in vivo. The major aim of the present study was therefore to investigate the effect of lidocaine on the production of H202, a relatively stable and potentially harmful metabolite of the leukocyte oxygen metabolism, at two different times in the surgical wound healing process.…”