Reduction of pulmonary edema by short-acting local anesthetics.
OBJECTIVE
Local anesthetics (LAs) possess a variety of effects that cannot be explained by the typical block of neuronal sodium channels. Antithrombotic effects of LAs are well known, but LAs also act as bactericides. Therefore, an investigation of the influence of LAs on the inflammatory response of the isolated rat lung (n = 78) to an N-formyl-l-leucin-methionyl-l-phenylalanine (FMLP) stimulus was performed.


METHODS
The experiments were performed on isolated and ventilated rat lungs perfused with cell-free and plasma-free buffer. LAs (lidocaine and mepivacaine) were injected in various concentrations before application and activation of human granulocytes by FMLP. Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. LAs in final dosages from 10(-2) to 10(-7) mg/kg body weight (n = 6 each) were injected into the pulmonary artery before treatment with FMLP (10(-6) M) to induce pulmonary arterial hypertension. Perfusate samples were taken intermittently to determine thromboxane A(2) (TX A(2)) and endothelin-1 concentrations. Microscopic analyses were performed to assess the degree of lung injury.


RESULTS
Pretreatment with LAs significantly reduced the FMLP-induced PAP increase (treatment group v sham group: 0.5 to 5 mm Hg v 8 mm Hg; P < .05) and the release of endothelin-1 (2.4 v 5 fmol/mL). Histologic damage seen as acute granulocytic alveolitis was reduced by lidocaine and mepivacaine, even below clinically relevant concentrations.


CONCLUSIONS
LA pretreatment reduces inflammatory reactions after FMLP stimulus.
Konrad
Christoph J
CJ
Department of Anesthesiology and Operative Intensive Care Medicine, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany. christoph.konrad@anaes.ma.uni-heidelberg.de
Schuepfer
Guido K
GK
Neuburger
Michael
M
Schley
Marcus
M
Schmelz
Martin
M
Schmeck
Joachim
J
D000779:Anesthetics, Local / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008619:Mepivacaine / Q000494:pharmacology / Q000627:therapeutic use; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009929:Organ Size; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000779:Anesthetics, Local; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008012:Lidocaine; D008619:Mepivacaine