Long-acting local anesthetics attenuate FMLP-induced acute lung injury in rats.
BACKGROUND
Endothelin-1 (ET-1) is a mediator of lung diseases and a potent pulmonary vasoconstrictor. In addition to thromboxane A2, it participates in the formation of lung edema. Both lidocaine and mepivacaine attenuate the increase of pulmonary arterial pressure (PAP) and lung edema development. We examined the effects of procaine, bupivacaine, and ropivacaine on experimentally evoked PAP increase and ET-1 release.


METHODS
PAP and lung weight were measured in isolated rat lungs during perfusion with Krebs-Henseleit hydroxyethyl starch buffer. Bupivacaine, ropivacaine, or procaine was added to the solution at concentrations of 10(-2)-10(-7) mg/kg. ET-1 levels were measured in the perfusate by enzyme-immunoassay, and thromboxane A2 levels were assayed by radioimmunoassay. N-formyl-L-leucine-methionyl-L-phenylalanine was used to activate human polymorphonuclear neutrophils.


RESULTS
Bupivacaine, ropivacaine, and procaine significantly attenuated increases of PAP (P < 0.05) and resulted in a reduction of lung weight in these treatment groups compared with the sham group (P < 0.05). The long-acting anesthetics bupivacaine and ropivacaine (P < 0.05), but not procaine, reduced ET-1 levels, produced low inflammation rates, and did not affect lung structures at doses from 10(-3) to 10(-6) mg/kg.


CONCLUSIONS
Bupivacaine and ropivacaine attenuated N-formyl-L-leucine-methionyl-L-phenylalanine-induced PAP, reduced lung edema, and diminished ET-1 release. Lidocaine and mepivacaine are more effective in reducing PAP and edema formation, but long-acting local anesthetics also inhibit ET-1 depletion and therefore have increased anti-inflammatory properties.
Schley
Marcus T
MT
Department of Anaesthesiology and Operative Intensive Care Medicine, Kantonsspital, Lucerne, Switzerland.
Casutt
Matthias
M
Haberthür
Christoph
C
Dusch
Martin
M
Rukwied
Roman
R
Schmelz
Martin
M
Schmeck
Joachim
J
Schüpfer
Guido K
GK
Konrad
Christoph J
CJ
D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy; D000577:Amides / Q000494:pharmacology; D000772:Anesthesia, Local / Q000379:methods; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002045:Bupivacaine / Q000494:pharmacology; D019332:Endothelin-1 / Q000096:biosynthesis; D005260:Female; D006098:Granulocytes / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008619:Mepivacaine / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D013928:Thromboxane A2 / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000577:Amides; D000893:Anti-Inflammatory Agents; D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000077212:Ropivacaine; D008012:Lidocaine; D008619:Mepivacaine; D002045:Bupivacaine