title: Preconditioning with monophosphoryl lipid A improves survival of critically ischemic tissue.
abstract: In this study we sought to assess the effects of preconditioning with monophosphoryl lipid A on critically ischemic wound margins and on systemic and local hemodynamics and oxygenation during prolonged anesthesia with volatile anesthetics and narcotics. Twenty large white pigs were randomly assigned to receive either monophosphoryl lipid A 35 mug/kg IV or saline 24 h before dissection of a buttock flap. The animals were anesthetized with isoflurane (end-tidal concentration approximately 1.25%) for surgery and subsequent monitoring of hemodynamics and oxygenation both systemically and in the flap tissue for 6 h. Preconditioning resulted in increased cardiac index and oxygen delivery (both P < 0.05) and in decreased central venous pressure and systemic vascular resistance (both P < 0.01). In the preconditioned flap tissue, microcirculatory blood flow (laser Doppler flowmetry) and partial tissue oxygen tension (polarographic microprobes) were up to 2.5-fold higher compared with control (both P < 0.05) and flap necrosis was reduced by 20% on postoperative day 14 (P < 0.05). Our results suggest that preconditioning with a single dose of monophosphoryl lipid A may attenuate ischemia-related wound healing complications, which may be related to an improvement in perfusion and oxygenation of this tissue. Furthermore, preconditioning exerted a systemic cardiovascular stabilization effect during prolonged isoflurane anesthesia.
authors.affiliation: From the Department of Plastic Surgery and the Surgical Research Unit, Inselspital University Hospital, Berne, Switzerland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Harder
authors.forename: Claudio
authors.initials: C
authors.lastname: Contaldo
authors.forename: Joachim
authors.initials: J
authors.lastname: Klenk
authors.forename: Andrej
authors.initials: A
authors.lastname: Banic
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Jakob
authors.forename: Dominique
authors.initials: D
authors.lastname: Erni
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D001784:Blood Gas Analysis; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D017078:Laser-Doppler Flowmetry; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D013524:Surgical Flaps; D013552:Swine
chemical_list: D008050:Lipid A; C048436:monophosphoryl lipid A