Preconditioning with Monophosphoryl Lipid A Improves Survival of Critically Ischemic Tissue

Abstract

In Brief 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 μg/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. IMPLICATIONS: In pigs, a single dose of monophosphoryl lipid A given one day before surgery stabilized systemic hemodynamics and oxygen delivery during 9 h of anesthesia with a volatile anesthetic. Furthermore, the long-time survival of critically ischemic wound margins was improved.