title: Pretreatment with a nontoxic derivative of endotoxin induces functional protection against cardiac ischemia/reperfusion injury.
abstract: We hypothesized that low-dose pretreatment of an intact animal with a nontoxic derivative of endotoxin, monophosphoryl lipid A (MPL), would induce protection against cardiac ischemia/reperfusion (I/R) injury. The purposes of this study were to investigate whether MPL pretreatment would induce functional protection against cardiac I/R injury, to delineate the temporal induction of protection, and to examine antioxidant enzyme induction as a mechanism of protection. Rats were administered a 5 mg/kg dose of MPL at 2 hours and 24 hours before a 25-minute, global, 37 degrees C ischemic insult followed by reperfusion (modified Langendorff). At 40 minutes of reperfusion, ventricular function was assessed (ventricular balloon; developed pressure, rate of contraction, rate of relaxation). Hearts from rats pretreated with MPL 24 hours before isolation exhibited preservation of ventricular function (p less than 0.05). After I/R, hearts from rats pretreated with MPL 24 hours before isolation had increased (p less than 0.05) catalase activity compared to saline pretreated controls and rats pretreated with MPL 2 hours before isolation. We conclude that (1) pretreatment with MPL induces functional protection against cardiac I/R injury, (2) protection (not evident at 2 hours) is maximal at 24 hours, suggesting enzyme induction, and (3) increased catalase activity correlates with the functional protection.
authors.affiliation: Department of Surgery, University of Colorado, Denver.
authors.forename: D W
authors.initials: DW
authors.lastname: Nelson
authors.forename: J M
authors.initials: JM
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: D D
authors.initials: DD
authors.lastname: Bensard
authors.forename: K B
authors.initials: KB
authors.lastname: Rogers
authors.forename: C R
authors.initials: CR
authors.lastname: Locke-Winter
authors.forename: B O
authors.initials: BO
authors.lastname: Anderson
authors.forename: A H
authors.initials: AH
authors.lastname: Harken
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants; D002374:Catalase / Q000187:drug effects; D066298:In Vitro Techniques; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D000975:Antioxidants; D008050:Lipid A; D002374:Catalase; C048436:monophosphoryl lipid A