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: D W Nelson, J M Brown, A Banerjee, D D Bensard, K B Rogers, C R Locke-Winter, B O Anderson, A H Harken
• Journal: Surgery (Surgery) Vol. 110 Issue 2 Pg. 365-9 (Aug 1991) ISSN: 0039-6060 [Print] United States
• PMID: 1858044 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antioxidants
• Lipid A
• Catalase
• monophosphoryl lipid A

Topics

• Analysis of Variance
• Animals
• Antioxidants
• Catalase (drug effects)
• In Vitro Techniques
• Lipid A (analogs & derivatives, therapeutic use)
• Male
• Myocardial Reperfusion Injury (physiopathology, prevention & control)
• Myocardium (enzymology)
• Rats
• Rats, Inbred Strains
• Time Factors
• Ventricular Function (drug effects)