The Effect of Lipopolysaccharide on Ischemic-Reperfusion Injury of Heart: A Double Hit Model of Myocardial Ischemia and Endotoxemia

Myocardial ischemia may coincide and interact with sepsis and inflammation. Our objective was to examine the effects of bacterial endotoxin on myocardial functions and cell injury during acute ischemia.Rabbits were pretreated with incremental doses of E. Coli lipopolysaccharide (LPS) or normal saline. Myocardial ischemia was induced by 50-minute occlusion of left anterior descending artery. S-TNFaR was additionally used to block the effects LPS.Ventricular contractility as it was measured by dp/dt during systole decreased from 2445± 1298 to 1422 ± 944 mm Hg/s, P = .019. Isovolumetric relaxation time as an index of diastolic function was prolonged from 50±18 ms to 102± 64 ms following ischemia. Pretreatment with low concentrations of LPS (<1 μg) had no effect on dp/dt, while at higher concentrations it suppressed both contractility and prolonged IVRT. Cell injury as measured by cardiac troponin I level increased to 15.1± 3.2 ng/dL following ischemia and continued to rise with higher doses of LPS. While blocking TNFa did not improve the myocardial contractility after ischemia, it eliminated additional deleterious effects of LPS.Lower doses of LPS had no deleterious effect on myocardial function, whereas higher doses of this endotoxin cause cardiac dysfunction and increased extent of injury.