Abstract
Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.
Highlights
Myocardial ischemia may coincide and interact with sepsis and inflammation
In comparison to SHAM control with a shortening percentage of 12 ± 2.6%, the anterior ventricular wall segment shortening disappeared during systole and there was a systolic lengthening of 5.3 ± 1.2% after ischemia was induced (Wall dyskinesia)
The dyskinesia of the anterior ventricular wall (-5.3 ± 1.2%) due to ischemia improved to akinesia or hypokinesia of the ischemic wall at 0.1 ± 1.5% (P < .001) when ischemic hearts were treated with low doses of LPS (
Summary
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. Conclusion: 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. While low dose TNFα improved the systolic function of the heart, the higher doses of this cytokine suppressed myocardial contractility and increased myoglobin leak from an ex vivo model of functioning heart following ischemia.[8] We have shown that TNFα is an important inflammatory cytokine, which is released in response to myocardial ischemia in human models.[9] In this study the dose-response effects of the E. Coli endotoxin lipopolysaccharide (LPS) on ischemic hearts during reperfusion has been assessed Intravenous injections of this endotoxin have been associated with dose response release of TNFα in a rabbit model of injury.[10] We have tested the hypothesis that LPS is deleterious to the recovery of myocardium following an ischemia-reperfusion insult. The decision to use LPS rather than the rodent model of sepsis was to fo-
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